Abstract
Results from a phase II study indicate that the PD-L1 inhibitor atezolizumab, recently approved for advanced bladder cancer that's refractory to standard platinum chemotherapy, is effective as first-line therapy for this disease. Durable responses to atezolizumab were seen in nearly a quarter of the study patients, who were all ineligible to receive cisplatin.
According to results from the phase II IMvigor 210 study, atezolizumab (Tecentriq; Genentech), the first-approved PD-L1 inhibitor, is effective in previously untreated patients with metastatic urothelial carcinoma who are ineligible for standard platinum-based chemotherapy. The findings were presented by Arjun Balar, MD, co-leader of the genitourinary cancer program at Perlmutter Cancer Center in New York, NY, during the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL, June 3–7.
First-line cisplatin offers a median survival of 12–15 months for patients with advanced bladder cancer. However, up to half are not eligible for this treatment due to additional medical problems; their median survival is 9–10 months, and there are no other standard options.
In May, the FDA conditionally approved atezolizumab as a second-line therapy for this disease, based on data from one of two cohorts in the IMvigor 210 study. At ASCO, Balar reported findings from the remaining cohort of 119 cisplatin-ineligible patients who received atezolizumab up front. The objective response rate was 24%, with 75% of these responses ongoing at a median follow-up of 14.4 months. The median overall survival was 14.8 months.
Atezolizumab was well tolerated, Balar said—its toxicity profile included hypothyroidism, liver abnormalities, skin rash, and diarrhea, most of which were resolved with steroids. Only 6% of participants stopped treatment due to side effects, compared to the typical discontinuation rate of 20% among patients on chemotherapy.
“It's essentially life-altering therapy for these patients,” Balar said. Based on the results of IMvigor 210, a phase III study of first-line atezolizumab for advanced bladder cancer is planned. Additional immune checkpoint inhibitors are also being investigated for this disease, including nivolumab (Opdivo; Bristol-Myers Squibb) and pembrolizumab (Keytruda; Merck). No one has done a head-to-head comparison of these inhibitors, Balar noted, and there's currently no reason to choose one over another for bladder cancer, aside from FDA approval status. Only atezolizumab has received the agency's nod so far, but other approvals are expected, he added.
“We welcome more of these types of agents into other tumors which are rare or have unmet needs,” said Edward Kim, MD, chair of solid tumor oncology and investigational therapeutics at the Carolinas HealthCare System's Levine Cancer Institute, which has more than 25 facilities across North Carolina and South Carolina.
Eventually, immunotherapies that target PD-1 or PD-L1 may replace chemotherapy in the treatment of bladder cancer, said Charles Ryan, MD, program leader of genitourinary medical oncology at the University of California, San Francisco.
“It is safe to envision a future where PD-L1 therapy could be used [up front], but we do need to do those studies” to prove effectiveness, he said. –Karen Weintraub
