Adding Atezolizumab to Chemotherapy Significantly Improves Survival in SCLC

Interim results from a recent clinical trial reveal that the addition of atezolizumab to chemotherapy in the first-line treatment of patients with extensive-stage small-cell lung cancer significantly improved overall survival (OS) and progression-free survival (PFS) when compared with chemotherapy alone (N Engl J Med. 2018 Sep 25. Epub ahead of print).

“Clinical activity of immunotherapies has been observed in patients with refractory or metastatic small-cell lung cancer; however, a phase 2 single-group study of maintenance pembrolizumab and a phase 3 study of ipilimumab plus chemotherapy showed no improved efficacy in the first-line treatment of extensive-stage small-cell lung cancer,” explained lead investigator Leora Horn, MD, MSc, FRCPC, Ingram Associate Professor of Cancer Research, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues.

Alternatively, atezolizumab, an anti–programmed death ligand 1 (PD-L1) drug that inhibits PD-L1–programmed death 1 (PD-1) and PD-L1–B7-1 signaling, has been shown to have an acceptable side-effect and safety profile, as well as promising durability of response in patients with relapsed or refractory small-cell lung cancer.

The multinational, double-blind, placebo-controlled Impower133 clinical trial was conducted to assess the safety and efficacy of using atezolizumab with carboplatin and etoposide in the first-line treatment of patients with extensive-stage small-cell lung cancer.

The IMPOWER133 Clinical Trial

The phase 1/3 IMpower133 trial included 403 treatment-naïve patients with extensive-stage small-cell lung cancer who met the study’s eligibility criteria. These criteria included having histologically or cytologically confirmed extensive-stage small-cell lung cancer per the Veterans Administration Lung Study Group staging system and an Eastern Cooperative Oncology Group performance status score 0 or 1.

Patients were randomized in a 1:1 ratio to receive an induction regimen of carboplatin and etoposide with atezolizumab (n = 201) or placebo (n = 202). The induction phase was followed by maintenance therapy with atezolizumab or placebo—administered in accordance with what the patient was randomized to receive during the induction phase—until unacceptable toxicity or disease progression occur.

Significant Improvements in Survival

The median follow-up was 13.9 months, as of the time of data cutoff. The median overall survival rates for patients in the atezolizumab and placebo arms were 12.3 months and 10.3 months, respectively, and the median progression-free survival rates were 5.2 months and 4.3 months, respectively. Disease progression or death occurred in 171 (85.1%) patients in the atezolizumab arm and 189 (93.6%) patients in the placebo arm.

According to Dr Horn and colleagues, there were no new safety findings observed; the safety profile of atezolizumab plus carboplatin and etoposide was consistent with the profiles previously reported for each of the individual drugs.

“[T]he current trial showed a significant improvement in progression-free survival and overall survival with the addition of atezolizumab to chemotherapy as first-line treatment,” Dr Horn and colleagues said.

“This suggests that combining checkpoint inhibition with cytotoxic therapy during induction may be beneficial and potentially necessary to improve overall survival beyond that seen with the current standard of care, and thus it may be a preferred treatment approach over maintenance checkpoint-inhibitor therapy alone,” they concluded, adding that it is important for future trials to directly compare the 2 treatment approaches.—Hina Khaliq