Jason M. Broderick and Kristie Kahl
The FDA has granted a priority review designation to a supplemental biologics license application (sBLA) for Tecentriq (atezolizumab) for use in combination with carboplatin and etoposide for the frontline treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).
The sBLA is based on the phase 3 IMpower133 study, in which adding Tecentriq to standard upfront carboplatin and etoposide significantly prolonged survival in patients with ES-SCLC. The FDA action date for a decision on the sBLA is March 18, 2019.
After a median follow-up of 13.9 months, the median overall survival (OS) in IMpower133 was 12.3 months in the Tecentriq arm compared with 10.3 months in the placebo arm — a 30 percent reduction in the risk of death. OS events occurred in 51.7 percent of the Tecentriq arm and 66.3 percent of the control arm.
Median progression-free survival (PFS) was 5.2 months in the Tecentriq group compared with 4.3 months in the placebo. Tecentriq was associated with a higher six-month PFS rate (30.9 percent vs. 22.4 percent), and a more than doubling 12-month PFS rate (12.6 percent vs 5.4 percent) compared with placebo.
“It’s been more than 20 years since there has been a new initial treatment option for extensive-stage small cell lung cancer that delivers a clinically meaningful survival benefit,” Sandra Horning, M.D., chief medical officer and head of Global Product Development, Genentech (Roche), the manufacturer of Tecentriq, said in a statement.
“We are working closely with the FDA to bring this Tecentriq-based regimen to people with this difficult-to-treat type of lung cancer as soon as possible,” added Horning.
The global, double-blind, randomized, placebo-controlled phase 1/3 IMpower133 trial evaluated the efficacy and safety of first-line Tecentriq as adjunctive therapy to standard of care, combination carboplatin and etoposide, in 403 treatment-naïve patients with ES-SCLC.
Results from the study were presented at the 19th World Conference on Lung Cancer. The results were simultaneously published in the New England Journal of Medicine
All patients received four 21-day cycles of carboplatin AUC 5 mg/mL/min IV on day one and 100 mg/m2
etoposide IV on days 1 through 3. Patients were also randomized 1 to 1 to receive either concurrent Tecentriq at 1200 mg IV on day 1 (201 patients) or placebo (202 patients) during the induction phase. Treatment was followed by maintenance therapy with Tecentriq or placebo, according to the previous random assignment, every three weeks until progressive disease or loss of clinical benefit.
Investigator-assessed PFS and OS in the intention-to-treat population served as the primary endpoints. Secondary endpoints included objective response rate (ORR), duration of response, and safety.
Age, demographics, and smoking status were representative of the disease: median age was 64 years (range, 26-90) in both the Tecentriq and placebo groups, and the majority were male (64 percent vs 65 percent, respectively), white (81 percent vs 79 percent), and former smokers (58.7 percent vs 61.4 percent). The Tecentriq arm included 17 patients (8 percent) with brain metastases and 77 (38 percent) with liver metastases; while the placebo group consisted of 9 percent and 36 percent, respectively.
The median duration of treatment with Tecentriq was 4.7 months, with a median of 7 doses received. The investigators saw no major difference in ORR between arms (60.2 percent vs 64.4 percent, respectively) or in median duration of response (4.2 vs 3.9 months).
Tecentriq demonstrated superior 6-month (32.2 percent vs 17.1 percent) and 12-month (14.9 percent vs 6.2 percent) event-free rates. Eighteen patients treated with concurrent Tecentriq had ongoing responses compared with only 7 patients in the control arm.
The safety profile of the regimen appeared consistent with the previously reported safety profile of the individual agents, with no new findings observed.
The most common grade 1/2 treatment-related AEs among the Tecentriq and placebo arms included neutropenia (13.1 percent vs 10.2 percent, respectively), anemia (24.7 percent vs 20.9 percent), decreased neutrophil count (3.5 percent vs 6.1 percent), thrombocytopenia (6.1 percent vs 7.1 percent), and leukopenia (7.6 percent vs 5.1 percent).
Immune-related adverse events (IRAEs) were more common with Tecentriq compared with placebo (39.9 percent vs 24.5 percent). The most common grade 1 or 2 IRAEs among the Tecentriq and placebo arms included rash (16.7 percent vs 10.2 percent, respectively), hepatitis (5.6 percent vs 4.6 percent), infusion-related reactions (3.5 percent vs 4.6 percent), pneumonitis (1.5 percent vs 1.5 percent) and colitis (0.5 percent vs 0 percent).
Tecentriq has approved FDA indications for non–small cell lung cancer and urothelial carcinoma.
This article originally appeared on onclive.com as "FDA Grants Atezolizumab Regimen Priority Review for Frontline SCLC."