ECC 2015: Atezolizumab in Locally Advanced or Metastatic Urothelial Carcinoma: Results of the IMvigor 210 Study
At the 2015 European Cancer Congress in Vienna, Austria, early results were announced (Abstract 21LBA) from a pivotal phase II study, IMvigor 210, of the investigational cancer immunotherapy atezolizumab (anti–PD-L1; MPDL3280A) in people with locally advanced or metastatic urothelial carcinoma. The study showed that atezolizumab had an objective response rate of 27% in patients with metastatic urothelial carcinoma whose disease had medium and high levels of PD-L1 expression and worsened after initial treatment. Of those who responded to atezolizumab, 92% continued to respond when the results were assessed. Median duration of response was not yet reached. Adverse events were consistent with those observed in previous studies.
“These results may represent the first major treatment advancement in advanced bladder cancer in nearly 30 years,” said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development at Genentech. “We are encouraged that responses to atezolizumab were ongoing in the large majority of people when the study results were assessed.”
These data will be submitted to global health authorities and to the U.S. Food and Drug Administration (FDA) under atezolizumab’s Breakthrough Therapy Designation for the treatment of people whose metastatic bladder cancer expresses PD-L1 (programmed cell death-ligand 1).
About the IMvigor 210 Study
These final results from the second cohort of the IMvigor 210 study were presented at the Congress by Jonathan E. Rosenberg, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center.
IMvigor 210 is an open-label, multicenter, single-arm phase II study that evaluated the safety and efficacy of atezolizumab in people with locally advanced or metastatic urothelial carcinoma, regardless of PD-L1 expression. People in the study were enrolled into one of two cohorts. Cohort 1 consisted of those who had received no prior therapies for locally advanced or metastatic urothelial carcinoma but who were ineligible for first-line cisplatin-based therapy; results for this cohort are not yet mature. Cohort 2, for which results were announced, included those whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen. People received a 1,200-mg intravenous dose of atezolizumab on day 1 of 21-day cycles until progressive disease (Cohort 1) or loss of clinical benefit (Cohort 2).
The primary endpoint of the study was objective response rate. Secondary endpoints included duration of response, overall survival, progression-free survival, and safety. Patients were selected by histology, prior lines of therapy, and PD-L1 expression on tumor-infiltrating immune cells using an investigational immunohistochemistry test, which is being developed by Roche Diagnostics. Median age was 66 years; 78% were male.
Significant objective response rate improvements were seen in IC2/3, IC1/2/3 and all-comer patients (P < 0.01). There were 12 complete responses and 35 partial responses; 15 additional unconfirmed RECIST v1.1 complete response/partial responses were seen. Responses occurred in all PD-L1 subgroups, and objective response rate improved with increasing PD-L1 expression; median duration of response was not yet reached with a minimum follow-up of 24 weeks. Of the 47 responding patients, 43 were still responding at data cutoff.
Although survival data are immature, a longer overall survival was seen in patients with higher PD-L1 expression. Median survival follow-up was 7 months ([range, 0–11], 142 events). Median treatment duration was 12 weeks (0–46). A Table with more study information is viewable here.
Safety was assessed in 311 people, and adverse events were consistent with those observed in previous studies. There were no treatment-related deaths. Fifteen percent of people experienced grade 3-4 treatment-related adverse events, and 4% of people experienced a grade 3-4 immune-related adverse event. The most common grade 3-4 treatment-related adverse events were fatigue, decreased appetite, pyrexia, arthralgia, dyspnea, anemia, alanine transaminase increase, pneumonitis, hypertension, and hypotension.
In addition to IMvigor 210, Genentech has an ongoing randomized phase III study, IMvigor 211, comparing atezolizumab with standard-of-care chemotherapy in people who have relapsed metastatic urothelial carcinoma that worsened after initial treatment.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
