ASCO 2019: A Pilot Safety Study of Gemcitabine and Cisplatin with Atezolizumab as First-Line Therapy in Patients with Metastatic Urothelial Cancer

Chicago, IL (UroToday.com) Combination chemo-immunotherapy has led to benefits in overall survival over chemotherapy alone for both lung cancer and breast cancer. In lung cancer, KEYNOTE-189 showed that patients receiving pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab had improved overall survival and progression-free survival over chemotherapy alone.1 In IMpassion 130, patients with untreated metastatic triple-negative breast cancer were randomly assigned to receive atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel. Those receiving chemoimmunotherapy had a median progression-free survival of 7.2 months with atezolizumab plus nab-paclitaxel, as compared with 5.5 months (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.69 to 0.92; P=0.002).2 This study examines a similar strategy of chemoimmunotherapy for patients with metastatic urothelial cancer (mUC).

This abstract provides data on 10 patients receiving GC+A. Baseline characteristics are shown below.
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The primary endpoint was safety, as assessed by the dose-limiting toxicity rate during the first cycle for the first 6 patients. There were no dose-limiting toxicities (DLTs) during the first cycle. Grade 3/4 hematologic adverse events such as neutropenia (7/10) and anemia (6/10) occurred in the majority of patients. Only 1 patient discontinued study treatment due to treatment-related adverse events including grade 4 encephalopathy and grade 3 polyneuropathy.
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Of the 10, 9 patients achieved an objective response, of which 5 eventually had progressive disease.
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Two patients have had very durable responses, with 1 patient without progression at 25 months and one patient status post consolidation surgery with a pathologic complete response (CR) and remains disease-free at 21 months.
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After a median follow up of 23.8 months, the median PFS was 10.7 months and median OS has not yet been reached.
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The results of these first 10 patients demonstrate that GC+A is relatively tolerable for patients with only one discontinuation due to toxicity. The neoadjuvant study with GC+A is ongoing. A larger single arm study had been reported for the combination of gem/cis plus ipilimumab and a similarly high number of grade 3/4 AEs were reported there as well (81%). Two large phase III studies, KEYNOTE 361 (NCT02853305) and IMvigor 130 (NCT02807636), are now underway to evaluate chemoimmunotherapy vs. chemotherapy for mUC.

Presented by: Samuel Aaron Funt, MD, Memorial Sloan Kettering, New York, NY 

Written by: Jason Zhu, MD, Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

References:
  1. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. New England journal of medicine 2018;378:2078-92.
  2. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. New England Journal of Medicine 2018;379:2108-21.
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