FDA Approves Tecentriq Plus Chemo for Small Cell Lung Cancer

The Food and Drug Administration (FDA) has granted an approval to the combination of Tecentriq (atezolizumab) with carboplatin and etoposide for the frontline treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).

The approval is based on findings from the phase 3 IMpower133 study, which demonstrated that the addition of Tecentriq to carboplatin and etoposide led to a significant improvement in overall survival (OS) in patients with ES-SCLC.

"Tecentriq is the first cancer immunotherapy approved for the initial treatment of extensive-stage small cell lung cancer, which is especially difficult to treat," said Sandra Horning, M.D., chief medical officer and head of Global Product Development, Genentech (Roche), the manufacturer of the PD-L1 inhibitor. "Until now, there have been limited treatment advances for this disease, and we are excited to bring a potential new standard of care to patients that has been shown to improve survival compared to chemotherapy."

Data showed that after a median follow-up of 13.9 months, the median OS in IMpower133 was 12.3 months in the Tecentriq arm compared with 10.3 months in the carboplatin/etoposide and placebo arm, leading to a 30 percent reduction in the risk of death.

Moreover, the median progression-free survival (PFS) was 5.2 months in the Tecentriq arm compared with 4.3 months in the placebo group.

The international, double-blind, randomized, placebo-controlled phase 3 IMpower133 trial evaluated the efficacy and safety of frontline Tecentriq added to the standard of care, combination carboplatin and etoposide, in 403 treatment-naïve patients with ES-SCLC.

All patients received four 21-day cycles of carboplatin AUC 5 mg/mL/min IV on day 1 and 100 mg/m2 etoposide IV on days 1 through 3. Patients were also randomized 1:1 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 seven 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).

Results from the study were presented at the 19th World Conference on Lung Cancer.2 The results were simultaneously published in the New England Journal of Medicine. Additional data showed that OS events occurred in 51.7 percent of the Tecentriq arm and 66.3 percent of the control arm. Tecentriq was associated with a higher 6-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.

The PD-L1 inhibitor 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.

Regarding safety, the profile of the regimen was consistent with prior studies of the individual agents, with no new findings observed. The most common all-grade adverse events (AEs; ≥20 percent) in those who received Tecentriq /chemotherapy were fatigue/asthenia (39 percent), nausea (38 percent), alopecia (37 percent), decreased appetite (27 percent), constipation (26 percent) and vomiting (20 percent).

Additionally, 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). Serious AEs occurred in 37 percent of patients who received Tecentriq plus chemotherapy compared with 35 percent of those on chemotherapy alone.

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).

"Extensive-stage small cell lung cancer is a highly aggressive form of lung cancer, which until now, has seen limited treatment advances over the last 20 years," said Andrea Ferris, president and CEO of LUNGevity Foundation. "Today's approval of Tecentriq is an important step forward in ensuring that people across the spectrum of lung cancer types have effective new therapies."

This article was originally published on OncLive as "FDA Approves Atezolizumab Regimen for Frontline Small Cell Lung Cancer."