Avelumab Outduels Supportive Care for Urothelial Cancer

Maintenance immunotherapy following chemotherapy may improve survival in advanced urothelial cancer, according to data that will be reported at the virtual 2020 American Society of Clinical Oncology (ASCO) Annual Meeting on May 31. In the phase III JAVELIN Bladder 100 trial, patients treated with the PD-L1 inhibitor avelumab (Bavencio; EMD Serono) plus best supportive care after first-line chemotherapy had significantly longer overall survival (OS) and progression-free survival (PFS) than those who received best supportive care alone, regardless of PD-L1 status.

Following diagnosis, advanced urothelial cancer is often treated with platinum-based chemotherapy, which elicits responses in about 65% to 75% of patients. However, many patients develop resistance to chemotherapy, causing their responses to be short-lived. Moreover, the disease progresses so quickly that only 25% to 55% of those patients are able to be treated with second-line immune checkpoint inhibitors—and even fewer benefit from these therapies.

The idea behind the JAVELIN trial is to prolong the effect of chemotherapy by giving patients avelumab immediately afterward, before their disease worsens. “It's essentially a first-line maintenance approach for patients with metastatic urothelial cancer who have not progressed on first-line chemotherapy,” said Thomas Powles, MD, of Barts Cancer Institute in London, UK, who will present the results.

The trial enrolled 700 patients with inoperable, locally advanced or metastatic urothelial cancer whose disease did not progress on cisplatin- or carboplatin-based chemotherapy; 51% of them had PD-L1–positive tumors. The 350 patients treated with avelumab plus best supportive care had a median OS of 21.4 months and a median PFS of 3.7 months, compared with 14.3 months and 2 months, respectively, in the rest of the patients, who received only best supportive care. This OS benefit was seen across subgroups, regardless of PD-L1 status, chemotherapy regimen, response to chemotherapy, or site of metastasis. Overall, 47.4% of patients receiving avelumab and best supportive care had side effects classified as grade 3 or higher, compared with 25.2% receiving only best supportive care. The most common serious side effects were urinary tract infections, anemia, hematuria, fatigue, and back pain.

Sumanta Pal, MD, of City of Hope Comprehensive Cancer Center in Duarte, CA, who was not connected to the trial, thinks the results “will certainly change the standard of care for patients with advanced bladder cancer.” He added that “for all patients that receive chemotherapy up front, maintenance therapy with avelumab becomes a mandate.” Moreover, he said researchers should consider incorporating maintenance checkpoint blockade into the design of future urothelial cancer trials with a chemotherapy arm.

“I consider it exciting data, and it helps us build on our knowledge base,” said Arlene Siefker-Radtke, MD, of The University of Texas MD Anderson Cancer Center in Houston, who was also not involved in the trial. She noted that until now, the only OS benefit for an immune checkpoint inhibitor in urothelial cancer was seen in the KEYNOTE-045 trial testing pembrolizumab (Keytruda; Merck) in patients whose disease had worsened on chemotherapy.

One question, she said, is how much patients will benefit from receiving avelumab as a maintenance therapy instead of receiving it after disease progression. However, she is even more interested in ongoing trials investigating other promising treatment strategies. “When I look toward the future, will it be giving chemotherapy followed immediately by a maintenance strategy? Will it be giving immunotherapy up front with chemotherapy? Immunotherapy with a novel agent? The field is so rich—there are a lot of neat compounds, a lot of combinations, and I think only time will tell.” –Catherine Caruso