Atezolizumab combined with carboplatin/etoposide represents a new standard of care for first-line treatment of extensive-stage small cell lung cancer (ES-SCLC), according to results from the phase 3 IMpower133 trial presented at the IASLC 19th World Conference on Lung Cancer.
Atezolizumab plus carboplatin/etoposide improved overall survival and progression-free survival. At a median follow-up of 13.9 months, median overall survival was 12.3 months in the atezolizumab group versus 10.3 months in the placebo arm, representing a 30% reduction for the likelihood of death (P = .007). Median progression-free survival was 5.2 months and 4.3 months, respectively (P = .02)
“IMpower133 is the first trial in more than 20 years to show a clinically meaningful improvement in overall survival compared with the current standard of care in first-line ES-SCLC,” stated senior author of this study Stephen Liu, MD, Georgetown University, Washington, DC. “These findings suggest that atezolizumab plus carboplatin/etoposide represents a new treatment for first-line treatment of ES-SCLC.”
Hold Your Horses
Although formal discussant Natasha B. Leighl, MD, Princess Margaret Cancer Center, Toronto, Canada, acknowledged that an improvement in survival in ES-SCLC is an achievement, she was more cautious about whether this approach would be widely adopted, mainly due to a modest 2-month gain in survival weighed against the considerable cost of treatment with immunotherapy.
“Is the benefit of atezolizumab during induction or in maintenance? Is a 2-month gain in survival clinically significant? We could say that immunotherapy has lots of financial toxicity, maybe grade 3 or 4. So is this small clinical benefit worth the cost of treatment?” she asked listeners.
“The economic hurdle will depend on regulators. But this is the first positive randomized controlled trial in SCLC, with a 30% survival improvement,” Dr Leighl said. “We still need new treatments for ES-SCLC.”
IMpower133 Description
The randomized, placebo-controlled, double-blind phase 3 IMpower133 study enrolled 403 patients with untreated measurable ES-SCLC at 106 sites in 21 countries.
Study participants were randomized 1:1 to receive 4 cycles of carboplatin/etoposide with either 1200-mg atezolizumab on day 1 of each cycle or placebo, followed by maintenance therapy with atezolizumab or placebo according to previous randomization until disease progression or toxicity. Continuation of treatment was allowed after progression if there was evidence of clinical benefit. Tissue samples were requested, but not mandated, for all patients.
“Atezolizumab did not interfere with the ability to give 4 cycles of standard chemotherapy,” Dr Liu said.
Atezolizumab had a consistent benefit over placebo in all subgroups, including sex, age, ECOG score (0 vs 1), presence of liver metastases, and level of tumor mutation burden.
Although objective response rates were similar in the 2 arms, approximately 3 times as many patients in the atezolizumab arm had an ongoing response: ~15% versus 4% for placebo. Tumor mutation burden did correlate with response to atezolizumab.
The safety profiles of all 3 drugs were similar to those previously reported, and no new safety signals emerged. The frequency of adverse events, including hematologic events, was similar in the 2 arms, except that immune-related adverse events were more common in patients who received atezolizumab (39.9% vs 24.5% for placebo).
Impower133 was funded by F. Hoffman-La Roche, Ltd.