Immunotherapy Provides Long-Awaited Progress in Small Cell Lung Cancer

Immunotherapy is showing progress in the treatment of extensive-stage small cell lung cancer (SCLC) — a setting that has not seen clinically meaningful improvement in overall survival in about two decades.

According to the American Cancer Society, extensive stage SCLC is a disease that has spread too far for surgery or radiation therapy to be useful for initial treatment, and therefore, chemotherapy has been the standard of care for these patients.

“SCLC is an area where we’ve seen very little progress in nearly 20 years. For patients with extensive-stage disease, platinum etoposide has continued to remain the standard of care, and improvements to that have not come, despite a number of efforts to add on to that backbone,” said Suresh Ramalingam, M.D., deputy director of the Winship Cancer Institute of Emory University.

Immunotherapy has been much slower to move into the SCLC space compared with non-small cell lung cancer (NSCLC), due, in part, to SCLC’s typically low expression of PD-L1, the protein that checkpoint blockades block, in turn making these therapies less effective.

But now, results from the Impower133 trial, which was recently presented at the International Association for the Study of Lung Cancer 19th World Conference on Lung Cancer — held in Toronto from Sept. 23 to 26 – are changing that.

The global, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of the immunotherapy agent Tecentriq plus carboplatin etoposide for patients with extensive-stage SCLC who have had no prior treatment.

All patients were treated with 21-day cycles of chemotherapy, and were also randomized 1:1 to receive either concurrent Tecentriq (atezolizumab; 201 patients) or placebo (202 patients) 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.

At a median follow-up of 13.9 months, the Tecentriq group experienced superior overall survival (12.3 months vs. 10.3 months, respectively) and progression-free survival (5.2 months vs. 4.3 months) compared to the placebo group.

“What we heard just about a month ago at the World Conference on Lung Cancer, and in our published paper in the New England Journal of Medicine, is that for the first time, we have an advance,” Ramalingam said.

While the Impower133 results are setting the stage for landmark change in the frontline setting for SCLC, another immunotherapy agent — Opdivo (nivolumab) — was approved this summer for patients with small cell lung cancer whose disease progressed after two or more previous lines of therapy.