A Critical Need for Novel Therapies in Metastatic Urothelial Cancer: TROPHY-U-01 Study

2021 Year in Review - Triple-Negative Breast Cancer


Urothelial Cancer

Checkpoint inhibitors (CPIs), specifically programmed death receptor 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors, are second-line treatments used for patients with platinum-resistant metastatic urothelial carcinoma (mUC), but response rates are also poor.1 This has created an unmet need for new treatment options for this disease. Sacituzumab govitecan-hziy (SG) was recently granted accelerated approval as a third-line treatment for patients with locally advanced or mUC who have progressed on platinum-based chemotherapy and a CPI.1

The TROPHY-U-01 phase 2 study evaluated SG in 113 patients with locally advanced or mUC after progression on platinum-based chemotherapy and CPI treatment, and demonstrated SG’s clinical activity in these patients.1 SG showed an overall response rate of 27% and was generally well-tolerated with a predictable and manageable safety profile.1 Results show that SG is a promising new antibody–drug conjugate with the potential to fulfil an unmet treatment need in patients with locally advanced or mUC after platinum-based chemotherapy and CPI therapy.1

The US Food and Drug Administration (FDA) granted SG accelerated approval for treating patients with locally advanced or mUC progressing after platinum and CPI therapy.2 Patients with mUC who develop resistance to platinum-based combination treatment and CPI therapy have few choices.3 In TROPHY-U-01, SG showed benefit to patients, with 77% of patients showing a reduction in quantifiable illness.3,4 In patients with pretreated mUC who have advanced on both platinum and CPI regimens, SG demonstrated an overall response rate of 27% versus historical therapies such as taxanes and vinflunine that have response rates of approximately 10%.3 Taxanes and vinflunine (approved in the European Union) are recommended by the National Comprehensive Cancer Network and the European Society for Medical Oncology. The median overall survival for these historical medicines is 7 to 8 months.3 More recent therapies include the accelerated FDA approvals of erdafitinib and enfortumab vedotin, both following platinum-based chemotherapy and CPI.3 Although both enfortumab vedotin and erdafitinib have objective response rates of approximately 40%, most patients progress on these treatments.3 Furthermore, erdafitinib is only available to patients who have an FGFR2/3 mutation or fusion, highlighting the unmet need for new therapies.3 The findings of this study, therefore, suggest that SG may be an option for this population.

The most common adverse reactions associated with SG treatment are neutropenia, nausea, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, decreased appetite, rash, and abdominal pain, all with an incidence of ≥25%.5 SG’s adverse reaction profile is similar to that of most chemotherapy treatments and is familiar to healthcare workers and generally quite manageable, particularly in oncology settings. Neutropenia occurred in 61% of patients treated with SG, while 47% of patients developed grade 3 to 4 neutropenia and 7% of patients developed febrile neutropenia.5 Dose modifications may be required in patients on SG who develop neutropenia.5 The SG prescribing information (PI) recommends withholding SG when a patient’s absolute neutrophil count drops to <1500/mm3 on day 1 of any cycle or their neutrophil count is <1000/mm3 on day 8 of any cycle.5 Granulocyte colony-stimulating factor was used in 47% of patients who received SG to restore neutrophil counts.5 Four percent of patients on SG permanently discontinued treatment due to neutropenia.5 Diarrhea occurred in 65% of patients treated with SG and 12% of patients had grade 3 to 4 diarrhea.5 The PI recommends withholding SG for grade 3 to 4 diarrhea at the time of scheduled treatment and resuming treatment when diarrhea resolves to grade ≤1.5 Diarrhea should also be evaluated for infectious causes, and if negative, loperamide should be initiated.5 Additional supportive measures, for example, oral fluid and electrolyte therapy, may also be employed as required.5

Nausea occurred in 66% of patients treated with SG and 4% of patients developed grade 3 nausea.5 Vomiting occurred in 39% of patients treated with SG and 3% developed grade 3 to 4 vomiting.5 The PI recommends premedicating with a 2- or 3-drug combination regimen (dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist) as well as other drugs as indicated.5 Before each dose of SG, premedication for the prevention of infusion reactions and prevention of chemotherapy-induced nausea and vomiting is also recommended.5 Premedicating with antipyretics, H1 and H2 blockers before infusion, and corticosteroids may be used for patients who had prior infusion reactions.5 The PI recommends withholding SG doses for grade 3 nausea or grade 3 to 4 vomiting at the time of scheduled treatment administration and resuming with additional supportive measures when resolved to grade ≤1.5 Additional antiemetics and other supportive measures may also be employed as clinically indicated.5 All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.5

Enfortumab vedotin and erdafitinib have safety profiles that are distinct and different from SG and/or chemotherapy treatment, and possibly less familiar to healthcare workers who may be less comfortable managing these treatments.


  1. Tagawa S, Balar A, Petrylak D, et al. ESMO 2019: phase 2 TROPHY-U-01 open label study of patients receiving sacituzumab govitecan with metastatic urothelial cancer after the failure of platinum-based regimens or immunotherapy. UroToday. www.urotoday.com/conference-highlights/esmo-2019/esmo-2019-bladder-cancer/115226-esmo-2019-phase-2-trophy-u-01-open-label-study-of-patients-receiving-sacituzumab-govitecan-with-metastatic-urothelial-cancer-after-failure-of-platinum-based-regimens-or-immunotherapy.html. Accessed February 7, 2022.
  2. Loriot Y, Balar A, Petrylak D, et al. TROPHY U-01 Cohort 1 final results: a phase II study of sacituzumab govitecan (SG) in metastatic urothelial (mUC) that has progressed after platinum (PLT) and checkpoint inhibitors (CPI). Ann Oncol. 2020;31(suppl_4):S1156.
  3. Tagawa S, Balar A, Petrylak D, et al. TROPHY-U-01: a phase II open label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors. J Clin Oncol. 2021;39:2474-2485.
  4. Gilead mUC CVA (Revised print). Trodelvy (Sacituzumab govitecan-hziy) in mUC. Accessed December 15, 2021.
  5. Product information (PI) for Trodelvy (sacituzumab govitecan-hziy). Indications and Usage. Updated April 2021. Accessed November 20, 2021.
Related Articles
Jelmyto First FDA-Approved Therapy for Low-Grade Upper-Tract Urothelial Cancer
Web Exclusives
Enfortumab Vedotin Promising Third-Line Option for Metastatic Urothelial Cancer After Checkpoint Inhibitor
December 2019 Vol 10, No 12
Patients with metastatic urothelial cancer receive first-line treatment with platinum-based chemotherapy and second-line treatment with a checkpoint inhibitor.
Sacituzumab, a Novel Antibody-Drug Conjugate, Shows Activity in Heavily Pretreated Patients with Urothelial Cancer
May 2019 Vol 10, No 5
Sacituzumab govitecan, a novel antibody-drug conjugate directed against Trop-2, induced response in nearly 33% of patients with heavily pretreated, relapsed, or refractory metastatic urothelial cancer.
Last modified: February 18, 2022

Subscribe to the Journal of Oncology Navigation & Survivorship®

To sign up for our print publication or e-newsletter, please enter your contact information below.

  • First Name *
    Last Name *
    Profession or Role
    Primary Specialty or Disease State

    Please enter your mailing address.

    Address Line 2
    Zip Code