Immunotherapy Moves Into Small Cell Lung Cancer Space

While the non-small cell lung cancer (NSCLC) treatment landscape has experienced landmark changes thanks, in part, to the addition of immunotherapy, therapies for small cell lung cancer (SCLC) have not been advancing as quickly. However, the future of immunotherapy for the treatment of SCLC is bright, according to Paul A. Bunn Jr., M.D.

“Immunotherapy is going to be a part of the treatment and there is going to be a resurgence of interest and, hopefully, more people going on trials,” Bunn, the James Dudley Chair in Lung Cancer Research at the University of Colorado Cancer Center, said in an interview with OncLive, a sister publication of CURE.

He added that the main types currently being investigated are checkpoint blockades that bind to and block PD-1 or PD-L1 function, which then alerts the immune system to attack cancer cells. In particular, Yervoy (ipilimumab), Keytruda (pembrolizumab) and Tecentriq (atezolizumab) are showing promise for patients with SCLC.

Currently, per National Comprehensive Cancer Network (NCCN) guidelines, patients with SCLC can be treated with Opdivo (nivolumab), Opdivo plus Yervoy or single-agent Keytruda after treatment with chemotherapy.

Just last month, the Food and Drug Administration (FDA) granted an accelerated approval to Opdivo to be used as single agent to treat patients with SCLC with disease progression after platinum-based chemotherapy and one other line of therapy. The approval was based off the CheckMate-032 trial, in which those who received Opdivo demonstrated an objective response rate of 12 percent and experienced a median duration of response for 17.9 months.

While NSCLC tumors tend to have higher PD-L1 expression — making them more likely to be receptive to checkpoint blockades – SCLC tumors tend to have low expression, which has sent researchers looking for a better biomarker to help determine treatments for these patients.

“One that has been suggested is tumor mutation burden. Small cell cancers, since they’re all in smokers, have a higher (tumor mutation burden) in general,” Bunn said. “There’s some evidence that (tumor mutation burden) might be a good biomarker, especially for the addition of CTLA-4 inhibitors.”

In addition to limited biomarkers, when asked about other challenges that are unique to the treatment of SCLC, Brunn had three in mind. “First, all patients with SCLC are heavy smokers so they have a lot of comorbid diseases, so anything with toxicity will be [of higher grade] in SCLC.”

“Second, since smoking has been declining in the United States over the past 20 years, the number of SCLC cases has been declining,” he added. “Third, because we haven't had any treatment advances and the same chemotherapy has been standard, many people in the community keep these patients and don't refer them to clinical trials. Finally, after 20 or 30 years, that's beginning to change, albeit slowly.”

Once researchers and practitioners grasp the best way to use these agents for patients with SCLC, Bunn is hopeful that they could bring monumental change.

“It’s likely that immunotherapy will be used in the first-line setting. It may be that we need to measure (tumor mutation burden) and consider combinations of immunotherapies, but that remains to be determined,” he said. “I’m very optimistic that checkpoint inhibitors will improve survival in SCLC to the same extent that they do in NSCLC.”