CHICAGO — The anti-PD-L1 immunotherapy atezolizumab (Tecentriq, Genentech), which recently made headlines when it was approved for second-line use in bladder cancer, appears to be effective in patients with previously untreated advanced disease, according to phase 2 data from the IMvigor210 trial.
Notably, patients in the study were relatively frail (especially with regard to impaired kidney function) and ineligible for treatment with standard cisplatin chemotherapy because of its toxicities, said lead investigator Arjun Vasant Balar, MD, director of genitourinary medical oncology at the NYU Perlmutter Cancer Center in New York City.
In the single-group trial of 119 patients with locally advanced or metastatic urothelial carcinoma, atezolizumab demonstrated a response rate of 24% (with 7% complete responses) and yielded a median survival of 14.8 months.
Dr Balar said that a median survival of 9 to 10 months would be expected in such patients, who would receive carboplatin or some other therapy because of their ineligibility for cisplatin.
He spoke during a press conference here at the American Society of Clinical Oncology 2016 Annual Meeting.
The estimated 12-month rate of overall survival was 57% in IMvigor210, and median follow-up was 14.4 months.
The findings could very well become more impressive with time. The current data are immature — 21 of the 28 responses were ongoing at the time of data cutoff, Dr Balar reported.
Nevertheless, "the survival we are seeing is very, very provocative," he asserted.
Furthermore, Dr Balar declared that atezolizumab, which was well tolerated in the study, makes a "compelling argument" to be a new standard of care in cisplatin-ineligible bladder cancer. This is significant; currently, many cases of bladder cancer (30% to 50%) go untreated because patients are not fit enough to endure cisplatin (or any other chemotherapy).
These data in the first-line setting of bladder cancer are also important for a number of other reasons, said Charles Drake, MD, PhD, associate director of the Bloomberg–Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University in Baltimore.
"Most of the immunotherapy work that has been done to date was in the second or third line, and we've wondered, as we moved these drugs to the first line, whether they would work the same," Dr Drake explained.
He pointed out that, in kidney cancer, limited patient data suggest that first-line anti-PD-1 is not as effective as second-line anti-PD-1.
The new atezolizumab data "strongly argue against that," said Dr Drake. The data used to approve the immunotherapy "are beautiful, in that they show that the response rate in the first line seems to be even better than in the second line," he noted.
In fact, he said, the efficacy of atezolizumab paves the way for that most desirable cancer treatment: one without chemotherapy.
"Going forward, we can envision having a regimen for bladder cancer for the first line that doesn't involve chemotherapy at all," he said, adding that such a regimen will likely be a combination, which is especially desirable for frail and sicker patients. Potential candidates for such a combination might include other immune checkpoint inhibitors such as nivolumab, durvalumab, and pembrolizumab, which are being tested in localized and advanced bladder cancer.
Study Details
Patients were enrolled in IMvigor210 if they were assessed to be cisplatin ineligible, which meant they had renal impairment (glomerular filtration rate >30 but <60 2.="" an="" at="" ecog="" grade="" hearing="" higher="" impairment="" least="" min="" ml="" nbsp="" neuropathy="" of="" or="" p="" performance="" peripheral="" status="">
Dr Balar and his colleagues describe atezolizumab as being "generally well tolerated" in their study abstract.
Treatment-related all-grade adverse events were seen in 64% of the patients, and grade 3/4 adverse events were seen in 12%. Related all-grade adverse events that affected at least 10% of the patients included fatigue, pruritus, and diarrhea. One grade 5 related adverse event occurred (sepsis). Only 3% of the patients experienced grade 3/4 immune-mediated adverse events.
Only 6% of patients discontinued treatment because of toxicity. In contrast, approximately 20% of bladder cancer patients being treated carboplatin-based chemotherapy regimens will discontinue, said Dr Balar.
The study was funded by Genentech, a member of the Roche Group. Dr Balar reports financial ties to industry, including Roche. Dr Drake has disclosed no relevant financial relationships.
American Society of Clinical Oncology (ASCO) 2016 Annual Meeting: Abstract LBA4500. To be presented June 5 2016.
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