He then placed the development of platinum chemotherapy for urothelial carcinoma within the context of other chemotherapy regimens as well as more recent developments in targeted and immunotherapy for this disease.
Drawing on a prior publication of his, Dr. Gust then delineated treatment options for advanced urothelial carcinoma based on medical eligibility for cisplatin therapy, as well as options for subsequent lines of therapy.
The three abstracts that Dr. Gust summarized were focused on combination therapies in various clinical settings with urothelial carcinomas. Combination therapies can have additive or synergistic effects if successful, and should not add significant toxicity for patients.
LBA27 presented data of induction avelumab followed by carboplatin/gemcitabine, then avelumab maintenance therapy as compared to carboplatin/gemcitabine alone in cisplatin-ineligible patients. The rationale for this trial comes from older datasets that suggested an improved response to chemotherapy after immune checkpoint blockade.
The data from this trial suggested that approximately 1 in 4 patients undergoing avelumab induction therapy had progressive disease or died, suggesting a critical missed opportunity for these patients. After this induction period, combination therapy performed similarly to chemotherapy alone but does not to seem to improve outcomes beyond chemotherapy.
In contrast, 704MO provided data on subgroup analysis from the JAVELIN Bladder 100 trial, which took a different approach from LBA27. IN JAVELIN Bladder 100, patients who had stable disease after induction platinum-based chemotherapy were randomized to avelumab maintenance versus supportive care, and a statistically significant improvement in overall survival was observed with avelumab maintenance therapy. Subgroup analysis confirmed this benefit trend across the pre-specified subgroups of carboplatin versus cisplatin, best-confirmed response, PD-L1 expression status, and metastatic sites. Overall, these two abstracts suggest that if staggered with chemotherapy, avelumab is better administered in the maintenance setting after disease stabilization with chemotherapy.
Primary resistance to immune checkpoint blockade is a significant clinical challenge. Abstract 705MO presented data looking at the multiple-tyrosine kinase inhibitor sitravatinib in combination with the anti-PD-1 drug nivolumab for patients with platinum-refractory advanced urothelial carcinoma, a strategy that may overcome primary immunotherapy resistance by decreasing the number of immunosuppressive cells in the tumor microenvironment. The combination of these two drugs resulted in a clinical benefit rate of 73% and ORR of 37%.
Together, these three abstracts highlight the work that remains to be done surrounding optimal management of advanced urothelial carcinoma especially with regards to combination treatment strategies.
Presented by: Killan M. Gust, MD, FEBU, Department of Urology, Medical University of Vienna, Austria
Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute at the European Society for Medical Oncology Virtual Congress, ESMO Virtual Congress 2020 #ESMO20, 18 Sept - 21 Sept 2020
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LBA27 Efficacy and Safety of Avelumab with Gemcitabine/Carboplatin (CG) vs CG Alone in Patients with Unresectable or Metastatic Urothelial Carcinoma Who are Ineligible to Receive Cisplatin-Based Therapy
704MO Avelumab First-Line Maintenance + Best Supportive Care vs. BSC alone with 1L chemotherapy for advanced urothelial carcinoma: Subgroup Analyses from JAVELIN Bladder 100
705MO Sitravatinib in Combination with Nivolumab Demonstrates Clinical Activity In Checkpoint Inhibitor Naïve, Platinum-Experienced Patients with Advanced or Metastatic Urothelial Carcinoma