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Treating Cisplatin-Ineligible Metastatic Urothelial Carcinoma: Sarmad Sadeghi, MD, PhD

Sarmad Sadeghi, MD, PhD

For many patients with metastatic urothelial carcinoma, cisplatin-containing chemotherapy is not an option; alternative treatments are greatly needed. Recently, the phase 2 California Cancer Consortium trial, led by Sarmad Sadeghi, MD, PhD, reported that a combined regimen of gemcitabine (Gemzar®, Eli Lilly) and eribulin (Halaven®, Eisai Inc.) demonstrates efficacy in cisplatin-ineligible patients with metastatic urothelial carcinoma. In this interview with i3 Health, Dr. Sadeghi discusses the importance of the trial's results and the latest advances in the treatment of metastatic urothelial carcinoma.

Can you comment on the significance of your study's findings concerning gemcitabine/eribulin in cisplatin-ineligible patients with metastatic urothelial carcinoma?

Sarmad Sadeghi, MD, PhD: This study demonstrates that the combination of gemcitabine and eribulin has activity in the treatment of metastatic urothelial carcinoma. The treatment of patients who are not eligible for cisplatin has been an area of unmet need for a very long time and remains a significant challenge for patients and their treating physicians, even with the advent of immunotherapy.

How does the gemcitabine/eribulin regimen compare with other treatment options for cisplatin-ineligible patients with metastatic urothelial carcinoma, in terms of both safety and efficacy?

Dr. Sadeghi: For cisplatin-ineligible patients, options are very limited. The gemcitabine/carboplatin regimen is widely used, with a response rate of 41% and severe acute toxicity of 9.3%, as reported in the European Organisation for Research and Treatment of Cancer (EORTC) Study 30986. For those who express programmed death-ligand 1 (PD-L1) on their tumor's infiltrating immune cells, immunotherapy with anti­–programmed cell death protein 1 (PD-1)/PD-L1 is another option, with responses seen in 28% to 37% of PD-L1–positive patients who were cisplatin ineligible in the IMVigor210 and Keynote-052 trials. Our trial is small, but it shows a response rate of 50% that compares favorably with those of gemcitabine/carboplatin and anti–PD-1/PD-L1 antibodies. The toxicity profile is also very reasonable.

Is further research underway for gemcitabine/eribulin in this patient population?

Dr. Sadeghi: A phase 3 trial with eribulin is in development through the SWOG Cancer Research Network (formerly Southwest Oncology Group) and in collaboration with other oncology cooperative groups and the National Clinical Trial Network. This phase 3 study (SWOG s1937) will test the role of eribulin in previously treated patients with urothelial carcinoma.

What advice can you give to oncologists and urologists treating patients with metastatic urothelial carcinoma?

Dr. Sadeghi: The options for metastatic urothelial cancer are expanding, as evidenced by the success of PD-1/PD-L1 antibodies. We expect the first antibody-drug conjugate, enfortumab vedotin, to become available in this disease for patients treated with immunotherapy. In clinical practice, agents with different mechanisms of action are needed to maximize outcomes for this groups of patients, who have historically fared poorly.

About Dr. Sadeghi

Sarmad Sadeghi, MD, PhD, is an Assistant Professor of Clinical Medicine at the University of Southern California (USC) Keck School of Medicine and the USC Norris Comprehensive Cancer Center. An oncologist, Dr. Sadeghi also holds a PhD in Public Health Management and Policy Sciences. He is a California Cancer Consortium Distinguished Faculty Member.

For More Information

Sadeghi S, Groshen SG, Tsao-Wei DD, et al (2019). Phase II California Cancer Consortium trial of gemcitabine-eribulin combination in cisplatin-ineligible patients with metastatic urothelial carcinoma: final report (NCI-9653). J Clin Oncol. [Epub ahead of print] DOI:10.1200/JCO.19.00861

Balar AV, Castellano D, O'Donnell PH, et al (2017). First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol, 18(11):1483-1492. DOI:10.1016/S1470-2045(17)30616-2

Balar AV, Galsky MD, Rosenberg JE, et al (2017). Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet, 389(10064):67-76. DOI:10.1016/S0140-6736(16)32455-2

De Santis M, Bellmunt J, Mead G, et al (2012). Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol, 30(2):191-199. DOI:10.1200/JCO.2011.37.3571


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