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August 2016 VOL 7, NO 7
ASCO 2016 Annual Meeting
More than 30,000 healthcare professionals from around the world attended the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting in Chicago, IL. The theme of this year’s meeting was Collective Wisdom: The Future of Patient-Centered Care and Research. More than 5200 abstracts were submitted, each of which had a goal of ultimately advancing the delivery and accessibility of high-quality cancer care. We have selected a few of these presentations and hope you find them of interest.
Novel Antibody in Gastric Cancer
The first-in-class antibody IMAB362 extended survival in advanced gastric cancer when added to standard chemotherapy with epirubicin, oxaliplatin, and capecitabine (EOX), according to results from the international, multicenter, randomized phase 2 FAST study.
Median overall survival (OS) was significantly longer in patients treated with IMAB362 than in those treated with standard chemotherapy and was more robust in patients with the highest levels of claudin18.2 (CLDN18.2) expression.
IMAB362 is a chimeric monoclonal antibody that mediates specific killing of CLDN18.2-positive cancer cells via immune effector mechanisms. CLDN18.2 is a tight junction protein commonly expressed in 70% to 90% of biliary duct, pancreatic, gastric, and mucinous ovarian cancers.
The study included 161 patients with advanced or recurrent gastric, esophageal, or gastroesophageal junction adenocarcinoma with CLDN18.2 expression of at least 2+ intensity in at least 40% of cancer cells and an ECOG performance status of 0 or 1. None of the patients was eligible for trastuzumab.
All 161 patients received first-line treatment with standard chemotherapy using the triplet EOX combination (epirubicin and oxaliplatin on day 1 of each cycle and capecitabine twice daily on days 1 through 21 of each cycle) for a maximum of 8 cycles. In addition, 77 patients were treated with a loading dose of IMAB362 800 mg/m2 followed by IMAB362 600 mg/m2; the remaining 84 patients served as the control group.
An additional group of 85 patients were treated with the same first-line chemotherapy regimen plus a higher dose of IMAB362, but these results were not reported at ASCO.
Patients treated with the antibody plus chemotherapy had significantly improved progression-free survival (PFS) compared with patients treated with chemotherapy alone: 7.9 months versus 4.8 months, respectively (P = .0001). OS was also significantly superior in patients treated with the antibody plus chemotherapy: 13.2 months versus 8.4 months, respectively (P = .0001).
Patients with the highest level of CLDN18.2 expression (at least 2+ intensity in at least 70% of tumor cells) achieved more robust efficacy with the antibody added to chemotherapy. In this subgroup, median PFS was 7.2 months versus 5.6 months in controls (P ≤.0005). Median OS was 16.7 months versus 9 months, respectively (P ≤.0005).
Adverse events were manageable. The most common antibody-related adverse events were vomiting, neutropenia, and anemia. The rate of grade 3/4 neutropenia was higher in the antibody group (32.5%) compared with controls (21.4%). The rate of grade 3/4 vomiting was 10.4% versus 3.6%, respectively.
Commenting on this trial, Peter Enzinger, MD, of Dana-Farber Cancer Institute in Boston, MA, said that results were promising, but before moving on to phase 3 trials of the antibody, it would be good to confirm that the expression of CLDN18.2 is a biomarker and also to determine which drugs are best partnered with the antibody, based on toxicity profiles.
Al-Batran S-E, Schuler MH, Zvirbule Z, et al. FAST: an international, multicenter, randomized, phase II trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without IMAB362, a first-in-class anti- CLDN18.2 antibody, as first-line therapy in patients with advanced CLDN18.2+ gastric and gastroesophageal junction (GEJ) adenocarcinoma. J Clin Oncol. 2016;34(suppl). Abstract LBA4001.
Nivolumab in Anal Cancer
Immunotherapy has gained a foothold in the treatment of melanoma and lung cancer, and it is also being studied in other solid tumors. A small, prospective phase 2 trial suggests that the programmed death-1 (PD-1) inhibitor nivolumab can improve outcomes in metastatic anal cancer.
In a study of 37 patients with refractory metastatic squamous cell carcinoma of the anal canal (SCCA), nivolumab achieved a 24% response rate, including 2 complete responses.
“Anal cancer refractory to chemotherapy and radiation can respond to PD-1 inhibitory agents. [This is] good news to bring home to our clinics,” said Richard Goldberg, MD, The Ohio State University Comprehensive Cancer Center–James Cancer Hospital and Solove Research Institute, Columbus. Dr Goldberg included this presentation in a “Highlights of the Day” session. He was not involved in this study.
This is the first prospective phase 2 study completed in patients with refractory SCCA in the United States. Single-agent nivolumab was well tolerated and met the primary end point of response.
“This opens the door to the use of immunotherapy in another one of the virally associated cancers, this one with human papillomavirus,” Dr Goldberg said.
“There is currently no standard of care for patients with metastatic refractory disease, which comprises about 20% of all patients with SCCA,” said lead author Cathy Eng, MD, of The University of Texas MD Anderson Cancer Center in Houston.
The study, part of the National Cancer Institute’s Experimental Therapeutics Clinical Trials Network, enrolled 37 patients treated with single-agent nivolumab. Median number of therapies was 2, and PD-1 ligand 1 (PD-L1) expression was not required for participation in the study.
Of 34 patients evaluable for response, 2 (5.4%) achieved a complete response and 7 (18.9%) a partial response, for an overall response rate of 24.3%. Seventeen patients (45.9%) had stable disease, and 8 (21.6%) had progressive disease. Median progression-free survival was 3.9 months.
Baseline levels of PD-L1 expression, PD-1 expression, and CD8 were increased in responders compared with nonresponders. There were few grade 3 toxicities, including fatigue, anemia, rash, and hyperthyroidism, and 1 case of pneumonitis.
Morris VK, Ciombor KK, Salem ME, et al. NCI9673: a multi-institutional eETCTN phase II study of nivolumab in refractory metastatic squamous cell carcinoma of the anal canal (SCCA). J Clin Oncol. 2016;34(suppl). Abstract 3503.
Brentuximab Vedotin as Alternative to Radiation
Brentuximab vedotin appears to be a promising alternative to radiation for consolidation therapy in patients with limited-stage Hodgkin lymphoma (HL) after induction chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).
The current standard of care for these patients is either 2 to 4 cycles of ABVD followed by consolidation radiation or 3 to 6 cycles of ABVD without radiation. Radiation appears to improve progression-free survival (PFS) but not overall survival (OS), so its use in patients with limited-stage HL remains controversial, explained Steven I. Park, MD, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill.
The phase 2 study presented by Dr Park found that more than 90% of patients with limited-stage nonbulky HL treated with ABVD and consolidation brentuximab vedotin were PET-negative. Moreover, those patients who were PET-negative after brentuximab vedotin consolidation remained in remission, with an estimated 1-year PFS of 100%.
“Radiation therapy, although effective, leads to long-term complications, including increased risk of secondary malignancies,” he said. “Patients who receive radiation to the mediastinum are at increased risk for breast cancer, lung cancer, and thyroid malignancies, and there is an increased risk of cardiac complications.”
When treating patients with limited-stage HL, secondary complications are an important consideration because these patients have a fairly long life expectancy, he explained. In the study, the median age was 29 years.
The phase 2 multicenter study enrolled 41 patients with newly diagnosed, limited-stage, nonbulky HL. They received 2 cycles of ABVD followed by an interim PET scan. Those with favorable disease characteristics who were PET-negative went on to consolidation therapy with brentuximab vedotin every 3 weeks for 6 cycles. The remaining patients were treated with an additional 2 to 4 cycles of ABVD based on risk factors and interim PET scan and were then treated with brentuximab vedotin consolidation. Those who were PET-negative after consolidation did not receive additional therapy, whereas PET-positive patients were treated with radiation.
After 2 cycles of ABVD, 72.5% of patients were PET-negative; after completion of brentuximab vedotin consolidation therapy, 94.4% were PET-negative.
At a median follow-up of 17 months, estimated 1-year PFS was 91% and estimated 1-year OS was 97%. Those patients who were PET-negative after 2 cycles of ABVD had an estimated 1-year PFS of 96% compared with 79% in those who were PET-positive at the interim scan.
After consolidation therapy, 2 patients relapsed. The most common adverse event was peripheral neuropathy. Other common adverse events included rash, fatigue, nausea, and neutropenia.
Park SI, Olajide OA, Reddy NM, et al. A phase 2 trial of ABVD followed by brentuximab vedotin consolidation in limited stage non-bulky Hodgkin lymphoma. J Clin Oncol. 2016;34(suppl). Abstract 7508.
Adjuvant temozolomide (TMZ) given after radiation improved survival in patients with anaplastic glioma without 1p/19q codeletion, a rare disease, according to early results from the phase 3 CATNON intergroup trial.
Estimated 5-year survival rates were 56% when patients received radiotherapy plus TMZ versus 44% without adjuvant TMZ. Use of TMZ delayed disease progression by more than 2 years in this trial of a very rare form of brain cancer.
Previous studies suggested that TMZ during and after radiation improved outcomes in glioblastoma, but chemotherapy after radiotherapy had no impact on anaplastic glioma, and outcomes were worse in patients with no 1p/19q codeletion. CATNON was designed to determine the role of TMZ in this worse-prognosis group of patients.
“Until this study, doctors had no evidence to support the use of adjuvant TMZ in patients with grade 3 anaplastic glioma. These findings should expand treatment choices and change the way we treat patients with this rare form of brain cancer,” said Martin J. Van Den Bent, MD, Erasmus MC Cancer Center, Rotterdam, the Netherlands.
Patients with no 1p/19q codeletion tend to respond better to chemotherapy and live longer, he explained. CATNON randomized 745 patients to 1 of 4 groups: radiation alone, radiation with concurrent TMZ, radiation with adjuvant TMZ, and radiation with both concurrent and adjuvant TMZ.
Median time to disease progression was more than double in patients treated with adjuvant TMZ: 42.8 months versus 19 months, respectively.
Median overall survival has not yet been reached in those who received adjuvant TMZ. Results of TMZ given only during radiation are not yet available and are expected in 2020.
The most common toxicities in the TMZ study arms were hematologic, with grade 3 and 4 toxicity reported in 8% to 13% of patients, respectively.
The next step is to identify biomarkers for response to TMZ. Candidate biomarkers include MGMT promotor methylation and IDH mutational status.
Van Den Bent MJ, Erridge S, Vogelbaum MA, et al. Results of the interim analysis of the EORTC randomized phase III CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q co-deletion: an intergroup trial. J Clin Oncol. 2016;34(suppl). Abstract LBA2000.
App Improved Survival
Patients with stage III and IV lung cancer who used a web-mediated app called Moovcare to track their symptoms had prolonged survival compared with those assigned to standard follow-up care in a randomized phase 3 trial.
At 1 year, 75% of the patients randomized to use the app were alive versus 49% of those in the standard care follow-up arm.
In addition, use of the app reduced resource utilization, including CT scans, visits to the doctor, and patient phone calls to the doctor’s office.
“If a drug could save this many lives it would make national headlines,” said Fabrice Denis, MD, PhD, a researcher at the Institut Inter-regional de Cancérologie Jean Bernard in Le Mans, France.
“Through personalized follow-up using this convenient and simple online application, we can detect complications and signs of relapse and offer appropriate care earlier. This approach introduces a new era of follow-up in which patients can give and receive continuous feedback between visits to their oncologist,” he told listeners.
Moovcare is a prototype in development and not yet commercially available. The app allows patients to self-report the status of 12 clinical symptoms of disease progression weekly. Caregivers were also allowed to enter information on behalf of the patient about emerging symptoms. The app analyzed the feedback on the 12 symptoms and reported results to the oncologist. An algorithm assessed changes in symptoms, which triggered e-mail alerts for the doctor, who would confirm the need for visits and changes in therapy.
The multicenter randomized study included 121 patients with stage III/IV lung cancer who completed initial chemotherapy, radiation therapy, or surgery. Patients were randomized to web-mediated follow-up with the app (n = 60) or standard care follow-up (n = 61), with doctor visits and CT scans every 3 to 6 months or more often if the investigator chose.
Relapse rates were similar in the groups: 51% for standard care follow-up and 49% for the app. Because the symptoms were reported earlier in the app group, these patients had better performance status, and 74% were able to tolerate the full recommended treatment at relapse versus one-third of patients randomized to standard follow-up, which explains the improved survival rates.
Overall quality of life, as assessed by the FACT-L, FACT-G, and FACT-L TOI, was better in the group that used the app. Use of the app also reduced the number of imaging tests per patient per year by 50%.
Other studies have looked at telemedicine in cancer patients, but, according to the researchers, this is the first to show improved survival with an app versus standard care follow-up. It is also the first study to use an algorithm for early detection of symptomatic relapse or complication, triggering early treatment or supportive care.
The app also reduced the frequency of patient and caregiver phone calls to the doctor. The app did not increase the time burden on the oncologist: it took the oncologist about 15 minutes per week to follow 60 patients using the app.
Use of the app is now being studied in patients with lymphoma, where CT scans are also used to follow patients, Dr Denis said.
Denis F, Lethrosne C, Pourel N, et al. Overall survival in patients with lung cancer using a web-application-guided follow-up compared to standard modalities: results of phase III randomized trial. J Clin Oncol. 2016;34(suppl). Abstract LBA9006.
Perception of Risk and QOL
Women with early breast cancer and a favorable prognosis commonly overestimate their risk of recurrence, which compromises their quality of life (QOL), according to a presentation of preliminary data that are part of a larger study.
The actual risk of recurrence among women with early breast cancer is <5% for ductal carcinoma in situ (DCIS) and <10% for invasive breast cancer. The large study found that 38% of patients with DCIS and 27% of patients with low-risk invasive (LRI) breast cancer substantially overestimated their risk of recurrence.
“We looked at the degree to which women with favorable prognosis overestimate their risk of recurrence and found it was substantial. This is important because these women are worried, and this could lead to increased utilization of services such as imaging, more tests, and more doctor visits. Patients with a favorable prognosis, such as DCIS or LRI, should be able to go on with their lives,” said lead author Sarah T. Hawley, PhD, of the University of Michigan Health System, Ann Arbor.
“Clinicians should be aware of the association between overestimation of risk, quality of life, and worry, and make more effort to communicate with these women and reassure them that they are at low risk. It is important to give patients a sense of their actual posttreatment risk of recurrence,” she stated.
The survey included 3880 women with newly diagnosed early-stage breast cancer from the SEER registries of Georgia and Los Angeles County who had surgical treatment in 2013 and 2014. Surveys were sent about 2 months following treatment, with a response rate of 71%. The final sample on which the study was based totaled 1025 women with DCIS or LRI (stage I, ER+/HER2−, grade 1/2).
Mean age was 61 years. Numeric overestimation was significantly associated with nonwhite race, more education, family history, invasive stage, and symptom bother (P <.05 for all). Descriptive overestimation was significantly associated with family history and symptom bother (P <.05 for both).
When respondents were asked about the frequency of worry about recurrence, those with LRI were about 50% more likely to worry than those with DCIS. Both numeric and descriptive overestimation measures of risk were associated with worse QOL on the PROMIS scale. However, descriptive overestimation was more strongly associated with poor outcomes than was numeric overestimation, suggesting that clinicians should be discussing actual risk in ways that patients can clearly understand.
Hawley ST, Janz NK, Griffith KA, et al. Recurrence risk perception and quality of life after treatment of breast cancer. J Clin Oncol. 2016;34(suppl). Abstract 6516.