Combining Chemotherapy With Checkpoint Inhibitors Extends Overall Survival in ES-SCLC

According to the results of a study presented at the IASLC’s 19th World Conference on Lung Cancer in Toronto, Canada, atezolizumab (anti-programmed death-ligand 1 [PD-L1] antibody) in combination with carboplatin plus etoposide in the first-line setting extended overall survival (OS) better than placebo and carboplatin plus etoposide in chemotherapy-naive participants with extensive-stage small cell lung cancer (ES-SCLC).

For IMpower133, patients were randomly selected to receive carboplatin and etoposide with either atezolizumab or placebo for four 21-day cycles in an induction phase and then to receive the same treatment during a maintenance cycle until toxicity was unacceptable, there was disease progression, or the treatment showed no additional benefit. Overall survival (OS) and progression-free survival (PFS) were the dual primary end points.

Approximately half of the patients were in the atezolizumab arm and the other half were in the placebo arm (201 and 202 individuals, respectively). At 13.9 months, the median OS was 12.3 months in those who received chemotherapy plus atezolizumab compared with 10.3 months in those who received chemotherapy plus placebo (hazard ratio for death, 0.70; 95% confidence interval [CI], 0.54-0.91; P =.007). Median PFS was 5.2 months and 4.3 months, respectively (hazard ratio for death, 0.77; 95% CI, 0.62-0.96; P =.02). According to a press release issued by Genentech in early September, “These are the first positive survival data from a phase 3 study with an immunotherapy-based combination in the initial treatment of ES-SCLC.”

And, according to an article published in The New England Journal of Medicine, the median OS in the atezolizumab group was 2 months longer than median OS in the placebo group. There were no differences in survival between treatment groups in patients with treated brain metastases, and the researchers noted there was an imbalance in the OS benefit based on patient age — older patients fared better than younger patients, which the researchers could not explain in simple terms.

Atezolizumab was definitely Genentech’s focus at the conference — 9 of the company’s presentations during the meeting featured data on the medication. The other Genentech medication that was specifically highlighted was entrectinib, an investigational agent for the treatment of locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer.

The benefits seen in the atezolizumab study suggest “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,” the researchers wrote.¹

Read more of Cancer Therapy Advisor‘s coverage of the IASLC 2018 meeting by visiting the conference page.

Reference

1. Horn L, Mansfield AS, Szczesna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer [published online September 25, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1809064