Basics of Immunotherapy in SCLC

In a session presented at the 2020 Personalized Therapies in Thoracic Oncology virtual meeting, Stephen V. Liu, MD, Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C, shared insight on immunotherapy treatment for small-cell lung cancer (SCLC). 

Dr Liu discussed the natural history of SCLC based on early cancer studies, specifically the poor efficacy of chemotherapy and lack of alternatives for decades until they switched to immunotherapy.

“Despite these limitations and relatively poor survival for chemotherapy, it was standard care for decades. There were dozens of phase 3 trials that attempted to improve that standard and simply failed. There was tremendous promise with immunotherapy, this had transformed the treatment for many cancers, including non-small cell lung cancer,” Dr Liu explained.

“There seemed to be a relationship between mutational burden, or the rate of somatic mutations, and response to immunotherapy. [SCLC] certainly has a high mutational load, which presumably translates to a higher neoantigen load,” he added.

Dr Liu goes on to mention the IMPower133 study, where patients were given atezolizumab plus carboplatin/etoposide or a placebo with carboplatin/etoposide. Patients, all of whom had not received prior systemic treatment for ES-SCLC, received carboplatin/etoposide with atezolizumab or a placebo for 4 21 day cycles, then continued receiving one or the other for a maintenance period.

The difference in median progression-free survival (PFS) was not significant, with the atezolizumab mPFS being 5.2 months (95% CI, 4.4-5.6) and 4.3 months (95% CI, 4.2-4.5) for the placebo group. However, the overall survival (OS) after 12 months was 51.7% (median, 12.3 months; 95% CI, 10.8-15.9) and 38.2% (median, 10.3 months; 95% CI, 9.3-11.3), respectively.

Quality of life also improved for the atezolizumab group, who noted meaningful improvement in symptoms sooner than the placebo group. The FDA approved atezolizumab combination therapy in 2019. 

In 2020, the FDA approved durvalumab and etoposide/platinum, following the results of the CASPIAN study, which compared the efficacy of durvalumab and etoposide/platinum with and without tremelimumab. Results showed higher efficacy and safety without the addition of tremelimumab.

The median OS of patients in the durvalumab plus chemotherapy group was 13.0 months (95% CI, 11.5-14.8), and 10.4 months in the durvalumab and tremelimumab combination group (95% CI, (9.6-12.0), while etoposide/platinum alone was 10.5 months (95% CI, 9.3-11.2).

Dr Liu noted that these studies provided the first major change to SCLC treatment in over 3 decades.

“These are welcomed advances, we have new standards of care in a highly lethal disease where we clearly need better outcomes, but there’s notable room for improvement and a lot of ongoing trials are showing promise,” he concluded.—Alexandra Graziano