Elizabeth Plimack, MD, chief, Division of Genitourinary Medical Oncology, director, Genitourinary Clinical Research, Fox Chase Cancer Center, discusses practice-changing studies for genitourinary cancers presented at the 2019 ASCO Annual Meeting.
Preliminary data from EV-201, which evaluated 125 patients, showed that enfortumab vedotin monotherapy has a clinically meaningful overall response rate (ORR) of 42% for those with locally advanced or metastatic urothelial cancer previously treated with platinum and immune checkpoint inhibitors. Patients received 1.25 mg of enfortumab vedotin on days 1, 8, and 15 of each 28-day cycle. Treatment-related adverse events (AEs) were fatigue (50%), alopecia (48%), decreased appetite (41%), rash (48%), and peripheral neuropathy (50%). Enfortumab vedotin met a high unmet need for patients who progressed on or after platinum and/or a checkpoint inhibitor. According to Plimack, enfortumab vedotin is slated for approval by the FDA depending on results from an ongoing phase III trial to compare enfortumab vedotin with chemotherapy.
Erdafitinib (Balversa) is an “exciting” new drug for bladder cancer because, according to Plimack, “It is the first targeted therapy to a specific alteration in the tumor that we’ve had in bladder cancer.” It targets FGFR3, and the drug was approved on that basis. However, FGFR3 is present in the way it needs to be for erdafitinib to work in 10% of patients. Erdafitinib brought molecular testing to the forefront, which Plimack believes should be standard of care for patients with bladder cancer to find out if erdafitinib will be an option for them after platinum-based chemotherapy and checkpoint inhibitors.
For renal cell carcinoma (RCC), there were two prominent studies—the KEYNOTE-426 and JAVELIN Renal 100 trials—which looked at combining frontline immunotherapy with axitinib (Inlyta). The phase III KEYNOTE-426 study compared pembrolizumab (Keytruda) plus axitinib versus sunitinib (Sutent) as first-line therapy for locally advanced or metastatic renal cell carcinoma. Of 861 randomized patients, in which 432 received pembrolizumab plus axitinib and 429 received sunitinib, pembrolizumab/axitinib had greater 1-year overall survival (OS) rates (89.9% vs 78.3%), improved median progression-free survival (15.1 vs 11.1 months), and higher ORR (59.3% vs 35.7%). Data suggest pembrolizumab plus axitinib should be the new standard of care for patients with previously untreated, advanced or metastatic clear cell RCC.
The phase III JAVELIN Renal 101 study compared avelumab (Bavencio) plus axitinib against sunitinib in advanced renal cell carcinoma (aRCC). The study found gene mutations such as CD1631L, PTEN, DNMT1 affected PFS outcomes, demonstrating the importance of molecular testing. The JAVELIN Renal 101 study gave physicians information about how to personalize treatment methods for patients with advanced RCC.