Category IX: Clinical Research

November 2023 Vol 14, No 11 —November 22, 2023

A1 Additional Practice-informing Adverse Event Patterns and Management in the KRYSTAL-1 Phase 2 Study of Adagrasib (MRTX849) in Patients With KRASG12C-mutated Non–Small Cell Lung Cancer

Jun Zhang, MD, PhD1; Konstantinos Leventakos, MD, PhD2; Ticiana A. Leal, MD3; Nathan A. Pennell, MD, PhD4; Minal Barve, MD5; Scott Paulson, MD6; Lyudmila Bazhenova, MD7; Melissa L. Johnson, MD8; Richard C. Chao, MD9; Karen Velastegui, BSc9; Chunlin Qian, PhD9; Alexander Spira, MD, PhD10

1University of Kansas Medical Center, Kansas City, KS; 2The Mayo Clinic, Rochester, MN; 3Winship Cancer Institute, Emory University, Atlanta, GA; 4The Cleveland Clinic, Cleveland, OH; 5Mary Crowley Cancer Research Center, Dallas, TX; 6Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas, TX; 7UC San Diego Moores Cancer Center, La Jolla, CA; 8Sarah Cannon Research Institute at Tennessee Oncology, Nashville, TN; 9Mirati Therapeutics, Inc, San Diego, CA; 10Virginia Cancer Specialists, Fairfax, VA, and US Oncology Research, The Woodlands, TX

Background: Adagrasib, a KRASG12C inhibitor selected for favorable properties, including a long half-life (23 hr), dose-dependent pharmacokinetics, and central nervous system (CNS) penetration, has demonstrated clinical activity in patients with KRASG12C-mutated non–small cell lung cancer (NSCLC) with an objective response rate (ORR) of 43% and a median overall survival of 12.6 months, including patients with CNS metastases (intracranial ORR per modified response assessment in neuro-oncology brain metastases, 33%).

Objective: To report additional practice-informing safety analyses from KRYSTAL-1 cohort A, a registrational phase 2 cohort, evaluating adagrasib capsules 600 mg orally twice daily in patients with previously treated NSCLC.

Methods: KRYSTAL-1 is a multicohort phase 1/2 study of adagrasib in patients with advanced solid tumors harboring a KRASG12C mutation. Analyses reported here include time to onset (TTO), time to resolution (TTR), and the management of treatment-related adverse events (TRAEs), including gastrointestinal (GI)-related TRAEs.

Results: As of October 15, 2021, 116 patients (female, 56%; median age, 64 y; Eastern Cooperative Oncology Group performance status 1, 84%) received adagrasib; median follow-up was 12.9 months (95% CI, 11.8-13.5), and median treatment duration was 5.7 months (range, 0-19.6 mo). Any grade TRAEs occurred in 97% of patients: grade 1-2, 53%; grade ≥3, 45%. Overall, >92% of new-onset TRAEs occurred within the first 3 cycles; few new grade ≥3 TRAEs occurred after cycle 3. TRAEs led to dose reduction, interruption, and discontinuation in 52%, 61%, and 7% of patients, respectively. GI-related TRAEs occurred in 85%, leading to dose reductions in 20%. Median TTO of GI TRAEs was 3 days (interquartile range, 1-12 d) and of increased alanine transaminase/aspartate aminotransferase levels was 22 days (interquartile range, 15-35 d); median TTR of these TRAEs after initial occurrence was 14 days (range, 5-43 d) and 12 days (range, 7-21 d), respectively. GI TRAEs were manageable with antidiarrheals (48%) and antiemetics/antinauseants (87%).

Conclusions: Adagrasib demonstrated a manageable adverse event profile in pretreated patients with KRASG12C-mutated NSCLC. Most TRAEs were low grade, occurred early in treatment, and resolved quickly, resulting in a low (7%) discontinuation rate.

Funding: This study (NCT03785249) was sponsored by Mirati Therapeutics, Inc. Third-party medical writing support, under the direction of the authors, was provided by Hannah Preston, BSc, of Ashfield MedComms, an Inizio company, and was funded by Mirati Therapeutics, Inc.

This abstract was previously presented at the European Society for Medical Oncology (ESMO) Conference 2022; Final Publication Number: 1133P. The study was previously published in Zhang J, et al. Annals Oncol. 2022;33(suppl 7):S1068-S1069. doi: 2022. 07.1257. Data previously published in Zhang J, Johnson M, Barve M, et al. Oncologist. 2023;28(4):287-296. Reused with permission.

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A2 Compassionate Connection: Evaluating Patient Satisfaction With Oncology Nurse Navigation in Pancreatic Multidisciplinary Cancer Care

Liliana Larsson, MSN, RN, OCN, CCRP, TTS; Matthew Katz, MD; Brandon Smaglo, MD; Anirban Maitra, MBBS

The University of Texas MD Anderson Cancer Center, Houston, TX

Background: Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) are likely to experience changes in their routines and roles, and face multiple decisions in a very short time, creating overwhelming distress and hindering their ability to engage in decision-making and to adopt coping mechanisms, which may affect their satisfaction with care. Navigation increases patients’ quality of life, satisfaction with care, and care experience. Patients using nurse navigators have reported fewer issues accessing different aspects of treatment, psychosocial care, care coordination, and information.

Objectives: To evaluate the level of satisfaction among patients diagnosed with PDAC regarding the implementation of an innovative nursing navigation service within the pancreatic clinic at a large academic cancer center. By examining patient feedback and perceptions, this study aims to determine the effectiveness and impact of these newly introduced navigation services on patient satisfaction.

Methods: New patients in the pancreatic clinic with a PDAC diagnosis were approached by a nurse navigator during their first visit, within 7 days, and as needed, to assess their level of distress and perceived barriers to care. The navigator utilized a standardized approach to assess and anticipate the patients’ needs, provide a point of contact, identify resources, and educate and orient patients about the immediate steps in their continuum of care. Based on the assessment, the navigator shared appropriate resources and guidance, initiated referrals, and continued following up with the patients through their treatment into survivorship or transfer of care. To assess satisfaction with care and services, the patients received an 8-question survey 7 days after their first encounter with the navigator. The participants were informed that their responses would be anonymous to ensure confidentiality and privacy.

Results: A total of 473 patients were navigated between May 2022 and April 2023. The survey was completed by 92 patients. Of these, 89 patients (96.8%) reported being very satisfied/satisfied with the knowledge of the navigator about their case; 88 patients (95.6%) felt the navigator provided them with useful information; 87 patients (94.5%) reported they felt the navigator kept them informed; 88 patients (95.6%) would recommend the navigator services to others; and 84 patients (91.3%) reported the navigator services improved their overall experience with care.

Conclusions: Navigation programs provide the opportunity for nursing practice to elevate patient care by addressing barriers to care and having anticipatory educational conversations regarding treatment and services that decrease distress levels and increase comfort for patients and caregivers. Patients feel supported knowing they have an available point of contact or “compass” during their treatment journey and transitions, positively impacting their satisfaction with care. Early educational sessions provide a foundation and encourage patients to take an active role in making informed decisions about their treatment, improving adherence while decreasing their emotional burden. Large academic institutions should explore incorporating nurse navigators in specialized clinics, such as the PDAC clinic, to address the unique needs of this patient population. These findings will contribute valuable insights into the role of nursing navigation in enhancing the patient experience and improving care delivery in PDAC management, ultimately guiding the development of comprehensive and patient-centered approaches.


Chillakunnel Hussain Rawther S, Pai MS, Fernandes DJ, et al. A randomized controlled trial to evaluate the impact of a nurse navigator programme on outcomes of people with breast cancer: study protocol. J Adv Nurs. 2017;73(4):977-988. Accessed June 14, 2023.

Clark KL, Loscalzo M, Trask PC, Zabora J, Philip EJ. Psychological distress in patients with pancreatic cancer–an understudied group. Psychooncology. 2010;19 (12):1313-1320. Accessed June 14, 2023.

Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clinicians. 2021;71(3):209-249. Accessed June 14, 2023.

Wong SS, George TJ Jr, Godfrey M, Le J, Pereira DB. Using photography to explore psychological distress in patients with pancreatic cancer and their caregivers: a qualitative study. Support Care Cancer. 2019;27(1):321-328. Accessed June 14, 2023.

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A3 ctDNA Dynamics, Prognostic Markers, and Mechanisms of Resistance in Tepotinib-treated MET exon 14 (METex14) Skipping NSCLC in the VISION Trial

Xiuning Le1; Marina Chiara Garassino2,3; Myung-Ju Ahn4; Enriqueta Felip5; Alexis B. Cortot6; Hiroshi Sakai7,8; Julien Mazières9; Michael Thomas10; Santiago Viteri11,12; Pierfranco Conte13; James Chih-Hsin Yang14; Wade Thomas Iams15; Frank Griesinger16; Danielle Braggio17; Christopher Stroh18; Dilafruz Juraeva18; Danyi Wang17; Andreas Johne18; Paul K. Paik19

1The University of Texas MD Anderson Cancer Center, Houston, TX; 2Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 3Knapp Center for Biomedical Discovery, The University of Chicago, Chicago, IL; 4Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 5Vall d’Hebron Institute of Oncology, Barcelona, Spain; 6Univ. Lille, CHU Lille, Institut Pasteur de Lille, Lille, France; 7Saitama Cancer Center, Kitaadachi-gun, Japan; 8Ageo Central General Hospital, Saitama, Japan; 9CHU de Toulouse, Université Paul Sabatier, Toulouse, France; 10Thoraxklinik and National Center for Tumor Diseases, Heidelberg University Hospital; Translational Lung Research Center, Heidelberg, Germany; 11UOMI Cancer Center, Clínica Mi NovAliança, Lleida, Spain; 12Dr Rosell Oncology Institute, Dexeus University Hospital, QuironSalud Group, Barcelona, Spain; 13University of Padova and Oncologia Medica 2, Istituto Oncologico Veneto, IRCCS, Padova, Italy; 14National Taiwan University Cancer Center, Taipei, Taiwan; 15Vanderbilt University Medical Center, Nashville, TN; 16Pius-Hospital, University Medicine Oldenburg, Oldenburg, Germany; 17EMD Serono, Billerica, MA; 18Merck KGaA, Darmstadt, Germany; 19Memorial Sloan-Kettering Cancer Center, New York, NY

Background: Oncology nurse navigators are integral members of multidisciplinary teams that manage patients with non–small cell lung cancer (NSCLC), including the 3%-4% of patients with mesenchymal-epithelial transition exon 14 (METex14) skipping mutation. This oncogenic driver confers a poor prognosis but sensitizes tumors to MET inhibitors. Tepotinib, an oral, selective MET inhibitor, showed robust, durable efficacy in METex14 NSCLC in the VISION trial.

Objective: To support nurse navigators and other professionals managing these patients, we conducted an exploratory analysis of VISION to evaluate circulating tumor DNA (ctDNA) and MET-related biomarkers in liquid biopsy (LBx [ie, blood]) samples and their associations with clinical outcomes.

Methods: Baseline, on-treatment and/or end-of-treatment (EOT) LBx from VISION were analyzed by ctDNA next-generation sequencing (NGS; Guardant360®) and enzyme-linked immunoassay for shed MET (sMET; a soluble form of the MET extracellular domain) and hepatocyte growth factor (HGF; the ligand for MET). Patients with baseline LBx NGS profiles (n=165) were classified as positive (L+) or negative (L-) for METex14 (all L- patients had METex14 by tissue NGS). On-treatment response was analyzed in L+ patients with 2 consecutive on-treatment samples (n=81). Confirmed molecular response (cMR) was defined as >75% depletion from baseline in METex14 variant allele frequency (VAF) in 2 consecutive on-treatment samples; molecular progression (MP) was defined as VAF increase from baseline in ≥1 on-treatment sample. Objective response rate (ORR), median duration of response (mDOR), median progression-free survival (mPFS), and median overall survival (mOS) were evaluated according to biomarker status. Mechanisms of acquired resistance were investigated in postprogression EOT samples. Data cut-off date was November 20, 2022.

Results: Patients with high (>upper quartile, n=58) versus low (≤upper quartile, n=175) baseline HGF had numerically shorter mDOR and mPFS. Patients with low (≤lower quartile, n=61) versus high (>lower quartile, n=183) relative change in sMET from baseline had numerically higher ORR, mPFS, and mOS. In L- (n=51) versus L+ (n=114) patients, ORR was comparable, but mDOR and mPFS were longer. Seven of 10 patients with MET amplification, 1 of 5 patients with KRAS/NRAS mutation, 1 of 5 patients with PI3K/AKT pathway alterations, and 0 of 2 patients with EGFR mutations at baseline had objective response. Patients with tumor protein 53 (TP53) mutations (73/165) versus wild-type had comparable ORR but shorter mPFS (8.2 vs 11.3 mo, respectively). Patients with cMR (n=65 [80%]) versus MP (n=12 [15%]) had better outcomes (ORR: 63.1% vs 16.7%, respectively; mDOR: 18.5 vs 6.2 mo, respectively; mPFS: 11.2 vs 4.2 mo, respectively). At EOT, 9 of 73 patients (12%) had acquired MET kinase domain mutations and 9 of 73 (12%) had emerging alterations in KRAS, EGFR, MYC, BRAF, RB1, and ERBB2.

Conclusions: In the largest on-treatment LBx biomarker dataset for an MET inhibitor in METex14 NSCLC, MR was associated with improved outcomes and TP53 mutation had negative prognostic significance. On-target secondary MET mutations and off-target bypass pathway activation were potential resistance mechanisms. These data can help to inform nurse navigators and other healthcare professionals managing patients receiving tepotinib for METex14 skipping NSCLC.

Funding: This study was funded by Merck KGaA, Darmstadt, Germany.

This abstract was previously submitted to the 2023 World Conference on Lung Cancer.

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A4 Cutaneous Toxicities With Amivantamab for Non–Small Cell Lung Cancer (NSCLC) With Exon 20 Insertion Mutation (ex20ins): A Practical Guide and Best Practices for Management

Shahnaz Singh-Kandah, NP1; Kaiwen Wang, PharmD2; Karen Xia, PhD3; Andy L. Johnson, DPhil3; Denise D’Andrea, MD3; Lindsay Dougherty, CRNP, DNP4

1Columbia University, New York, NY; 2MD Anderson Cancer Center, Houston, TX; 3Janssen Scientific Affairs, LLC, Horsham, PA; 4University of Pennsylvania, Philadelphia, PA

Background: Amivantamab, a monoclonal epidermal growth factor receptor (EGFR)-mesenchymal–epithelial transition factor bispecific antibody, is an approved treatment for patients with ex20ins advanced NSCLC after platinum-based chemotherapy. Cutaneous toxicities including rash and paronychia are known on-target effects of EGFR inhibition. Rash is a grouped term for various types of skin inflammation that can occur during treatment with amivantamab.

Objective: To present data from the CHRYSALIS trial on the incidence, severity, time to first onset, and management of rash and paronychia in patients treated with amivantamab.

Methods: This post hoc analysis evaluated incidence, severity, and time to first onset of rash and paronychia with descriptive summary statistics (mean, median, interquartile range, range).

Results: In patients receiving amivantamab in CHRYSALIS ([N=380]; data cutoff March 2021, with 9.9-mo median follow-up), rash and paronychia were reported in 75.8% (grade 3: 2.9%) and 43.2% (grade 3: 1.8%), respectively. No grade 4 events occurred. Median time to first onset of rash and paronychia was 14 days and 67 days, respectively. Rash and paronychia infrequently required treatment modifications (dose reductions: 5.5% and 2.6%, respectively; treatment discontinuation: 0.3% and 0.5% of patients, respectively). To mitigate rash, patients received ≥1 treatment, including topical or systemic antibiotics (13.2%, 64.9%, respectively), topical or systemic corticosteroids (41.3%, 45.8%, respectively), emollients (8.0%), anti-acne preparations (5.9%), and others. Preventive measures include referring patients to a dermatologist, minimizing sun exposure, and administering antibiotics. Rash may be mitigated with methods to prevent dry skin and nail bed infections, and with topical treatments. Treatment can be escalated to oral antibiotics and/or systemic steroids when necessary. Scalp rashes are managed differently with various topical treatments.

Conclusions: Nurses and advanced practice providers (APPs) offer comprehensive support and play critical roles in the education of patients and caregivers in the prevention and management of cutaneous toxicities. Rash and paronychia can cause physical discomfort and emotional distress for patients. However, these may not be prioritized by patients among other concerns regarding their cancer treatment. In summary, cutaneous toxicities are commonly observed adverse events with EGFR inhibitors including amivantamab and can be effectively managed with the support and guidance of nurses and APPs throughout the treatment journey.

Funding: This study was funded by Janssen Research & Development, LLC.

This abstract was previously submitted to the Oncology Nursing Society (ONS) 2023, Canadian Association of Nurses in Oncology (CANO) 2023, and the European Academy of Dermatology and Venerology (EADV) 2023.

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A5 Cytochrome P450–inhibiting/inducing Medication Use Among Patients With Advanced Ovarian Cancer (aOC) Who Received or Were Eligible for Poly(ADP-ribose) Polymerase Inhibitors (PARPis) as First-line Maintenance Therapy

Bobbie J. Rimel, MD1; Dana Chase, MD2; Jessica Perhanidis, MPH3; Armen A. Ghazarian, PhD4; Ella Xiaoyan Du, MSc5; Travis Wang, MSc5; Jinlin Song, PhD5; Amanda K. Golembesky, PhD6; Jean A. Hurteau, MD3; Ritu Salani, MD7; Bradley J. Monk, MD8

1Cedars-Sinai Medical Center, Los Angeles, CA; 2Arizona Center for Cancer Care, Phoenix, AZ, at the time the analysis was conducted; currently at David Geffen School of Medicine at UCLA, Los Angeles, CA; 3GSK, Waltham, MA; 4GSK, Washington, DC, at the time the analysis was conducted; currently at Daiichi Sankyo, Inc; 5Analysis Group, Los Angeles, CA; 6GSK, Durham, NC; 7David Geffen School of Medicine at UCLA, Los Angeles, CA; 8HonorHealth Research Institute, University of Arizona, Creighton University, Phoenix, AZ

Background: As a class, PARPis work by disrupting DNA repair; however, they are metabolized by different pathways. Niraparib is metabolized by carboxylesterase-catalyzed amide hydrolysis, whereas olaparib and rucaparib are metabolized by the cytochrome P450 (CYP) system. Drug-drug interactions (DDIs) with other medications may change PARPi efficacy or safety in patients with aOC.

Objective: This US-based, real-world study aimed to quantify and characterize patients with aOC who received CYP-inhibiting/inducing (CYP-i/i) medications when they initiated treatment or were eligible to receive PARPi first-line maintenance therapy (1LMT), to better understand the potential for DDIs with PARPis and other CYP-metabolized medications.

Methods: This retrospective cohort study used data from Optum’s de-identified Market Clarity Data with Optum® Enriched Oncology, which deterministically links medical and pharmacy claims with electronic health record data from providers across the continuum of care. Eligible patients were diagnosed with aOC between January 1, 2015, and March 31, 2021; were aged ≥18 years at end of first-line platinum-based chemotherapy (index date); had confirmed CYP-i/i medication use (≥1 claim between 90 days before to 120 days after index date); and had received or were eligible to receive PARPi 1LMT. Strong/moderate CYP-i/i medications were defined based on estimates of how much they increased/decreased drug exposure over time (area under the plasma concentration–time curve ratio). Patients in the PARPi-treated group received PARPi monotherapy for 1LMT (olaparib/rucaparib/niraparib). Patients in the PARPi-eligible group did not receive 1LMT within 120 days or start second-line treatment within 60 days of the index date. Descriptive statistics were used for patient characteristics.

Results: The analysis included 1411 patients (PARPi treated, n=158; PARPi eligible, n=1253). Median age was 63 years for PARPi-treated patients and 64 years for PARPi-eligible patients. Among PARPi-treated patients, 46% (n=73) used niraparib, and 54% (n=85) used other PARPis metabolized by the CYP system (olaparib, 49% [n=77]; rucaparib, 5% [n=8]). The percentage of patients taking a strong/moderate CYP-i/i medication was 38% (n=60) for the overall PARPi-treated group, 42% (n=36) for PARPi-treated patients who received olaparib or rucaparib, and 33% (n=414) for the PARPi-eligible group. For each group, the most common strong/moderate CYP-i/i medications were antiemetics and fluoroquinolone antibiotics (overall PARPi treated, 48% [n=29] and 28% [n=17], respectively; PARPi-treated olaparib/rucaparib, 50% [n=18] and 25% [n=9], respectively; and PARPi eligible, 41% [n=169] and 37% [n=154], respectively). Other common strong/moderate CYP-i/i medications were imidazole-related antifungals, calcium channel–blocking blood pressure medications, and topical antifungals.

Conclusions: Patients with aOC may be treated with PARPi 1LMT to delay or prevent recurrence. Multiple PARPi options exist, including niraparib, which is metabolized by carboxylesterase-catalyzed amide hydrolysis, and olaparib and rucaparib, which are metabolized by the CYP system. In this analysis, 38% of PARPi-treated and 33% of PARPi-eligible patients with aOC also received medications that were strong/moderate CYP-i/i. Cotreatment with CYP-metabolized PARPis and CYP-i/i medications could potentially lead to DDIs that could alter the efficacy and tolerability of the PARPis. Additional studies are needed to understand this important issue.

Funding: Funding for this study was provided by GSK.

This abstract was previously submitted to the Society of Gynecologic Oncology 2023 Annual Meeting.

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A6 Glofitamab in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma and ≥2 Prior Therapies: Results From a Pivotal Phase 2 Expansion Study

Michael Dickinson, MBBS, DMedSc1; Carmelo Carlo-Stella, MD2; Franck Morschhauser, MD, PhD3; Emmanuel Bachy, MD, PhD4; Paolo Corradini, MD5; Gloria Iacoboni, MD6; Cyrus Khan, MD7; Thomasz Wróbel, MD8; Fritz Offner, MD, PhD9; Marek Trněný, MD10; Shang-Ju Wu, MD, PhD11; Guillaume Cartron, MD, PhD12; Mark Hertzberg, MBBS, PhD13; Anna Sureda, MD, PhD14; David Perez-Callejo, PhD15; Linda Lundberg, PhD15; James Relf, MD16; Emma Clark, MSc16; Kathryn Humphrey, BSc16; Martin Hutchings, MD, PhD17

1Peter MacCallum Cancer Centre, Royal Melbourne Hospital and the University of Melbourne, Melbourne, Australia; 2Humanitas University and Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Humanitas Research Hospital, Milan, Italy; 3Hôpital Claude Huriez and CHU de Lille, Lille, France; 4Centre Hospitalier Lyon-Sud, Lyon, France; 5Università degli Studi di Milano and Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; 6Vall d’Hebron University Hospital, Barcelona, Spain; 7Allegheny Health Network, Pittsburgh, PA; 8Uniwersytet Medyczny we Wrocławiu, Wroclaw, Poland; 9Universitair Ziekenhuis Gent, Ghent, Belgium; 10Charles University Hospital, Prague, Czech Republic; 11National Taiwan University Hospital, Taipei, Taiwan; 12CHU de Montpellier, Montpellier, France; 13Prince of Wales Hospital and University of New South Wales, Sydney, Australia; 14Institut Català d'Oncologia Hospitalet, Barcelona, Spain; 15F. Hoffmann-La Roche Ltd, Basel, Switzerland; 16Roche Products Ltd, Welwyn Garden City, UK; 17Rigshospitalet, Copenhagen, Denmark

Background: Glofitamab is a CD20xCD3 bispecific antibody with a novel 2:1 configuration. In a phase 1/2 study (NCT03075696), escalating doses of glofitamab were highly active and well tolerated in patients with relapsed/refractory (R/R) B-cell lymphomas.

Objective: To present results for the pivotal phase 2 expansion study of glofitamab in patients with R/R diffuse large B-cell lymphoma (DLBCL) and ≥2 prior therapies.

Methods: Patients with DLBCL and ≥2 prior therapies received intravenous (IV) obinutuzumab pretreatment (1000 mg) on day (D) 1, 7 days before the first glofitamab dose. IV glofitamab was administered with step-up dosing on D8 (2.5 mg) and D15 (10 mg) of cycle (C) 1, and at the target dose (30 mg) on D1 of C2 through 12 (each 21-day cycles). The primary endpoint was Independent Review Committee-assessed complete response (CR) rate, using Lugano 2014 criteria.

Results: As of March 14, 2022, 154 patients (median age, 66 y [range, 21-90 y]; Ann Arbor stage III/IV: 75%) had received ≥1 dose of study treatment. Median prior therapies received was 3 (range, 2-7; prior chimeric antigen receptor [CAR] T-cell therapy: 33%). Most patients (86%) were refractory to their most recent regimen. After 12.6 months’ median follow-up (range, 0-22 mo), overall response and CR rates were 52% and 39%, respectively. CR rates in patients with/without prior CAR T-cell therapy were 35% and 42%, respectively. At 12 months, an estimated 64% of responders and 78% of complete responders remained in response. Projected 12-month overall survival rate was 50%. Cytokine release syndrome (CRS) occurred in 63% of patients, primarily associated with initial doses, and was mostly grade 1 (47%) or grade 2 (12%). No glofitamab-related grade 5 (fatal) adverse events (AEs) occurred. Glofitamab-related AEs leading to discontinuation were uncommon (n=5 [3%]).

Conclusions: Fixed-duration glofitamab induces durable CRs and has a manageable safety profile in patients with R/R DLBCL and ≥2 prior therapies, including those with prior exposure to CAR T-cell therapy.

Funding: This study was funded by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of all authors, was provided by Anya Horton, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.

© 2022 American Society of Clinical Oncology (ASCO), Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. This abstract was also accepted and previously presented at the European Hematology Association Annual Congress 2022.

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A7 Ibrutinib Dose Modifications for Management of Cardiac Adverse Events in Patients With B-Cell Malignancies: Pooled Analysis of 10 Clinical Trials

Jackie Broadway-Duren, PhD, DNP, APRN, FNP-BC1; Deborah M. Stephens, DO2; Mickey S. Register, FNP-BC, MSN, MPH3; Emily Hsu, PhD3; Sima Patel, PhD3; Melanie Tran, PharmD3; Michael Wang, MD1; Jan A. Burger, MD, PhD1; Maria Badillo, MSN, RN, OCN, CCRP1

1The University of Texas MD Anderson Cancer Center, Houston, TX; 2Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; 3AbbVie, North Chicago, IL

Background: Continuous therapy with once-daily ibrutinib is associated with long-term progression-free survival (PFS) in patients with B-cell malignancies. Dose adjustment is a potential approach for managing adverse events (AEs), which may optimize treatment outcomes. Due to their frequent and direct interactions with patients, nurses are essential in providing treatment-related support and information to patients regarding AE management, which may increase treatment adherence, thereby maximizing clinical benefit.

Objectives: To evaluate outcomes following dose reductions in ibrutinib-treated patients with cardiac AEs and to share nursing experience-based insights on AE management.

Methods: Data were pooled for ibrutinib-treated patients from 10 clinical studies of chronic lymphocytic leukemia (n=781), mantle cell lymphoma (MCL; n=250), marginal zone lymphoma (MZL; n=63), or Waldenström macroglobulinemia (n=169). Initial and recurrent cardiac AEs were identified by preferred terms within the cardiac disorders system organ class. Recurrence was defined as an AE of same or worse grade and was measured up to 30 days after the last dose of ibrutinib or at the start of next-line therapy, whichever occurred earlier.

Results: Overall, 234 of 1263 patients (19%) had cardiac AEs of any grade. Twelve patients were excluded from the analysis: 9 who had a dose reduction prior to a cardiac AE (0.7%) and 3 who had a fatal cardiac AE with no prior cardiac AE (0.2%). Of the remaining 222 patients with grade 1-4 cardiac AEs, 22 (10%) had ibrutinib dose reduction after a cardiac AE to: 420 mg (n=3), 280 mg (n=10), or 140 mg (n=9). These patients (n=22), compared with those without dose reduction (n=200), tended to be older (n=200) (≥75 years: 45% vs 29%, respectively), were less heavily pretreated (≥1 prior therapy: 45% vs 73%, respectively), and had a lower ibrutinib discontinuation rate (23% vs 48%, respectively). Recurrence of the same cardiac AE at the same or worse severity was less frequent in patients with dose reductions versus those without dose reduction, both overall (14% vs 19%, respectively) and as serious AEs (5% vs 11%, respectively). No patient died due to cardiac AE recurrence. Among patients with cardiac AEs who started with the 420-mg ibrutinib dose (177/222; excludes 45 patients with MCL or MZL who, per label, started with a 560-mg dose), no cardiac AE recurred at the same or worse severity in the subset with dose reductions, whereas cardiac AEs recurred in 19% of patients without dose reductions overall, with recurrence as a serious AE in 11%. PFS was not negatively impacted by dose reduction, both overall (n=22; median PFS not reached [NR]; 24-month PFS rate, 91%), and in those who started with the 420-mg dose (n=18; median PFS NR; 24-month PFS rate, 94%). Nursing insights on patient education and AE management will be presented.

Conclusions: Dose reduction for cardiac AEs may enable patients to continue to benefit from long-term ibrutinib and mitigates the risk of cardiac AE recurrence or worsening. Nurses can educate patients on identifying and monitoring AEs, explain how to report AEs, and support treatment persistence by reassuring patients that AEs can be successfully managed by continuation of ibrutinib with dose reduction without compromising efficacy.

Funding: This study was funded by Pharmacyclics LLC, an AbbVie Company.

This abstract was previously submitted to the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting. The content of the abstract has since been updated with new information.

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A8 Impact of Red Blood Cell Transfusions on Quality of Life for Patients With Myelofibrosis in the SIMPLIFY-1 and SIMPLIFY-2 Clinical Trials

Ruben Mesa, MD1; Francesca Palandri, MD2; Srdan Verstovsek, MD3; Lucia Masarova, MD3; Claire Harrison, DM4; Flora Mazerolle, MSc5; Manal M’hari, MSc5; Zhaohui Wang, MSc6; Catherine Ellis, PhD6; Samineh Deheshi, PhD6; Jun Kawashima, MD7; Robyn von Maltzahn, MSc8; Antoine Regnault, PhD5; Boris Gorsh, PharmD6

1Wake Forest University School of Medicine, Winston-Salem, NC; 2IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 3The University of Texas MD Anderson Cancer Center, Houston, TX; 4Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 5Modus Outcomes, Lyon, France; 6GSK plc, Philadelphia, PA; 7Sierra Oncology, a GSK company, San Mateo, CA; 8GSK plc, London, UK

Background: Patients with the rare blood cancer myelofibrosis often have symptoms (eg, tiredness, weakness, shortness of breath) that have a negative impact on their quality of life and daily activities.1-3 Some of these symptoms may be due to anemia, which is common in myelofibrosis and is often treated with RBC transfusions.4 However, the time, costs, and potential medical complications associated with transfusions can further decrease quality of life for these patients.4-6

Objective: To characterize the relationship between transfusions and patient quality of life in myelofibrosis, we performed an analysis of patient-reported outcomes based on transfusions received in the phase 3 SIMPLIFY-1 and SIMPLIFY-2 clinical trials.

Methods: The analysis included 432 patients treated with either the Janus kinase 1 and 2 (Jak1/Jak2)/activin A receptor type 1 inhibitor momelotinib or the Jak1/Jak2 inhibitor ruxolitinib in SIMPLIFY-1 (these patients had not been previously treated with a Jak inhibitor); as well as 156 patients treated with either momelotinib or the best available therapy (which was ruxolitinib in 88.5% of patients) in SIMPLIFY-2 (these patients had been previously treated with a Jak inhibitor) for 24 weeks.7,8 Patients were classified as transfusion independent (TI) if they had no transfusions and all blood hemoglobin levels were ≥8 g/dL in the previous 12 weeks; and transfusion dependent (TD) if they had ≥4 units transfused or a hemoglobin level <8 g/dL.

Results: The results of the SF-36v2® Health Survey, a quality-of-life survey,9 at baseline were available for 503 of the 588 patients in SIMPLIFY-1 and SIMPLIFY-2 clinical trials. Compared with the general population average score of 50, average baseline scores were lower in all quality-of-life areas assessed (average score range, 39.0-46.3) in the SIMPLIFY-1 and SIMPLIFY-2 patients. Furthermore, at both baseline and week 24, average scores were lower for TD patients than for those who were TI. Among the 150 patients who were TD at baseline, 75 were still TD, 40 became TI, 21 became TR, and 14 did not have results available at week 24. The group who became TI at week 24 had greater improvement (positive average score change vs baseline score) in most quality-of-life areas assessed, compared with those who remained TD.

Conclusions: In these myelofibrosis clinical trials, patient quality of life was worse on average compared with the general population. Patients who were TD had worse quality of life than those who were TI, highlighting the fact that transfusions further negatively impact quality of life for patients with myelofibrosis. Patients who were TD at baseline but became TI at week 24 had greater improvements in quality of life than those who remained TD, demonstrating the potential benefits of helping patients to need fewer transfusions by using other treatment options for anemia.

© 2023 American Society of Clinical Oncology (ASCO), Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.


  1. Langlais BT, Geyer H, Scherber R, Mesa RA, Dueck AC. Quality of life and symptom burden among myeloproliferative neoplasm patients: do symptoms impact quality of life? Leuk Lymphoma. 2019;60(2):402-408.
  2. Harrison CN, Koschmieder S, Foltz L, et al. The impact of myeloproliferative neoplasms (MPNs) on patient quality of life and productivity: results from the international MPN Landmark survey. Ann Hematol. 2017;96(10):1653-1665.
  3. Mesa R, Miller CB, Thyne M, et al. Myeloproliferative neoplasms (MPNs) have a significant impact on patients' overall health and productivity: the MPN Landmark survey. BMC Cancer. 2016;16:167.
  4. Naymagon L, Mascarenhas J. Myelofibrosis-related anemia: current and emerging therapeutic strategies. Hemasphere. 2017;1(1):e1.
  5. Tefferi A, Hudgens S, Mesa R, et al. Use of the functional assessment of cancer therapy–anemia in persons with myeloproliferative neoplasm-associated myelofibrosis and anemia. Clin Ther. 2014;36(4):560-566.
  6. Gerds AT, Harrison C, Thompson S, Snopek F, Pemmaraju N. The burden of illness and the incremental burden of transfusion dependence in myelofibrosis in the United States. Poster presented at: American Society of Hematology (ASH) Annual Meeting; December 10-13, 2022; New Orleans, LA. Poster 1729.
  7. Mesa RA, Kiladjian J-J, Catalano JV, et al. SIMPLIFY-1: a phase III randomized trial of momelotinib versus ruxolitinib in Janus Kinase inhibitor-naive patients with myelofibrosis. J Clin Oncol. 2017;35(34):3844-3850.
  8. Harrison CN, Vannucchi AM, Platzbecker U, et al. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol. 2018;5(2):e73-e81.
  9. Maruish ME, ed. User’s Manual for the SF-36v2 Health Survey. 3rd ed. QualityMetric Incorporated; 2011.
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A9 Long-term Safety of Avelumab First-line Maintenance for Advanced Urothelial Carcinoma in the JAVELIN Bladder 100 Trial

Joaquim Bellmunt, MD1; Jeanny B. Aragon-Ching, MD2; Miguel A. Climent Duran, MD3; Srikala S. Sridhar, MD4; Thomas Powles, MBBS, MRCP, MD5; Paul Cislo, PhD6; Elisabete Michelon, MD6; Alessandra di Pietro, MD, PhD7; Petros Grivas, MD, PhD8

1Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; 2Inova Schar Cancer Institute, Fairfax, VA; 3Instituto Valenciano de Oncología, Valencia, Spain; 4Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; 5Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew’s Hospital, London, UK; 6Pfizer, New York, NY; 7Pfizer srl, Milano, Italy; 8University of Washington; Fred Hutchinson Cancer Center, Seattle, WA

Background: In the JAVELIN Bladder 100 trial (NCT02603432), patients with advanced urothelial carcinoma (aUC) without progression after first-line (1L) platinum-based chemotherapy had significantly prolonged overall survival with avelumab 1L maintenance plus best supportive care (BSC) versus BSC alone. Safety was consistent with prior avelumab studies. Avelumab 1L maintenance is now standard-of-care treatment in international guidelines.

Objective: To evaluate the long-term safety of avelumab 1L maintenance treatment in patients with aUC, assessed via post hoc analyses performed with a minimum follow-up of 2 years in all patients.

Methods: In the phase 3 JAVELIN Bladder 100 trial, eligible patients had unresectable locally advanced or metastatic UC without progression after 1L platinum-based chemotherapy. In this study, we analyzed the long-term safety in patients who received 1L maintenance treatment in the avelumab plus BSC arm. Trial treatment continued until confirmed progression, unacceptable toxicity, or withdrawal of consent. At data cutoff (June 4, 2021), median follow-up in the avelumab arm was 38.0 months.

Results: In 344 patients who received ≥1 dose of avelumab, median treatment duration was 5.8 months (range, 0.5-49.7 mo). Treatment-related adverse events (TRAEs) of any grade occurred in 269 patients (78.2%) and were grade ≥3 in 67 (19.5%); 40 patients (11.6%) had a TRAE that led to avelumab discontinuation. Immune-related AEs (irAEs) of any grade occurred in 111 patients (32.3%) and were grade ≥3 in 26 (7.6%). The most common irAE categories of any grade (>5%) were thyroid disorders (n=44; 12.8%) and immune-related rash (n=37; 10.8%), and of grade ≥3 (>1%) were rash and hepatitis (each n=5; 1.5%). Serious irAEs occurred in 18 patients (5.2%); 21 patients (6.1%) had irAEs that led to avelumab discontinuation. Among 118 patients treated with avelumab for ≥12 months, irAEs occurred after 12 months in 27 (22.9%), including grade ≥3 irAEs in 5 patients (4.2%). No category of grade ≥3 irAEs occurred after 12 months in >1 patient.

Conclusions: Post hoc analyses from the JAVELIN Bladder 100 trial confirm the acceptable long-term safety profile of avelumab 1L maintenance therapy. Grade ≥3 TRAEs or irAEs occurred in relatively low proportions of patients, and no new safety signals were identified with longer treatment. These results further support the use of avelumab 1L maintenance until progression as standard of care for patients with aUC without progression after 1L platinum-based chemotherapy.

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A10 Mosunetuzumab Monotherapy Demonstrates Durable Efficacy and Manageable Safety in Patients With Relapsed/Refractory Follicular Lymphoma and ≥2 Prior Therapies: Updated Results From a Pivotal Phase 2 Study

Nancy L. Bartlett1; Laurie H. Sehn2; Matthew Matasar3; Stephen J. Schuster4; Sarit Assouline5; Pratyush Giri6; John Kuruvilla7; Miguel Canales8; Sascha Dietrich9; Keith Fay10; Matthew Ku11; Loretta Nastoupil12; Michael C. Wei13; Shen Yin13; Iris To13; Huang Huang14; Juliana Min15; Christopher R. Bolen13; Elicia Penuel13; L. Elizabeth Budde16

1Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO; 2BC Cancer Centre for Lymphoid Cancer and University of British Columbia, Vancouver, BC, Canada; 3Memorial Sloan Kettering Cancer Center, New York, NY; 4Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; 5Jewish General Hospital, McGill University, Montreal, QC, Canada; 6Royal Adelaide Hospital, Adelaide, Australia; 7Princess Margaret Cancer Centre, Toronto, ON, Canada; 8Hospital Universitario La Paz, Madrid, Spain; 9Universitat Heidelberg, Heidelberg, Germany; 10St Vincent's Hospital and Royal North Shore Hospital, Sydney, Australia; 11St Vincent's Hospital, University of Melbourne, Melbourne, Australia; 12MD Anderson Cancer Center, Houston, TX; 13Genentech, Inc, South San Francisco, CA; 14Hoffmann-La Roche Ltd, Mississauga, ON, Canada; 15Roche Products Ltd, Welwyn Garden City, UK; 16City of Hope, Duarte, CA

Background: Mosunetuzumab is a first-in-class CD20xCD3 T-cell engaging bispecific antibody that redirects T-cells to eliminate malignant B-cells. In a pivotal phase 2 study (NCT02500407), fixed-duration mosunetuzumab demonstrated a high rate of complete responses (CRs) and durable responses in patients with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior therapies.

Objective: To present updated data from this phase 2 study of mosunetuzumab in patients with R/R FL after 28.3 months’ median follow-up.

Methods: Patients with grade 1-3a FL and ≥2 prior therapies were enrolled. Intravenous mosunetuzumab was administered with step-up dosing in Cycle 1 (21-day cycles) for 8 cycles if CR by Cycle 8, and for 17 cycles if partial response or stable disease by Cycle 8. The primary endpoint was CR rate. Post hoc analyses compared investigator-assessed efficacy outcomes with mosunetuzumab versus last prior therapy, and the correlation between cytokine release syndrome (CRS) and tumor response.

Results: Ninety patients were enrolled. Median age was 60 years (range: 29-90 y), and 77% of patients had stage III/IV disease. Investigator-assessed objective response rate (ORR) and CR rate were 78% and 60% with mosunetuzumab, respectively, versus 56% and 36% with last prior therapy, respectively. Median progression-free survival (PFS) per investigator assessment was 24 months with mosunetuzumab versus 12 months with last prior therapy; 24-month PFS was 48% with mosunetuzumab. Mosunetuzumab improved median duration of response versus last prior therapy (not reached [NR] vs 12 mo, respectively), median duration of CR (NR vs 15 mo, respectively); and time-to-next therapy or death (NR vs 17 mo, respectively). CRS events, experienced by 44% of patients, were mainly (95%) grade 1/2; all CRS events resolved. Since the previous analysis, no new CRS events, or fatal, serious, or grade ≥3 adverse events were reported. ORRs were similar in patients with or without CRS events.

Conclusion: Durable responses continued to be observed with mosunetuzumab. The safety profile, with predominantly low-grade CRS events, supports outpatient administration of mosunetuzumab and was consistent with previous analyses. Comparable clinical response was observed regardless of CRS occurrence.

Funding: This study is sponsored by Genentech, Inc. Third-party medical writing assistance, under the direction of all authors, was provided by Emily Lynch, PhD, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.

These data have been previously presented at the American Society of Hematology Annual Meeting 2022 and the Hematology/Oncology Pharmacy Association Annual Conference 2023.

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A11 Patient-Reported Outcomes in Metastatic Nonsquamous Non–Small Cell Lung Cancer: PERLA Trial Comparing First-line Chemotherapy Plus Dostarlimab or Pembrolizumab

Martin Reck, MD, PhD1; Ana Laura Ortega Granados, MD2; Filippo de Marinis, MD3; Oren Meyers, PhD4; Susan Boklage, MS, MPH4; Qin Shen, PhD4; Lillian Cho, PharmD4

1Lungen Clinic, Airway Research Center North, Center for Lung Research, Grosshansdorf, Germany; 2Servicio de Oncología Médica, Hospital Universitario de Jaén, Spain; 3European Institute of Oncology, Milan, Italy; 4GSK, Collegeville, PA

Background: PERLA (NCT04581824) is a global, randomized, phase 2, double-blind study assessing the efficacy and safety of chemotherapy plus dostarlimab (dostCT) or chemotherapy plus pembrolizumab (pembCT) as first-line treatment for patients with metastatic nonsquamous non–small cell lung cancer (NSCLC). Previous results showed that dostCT had similar efficacy and safety to pembCT.1

Objective: To examine and report patient-reported outcomes (PROs) from patients with NSCLC who received either dostCT or pembCT in the PERLA trial.

Methods: Patients with Eastern Cooperative Oncology Group performance status 0/1 (fully active or active but restricted in physically strenuous activity) were randomized 1:1 to receive dostCT or pembCT every 3 weeks for up to 35 cycles. PROs were collected at baseline, every 3 weeks until cycle 4, every 9 weeks until cycle 16, every 12 weeks until end of treatment, and at the 30-day safety follow-up. PRO questionnaires, the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-LC13, were used to measure patients’ perspectives on symptoms and their impacts; QLQ-C30 is a health-related quality-of-life assessment for any cancer, and QLQ-LC13 is lung-cancer specific. Changes in patients’ scoring from baseline were described and were analyzed using a longitudinal mixed model. Least-squares means were calculated to quantify change observed over time. Changes of ≥10 points were considered clinically meaningful. Time to deterioration (TTD) in scores from QLQ‑C30 and selected QLQ‑LC13 symptoms were estimated using Kaplan-Meier statistical methods.

Results: Analysis populations for QLQ-C30 and QLQ-LC13 included 102 and 96 patients from the dostCT arm, respectively, and 99 and 90 patients from the pembCT arm, respectively. QLQ-C30 and QLQ-LC13 completion rates at cycle 13 (C13; ≈1 year of treatment) were 55.0% and 54.2%, respectively, for dostCT, and 37.1% and 35.7%, respectively, for pembCT. Scores for both questionnaires remained stable from baseline to C13, including function subscales (eg, physical, role) and symptom subscales (eg, pain, cough, dyspnea). No clinically meaningful differences between treatment arms in changes from baseline were observed. Across most subscales, >60% of patients in both arms showed stable or improved responses up to C13. At C13, more patients in the dostCT arm versus the pembCT arm reported meaningful improvements in chest pain (34.4% vs 10.0%, respectively) and dyspnea (40.6% vs 25.0%, respectively). TTDs were comparable between treatment arms, except for dyspnea (4.24 mo, dostCT vs 1.54 mo, pembCT).

Conclusions: Health-related quality of life, as measured by PRO questionnaires, was similar and stable through C13 in both treatment arms. Results supplement the efficacy and safety data from PERLA1 and support further investigation of dostarlimab as an appropriate programmed cell death 1 inhibitor for use in combination with standard of care and novel therapies in metastatic NSCLC.

Funding: This study was sponsored by GSK. Editorial support was provided by ArticulateScience, LLC, funded by GSK.

© 2023 American Society of Clinical Oncology (ASCO), Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.


  1. Peters S, et al. Immunooncol Technol. 2022;16(suppl 1). Abstract 57O.
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A12 Patient-reported Outcomes in Patients With Primary Advanced or Recurrent Endometrial Cancer Who Received Dostarlimab Plus Carboplatin-Paclitaxel vs Carboplatin-Paclitaxel in the ENGOT-EN6/GOG3031/RUBY Trial

Mansoor Raza Mirza, MD1; Matthew A. Powell, MD2; Caroline Lundgren3; Vladyslav Sukhin4; Bhavana Pothuri, MD5; Lucy Gilbert, MD6; Sarah E. Gill, MD7; Graziana Ronzino8; Nicole Nevadunsky, MD9; Stefan Kommoss10; Lyndsay Willmott, MD11; Ingrid Boere, MD12; Cara Mathews, MD13; Joseph Buscema, MD14; Michael G. Teneriello, MD, FACOG15; Mark S. Shahin, MD16; Oren Meyers, PhD17; Jamie Garside, MSc18; Robert L. Coleman, MD19; Brian Slomovitz, MD20

1Rigshospitalet, Copenhagen University Hospital, Denmark; Nordic Society of Gynaecologic Oncology–Clinical Trial Unit, Copenhagen, Denmark; 2Washington University, St Louis, MO; 3Karolinska University Hospital, Stockholm, Sweden; 4Grigoriev Institute for Medical Radiology and Oncology, National Academy of Medical Science of Ukraine, Kharkov, Ukraine; 5Gynecologic Oncology Group and Perlmutter Cancer Center, NYU Langone Health, New York, NY; 6McGill University Health Centre, Montreal, QC, Canada; 7Nancy N. and J.C. Lewis Cancer and Research Pavilion, Savannah, GA; 8Ospedale “Vito Fazzi”, Lecce, Italy; 9Albert Einstein College of Medicine, New York, NY; 10Tübingen University Hospital, Tübingen, Germany; 11Arizona Center for Cancer Care, Phoenix, AZ; 12Erasmus MC, Rotterdam, the Netherlands; 13Legorreta Cancer Center, Warren Alpert Medical School of Brown University, Providence, RI; 14Arizona Oncology Associates, Tucson, AZ; 15US Oncology Research, The Woodlands, TX; 16Sidney Kimmel Medical College of Thomas Jefferson University, Jefferson Abington Hospital, Abington, PA; 17GSK, Collegeville, PA; 18GSK, London, UK; 19Texas Oncology, Sarah Cannon Research Institute, Nashville, TN; 20Mount Sinai Medical Center, Miami Beach, FL

Background: RUBY (NCT03981796) is a phase 3, randomized, placebo-controlled trial in patients with primary advanced or recurrent endometrial cancer (pA/rEC). In RUBY, dostarlimab plus carboplatin-paclitaxel (D+CP) demonstrated clinically meaningful efficacy in patients with pA/rEC, including a significant improvement in progression-free survival (PFS), compared with placebo (PBO) plus carboplatin-paclitaxel (PBO+CP).1

Objective: To examine and report similarities and differences in patient-reported outcomes (PROs) in patients with pA/rEC who received either D+CP or PBO+CP in the phase 3 RUBY trial.

Methods: A total of 494 patients with pA/rEC were randomized 1:1 to receive either D+CP or PBO+CP every 3 weeks for 6 cycles, followed by D or PBO alone every 6 weeks for up to 3 years or until disease progression. As a secondary endpoint, PRO questionnaires for patients with any cancer (ie, the European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30) and for patients with endometrial cancer (ie, EORTC QLQ-EN24) were administered on day 1 of each treatment cycle (C), at end of treatment, and at safety and survival follow-up points. Changes in patients’ scores over time were calculated using mixed model for repeated measures analyses, and least-squares means (LSMs) were used to quantify the difference between treatment arms in change observed in patients’ scores over time. Results are reported here for C7 (the end of chemotherapy) and C13 (the end of 1 year of study follow-up).

Results: PRO scores were similar in patients who received D+CP and PBO+CP through the chemotherapy period (C7). After 1 year of study follow-up (C13), the mean change in global health status/quality-of-life (GHS/QoL) score from baseline was 3.3 (SD, 23.51) with D+CP, and −0.9 (SD, 19.25) with PBO+CP (positive score indicates improvement; ≥10-point change was considered clinically meaningful). Over the 3-year study period, no differences between the 2 treatment arms were detected (P≥.05 indicated no significant difference) based on LSMs; more specifically, GHS/QoL was 0.5 (P=.72), physical function was −0.7 (P=.63), fatigue was 0.2 (P=.91), and pain was −1.0 (P=.62). At the end of study treatment, patients who received D+CP reported improvement in back/pelvic pain compared with baseline; patients receiving PBO+CP reported worsening of GHS/QoL, social functioning, body image, and change in taste compared with baseline.

Conclusions: In this study, patients with pA/rEC receiving D+CP experienced significantly improved PFS while maintaining health-related QoL. These findings further support the use of D+CP as a standard of care in treating patients with pA/rEC.

Funding: This study was sponsored by GSK. Editorial support provided by ArticulateScience, LLC, and funded by GSK.

© 2023 American Society of Clinical Oncology (ASCO), Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.


  1. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388(23):2145-2158.
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A13 Patritumab Deruxtecan (HER3-DXd) in EGFR-Mutated NSCLC Following EGFR TKI and Platinum-Based Chemotherapy: HERTHENA-Lung01

Helena A. Yu, MD1; Yasushi Goto, MD2; Hidetoshi Hayashi, MD, PhD3; Enriqueta Felip, MD, PhD4; James Chih-Hsin Yang, MD, PhD5; Martin Reck, MD, PhD6; Kiyotaka Yoh, MD7; Se-Hoon Lee, MD, PhD8; Luis Paz-Ares, MD, PhD9; Benjamin Besse, MD, PhD10; Paolo Bironzo, MD, PhD11; Dong-Wan Kim, MD, PhD12; Melissa L. Johnson, MD13; Yi-Long Wu, MD14; Qian Dong, PhD15; Pang-Dian Fan, MD, PhD15; Pomy Shrestha, MBBS15; David W. Sternberg, MD, PhD15; Dalila Sellami, MD15; Pasi A. Jänne, MD, PhD16

1Memorial Sloan Kettering Cancer Center, New York, NY; 2National Cancer Center Hospital, Tokyo, Japan; 3Kindai University, Osaka, Japan; 4Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, Spain; 5National Taiwan University Hospital, Taipei City, Taiwan; 6German Center for Lung Research, LungenClinic, Grosshansdorf, Germany; 7National Cancer Center Hospital East, Kashiwa, Japan; 8Samsung Medical Center, Sungkyunkwan University School of Medicine, and Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Republic of Korea; 9Hospital Universitario, Spanish National Cancer Research Center, Universidad Complutense and Ciberonc, Madrid, Spain; 10Université Paris Saclay, Gustave Roussy, Villejuif, France; 11University of Torino, Torino, Italy; 12Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea; 13Tennessee Oncology, Sarah Cannon Research Institute, Nashville, TN; 14Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, China; 15Daiichi Sankyo, Inc, Basking Ridge, NJ; 16Dana-Farber Cancer Institute, Boston, MA

Background: For patients with epidermal growth factor receptor (EGFR)-mutated non–small cell lung cancer (NSCLC) posttreatment with EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC), safe and effective new therapies are needed. In a phase 1 study (NCT03260491), patritumab deruxtecan, U3-1402 (HER3-DXd), showed promising efficacy and a manageable safety profile in patients with advanced EGFR-mutated NSCLC following an EGFR TKI and PBC.

Objective: HER3-DXd is an antibody-drug conjugate consisting of a fully human monoclonal antibody to HER3 attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. Here, we report data from the phase 2 HERTHENA-Lung01 trial (NCT04619004).

Methods: This open-label study included patients with advanced EGFR-mutated NSCLC previously treated with an EGFR TKI and PBC. Patients were randomized to receive 1 of 2 dose schedules of HER3-DXd: 5.6 mg/kg IV Q3W or an up-titration regimen (3.2 mg/kg➞4.8 mg/kg➞6.4 mg/kg). Enrollment in the up-titration arm closed early based on a benefit-risk assessment of emerging phase 1 data; enrollment in the 5.6-mg/kg arm was completed. The primary endpoint was confirmed ORR by blinded independent central review (BICR) per RECIST version 1.1. Intracranial responses were measured by BICR per CNS RECIST.

Results: Two hundred twenty-five patients received HER3-DXd 5.6 mg/kg. As of May 18, 2023, median study duration was 18.9 months (range, 14.9-27.5 mo). Confirmed ORR by BICR was 29.8% (95% CI, 23.9%-36.2%); median DOR, 6.4 months (95% CI, 4.9-73.8); PFS, 5.5 months (95% CI, 5.1-5.9); and OS, 11.9 months (95% CI, 11.2-13.1). Patients with prior osimertinib had similar outcomes. Activity was observed across a broad range of HER3 expression and diverse mechanisms of EGFR TKI resistance. In patients with nonirradiated brain metastases (n=30), confirmed CNS ORR was 33.3% (95% CI, 17.3%-52.8%; 9/30 CR, 1/30 PR); DCR was 76.7%. At the primary data cutoff (November 21, 2022), median treatment duration was 5.5 months (range, 0.7-18.2 mo). Adverse events (AEs) were manageable and tolerable: Drug-related AEs were associated with discontinuation in 10 patients (4.4%) and death in 4 (1.8%); 45.3% had grade (G) ≥3 drug-related AEs; 12 patients (5.3%) had independently adjudicated drug-related interstitial lung disease (G1/2, n=9; G3, n=2; G5, n=1).

Conclusions: In this patient population with significant unmet need and limited therapeutic options, HER3-DXd demonstrated clinically meaningful efficacy; moreover, this study provides the first report of HER3-DXd efficacy in the CNS. The safety profile was manageable and consistent with previous observations. Overall, HER3-DXd is a promising therapy for patients with previously treated EGFR-mutated NSCLC. A phase 3 trial in EGFR-mutated NSCLC after progression on EGFR TKI is ongoing (HERTHENA-Lung02; NCT05338970).

Funding: This study was funded by Daiichi Sankyo.

This abstract was previously submitted to the 2023 World Conference on Lung Cancer.

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A14 Symptoms and Impacts Important to Patients With Advanced/Metastatic Non–Small Cell Lung Cancer: Results of a Qualitative Research Study

Anna Cardellino, MPH1; Manasee Shah, MPH1; Jennifer Hanlon, MPH2*; Sara Taiyari, MSc3; Kimberly Kelly, PhD4; Aude Roborel de Climens, PhD5; Alexander Stojadinovic, MD1

1GSK, Collegeville, PA; 2GSK, Waltham, MA; 3GSK, Stevenage, UK; 4IQVIA, New York, NY; 5IQVIA, Paris, France
*Affiliation at time of study.

Background: Non–small cell lung cancer (NSCLC) causes significant symptom burden, particularly at advanced stages.

Objectives: To gain insight into patients’ experience of advanced/metastatic (adv/met) NSCLC and to identify the symptoms and daily life impacts of importance to patients.

Methods: Semistructured, qualitative interviews using open-ended questions and lasting 45 to 60 minutes were conducted by telephone/virtual platform with US patients with a confirmed diagnosis of adv/met NSCLC to explore symptomatology and disease impacts on daily life.

Results: Overall, 19 patients (aged 28-71 y; 95% female) were interviewed. Most patients were receiving targeted therapy (63%) and were diagnosed with adv/met NSCLC more than 12 months prior (79%). Patients frequently reported 14 symptoms, with the most common being shortness of breath/difficulty breathing (n=16), fatigue (n=16), cough (n=13), and pain (eg, chest, back; n=9). Patients had difficulty distinguishing disease-related symptoms from treatment-related symptoms, particularly cough, fatigue, and shortness of breath/difficulty breathing. Gastrointestinal symptoms (n=9), hair/skin/nail issues (n=4), sensory changes (eg, vision/taste; n=3), and swelling (n=2) were described as treatment-related symptoms. Patients reported impacts on physical functioning (mainly difficulty walking [n=16]), psychological well-being (mainly anxiety/depression [n=16]), and activities of daily living (ADLs; mainly difficulty performing daily tasks [n=13]). Walking and ADLs were impacted by fatigue and shortness of breath, although pain also contributed to difficulty with ADLs. Patients linked coughing to impaired ability to sleep, impacts on ADLs like conversations/laughing, and impacts on psychological well-being.

Conclusions: These interviews indicate that patients with adv/met NSCLC are negatively impacted by disease-related and treatment-related symptoms. Understanding the symptoms and impacts most relevant to patients can help inform which patient-reported outcomes reflect treatment benefits in clinical trials and can support treatment decision-making in clinical practice.

Funding: GSK provided funding for this research study.

This abstract was previously submitted to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 25th Annual European Conference 2023.

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A15 VOCAL (Views of Ovarian Cancer Patients and Their Caregivers—How Maintenance Therapy Affects Their Lives) Study: Cancer-related Burden and Quality of Life of Caregivers

Soham Shukla, MS, PharmD1; Joanna de Courcy, BSc2; Hilary Ellis, BA2; Gary Milligan, BSc2; Teresa Taylor-Whiteley, PhD2; Amanda Golembesky, MS, PhD3; Dana Chase, MD4; Stephanie L. Wethington, MSc, MD5

1Value Evidence and Outcomes, GSK, Collegeville, PA; 2Adelphi Real World, Macclesfield, UK; 3GSK, Research Triangle Park, NC; 4Creighton University School of Medicine, Phoenix, AZ; 5The Kelly Gynecologic Oncology Service, Johns Hopkins Medicine, Baltimore, MD

Background: Caregivers for patients with ovarian cancer (OC) often carry a considerable emotional and financial burden.

Objective: This analysis evaluated sociodemographic characteristics and cancer-related burden in caregivers of patients with OC.

Methods: Adult caregivers of US patients with OC identified through patient advocacy groups, physicians, and panel groups completed online/paper surveys (English/Spanish). Outcomes included caregiver responsibilities, human impact (Zarit Burden Interview questionnaire), health-related quality of life (CarerQol-7D and EQ-5D-3L questionnaires), work impact, and financial impact.

Results: Caregivers (n=80) were diverse in age (mean, 47.3 y; range, 19-75 y), patient treatment (surveillance, 42%; IV treatment, 25%; daily pills, 23%; chemotherapy, 10%), and ethnicity (most common: White, 55%; Black, 20%; Hispanic/Latino, 10%). They were mainly partners/adult children of patients (85%). Most caregivers reported working/studying (64%) alongside caring. Despite providing support for a mean of 26.9 months, caregivers rarely received financial support (10%), and most household medical expenses were spent on the patient (mean monthly household medical costs, $263.00; mean monthly patient medical costs, $213.40). To provide care, 25% of caregivers changed living arrangements. Emotional (92%) and logistical supports (travel, 74%; shopping, 69%; preparing meals, 62%) were most frequent, often at high/substantial levels (emotional, 71%; travel, 55%; shopping, 53%; preparing meals, 40%). Most nonresident caregivers (19%) travelled by car (73%) and often over 5 miles (53%) to provide support. Caregivers reported moderate/extreme anxiety/depression (55%) and moderate/severe burden of care (33%). Mean CarerQol-7D utility score for informal care situation was 73.8 (range, 0-100; best-worst informal care situation), and 52% were physically healthy.

Conclusions: Caregivers of patients with OC reported burdens including anxiety/depression, work/financial impact, and quality-of-life impairment. Further investigations are needed to determine effects of specific patient treatments on caregivers and interventions to assist in providing care. Additionally, future research could assess caregiver burden by patient and disease characteristics.

Funding: This study (214511) was sponsored by GSK, Waltham, MA. Editorial support for the original abstract was provided by Fishawack Health and funded by GSK. The editorial and reformatting support for this encore abstract was funded by GSK (Waltham, MA) and provided by Ashfield MedComms, an Inizio company. Data presented on behalf of the original authors with their permission.

This abstract was previously presented at the Professional Society for Health Economics and Outcomes Research/International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Europe 2022 Meeting; November 6-9, 2022; Vienna, Austria. Reused with permission.

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