Atezolizumab Combo Improves Survival in Frontline SCLC

Sandra Horning, MD

Combining frontline atezolizumab (Tecentriq) with chemotherapy improved overall survival (OS) and progression-free survival (PFS) compared with chemotherapy alone in patients with extensive-stage small cell lung cancer (ES-SCLC), meeting the coprimary endpoints of the phase III IMpower133 trial.

Genentech (Roche), the manufacturer of the PD-L1 inhibitor, reported in a press release that results from this interim analysis will be presented at an upcoming medical conference. The company also noted that adverse events were consistent with single-agent use of the treatments, and no new safety signals emerged with the combination.

“These are the first positive phase III survival results for any immunotherapy-based combination in the initial treatment of extensive-stage small cell lung cancer, a particularly difficult-to-treat type of disease,” Sandra Horning, MD, chief medical officer and head of Global Product Development, Genentech, said in a statement.

“The clinically meaningful results from the IMpower133 study add to the growing body of evidence demonstrating that Tecentriq-based combinations may be an effective treatment for different types of advanced lung cancer. We look forward to working with health authorities globally to bring this potential treatment option to people with this type of disease as soon as possible,” added Horning.

The multicenter, double-blinded phase III IMpower133 trial randomized 403 chemotherapy-naïve patients with ES-SCLC in a 1:1 ratio to carboplatin and etoposide plus either atezolizumab or placebo. Patients received induction treatment for four 21-day cycles followed by maintenance with atezolizumab or placebo until symptomatic deterioration or disease progression.

While this is the first trial in the SCLC setting, several other IMpower trials have demonstrated the efficacy of atezolizumab in non—small cell lung cancer (NSCLC). Findings from the phase III IMpower131 trial presented at the 2018 ASCO Annual Meeting showed that the addition of atezolizumab to frontline carboplatin and nab-paclitaxel (Abraxane) delayed the risk of progression or death by 29% compared with chemotherapy alone for patients with advanced squamous NSCLC.

At a median follow-up of 17.1 months, the median PFS was 6.3 months (95% CI, 5.7-7.1) with the addition of atezolizumab versus 5.6 months (95% CI, 5.6-5.7) with chemotherapy alone (HR, 0.71; 95% CI, 0.60-0.85; P = 0.0001). The 12-month PFS rates were 24.7% versus 12.0%, respectively.

In the phase III IMpower150 trial, also presented at the 2018 ASCO Annual Meeting, the combination of atezolizumab, bevacizumab (Avastin), carboplatin, and paclitaxel (ABCP) reduced the risk of death by 22% compared with bevacizumab and chemotherapy (BCP) in patients with advanced wild-type NSCLC.

The median OS with the addition of the PD-L1 inhibitor atezolizumab was 19.2 months (95% CI, 17.0-23.8) compared with 14.7 months (95% CI, 13.3-16.9) in the BCP arm (HR, 0.78; 95% CI, 0.64-0.96; P = .0164). The 24-month OS rate with atezolizumab was 43% compared with 34% for BCP. ABCP also improved median PFS by 1.5 months compared with BCP (8.3 vs 6.8 months; HR, 0.59; 95% CI, 0.50-0.70; P <.0001).

Based on data from the IMpower150 trial, the FDA is currently reviewing a supplemental new drug application for the ABCP regimen in nonsquamous metastatic NSCLC. The FDA is scheduled to make its decision on the sBLA by September 5, 2018.

Genentech also announced in May 2018 that in the phase III IMpower130 study, adding atezolizumab to nab-paclitaxel and carboplatin in the frontline setting significantly improved OS in patients with advanced nonsquamous non—small cell lung cancer. The company plans to share the study data at an upcoming oncology meeting.

References

1. Jotte RM, Cappuzzo F, Vynnychenko I, et al. IMpower131: Primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC. J Clin Oncol. 2018;36 (suppl; abstr LBA9000).
2. Socinski MA, Jotte R, Cappuzzo F, et al. Overall survival (OS) analysis of IMpower150, a randomized Ph 3 study of atezolizumab (atezo) chemotherapy (chemo) ± bevacizumab (bev) vs chemo + bev in 1L nonsquamous (NSQ) NSCLC. J Clin Oncol. 2018;36 (suppl; abstr 9002).