Small cell lung cancer (SCLC) is a devastating diagnosis, and new therapeutic options are desperately needed in this setting. Previously, first-line treatment of extensive-stage SCLC was limited to combination chemotherapy, which is associated with modest overall survival (OS), but inroads have been made with the application of immune checkpoint inhibitor antibodies to this setting. Immunotherapy with nivolumab (anti-programmed cell death protein 1 [PD-1]) and ipilimumab (anti-cytotoxic T-lymphocyte antigen 4 [CTLA-4]) has been shown effective in patients relapsing on chemotherapy, and nivolumab received accelerated approval from the US Food and Drug Administration (FDA) last year for metastatic SCLC after platinum-based chemotherapy and at least 1 other line of therapy. Earlier this year, the anti–PD-1 ligand 1 (PD-L1) agent atezolizumab was approved by the FDA for use in combination with carboplatin and etoposide for the first-line treatment of extensive-stage SCLC, on the basis of a 2-month prolongation of median OS and a statistically significant increase in progression-free survival. The ongoing randomized phase III CASPIAN trial is evaluating the anti–PD-L1 durvalumab ± the CTLA-4 inhibitor tremelimumab in combination with etoposide and platinum-based chemotherapy (not restricted to carboplatin) compared with this chemotherapy alone as first-line therapy for extensive-stage SCLC. A recent interim analysis showed that the trial met its primary endpoint, with durvalumab and chemotherapy resulting in a statistically significant and clinically meaningful improvement in OS over chemotherapy alone. The safety profile was consistent with the established profiles of the agents. Full data from this study will be presented at a forthcoming meeting.
High Altitude: While therapeutic innovations have reshaped the treatment landscape in the past decade in non-small cell lung cancer (NSCLC), it has been challenging to find therapies that can make a difference in the disease course for SCLC. Extensive-stage SCLC has remained difficult to treat and is associated with poor long-term outcomes. The approval of atezolizumab and nivolumab and positive data with other immune checkpoint inhibitors provide an important proof of concept that the benefits of immunotherapy that were demonstrated in NSCLC can extend to patients with SCLC, in whom there remains a large unmet need. While full data from CASPIAN are not yet available, this announcement provides further evidence that inroads can be made for SCLC treatment, and encourages further exploration of immunotherapy in SCLC.
Ground Level: In SCLC, atezolizumab is currently approved for first-line use in combination with carboplatin and etoposide, and nivolumab can be used in third-line or later settings. Immune checkpoint inhibition has now been FDA approved in SCLC for approximately 1 year, and the latest data further support the utility of this class of therapy in SCLC. Although the recent positive OS benefit reported from CASPIAN does not guarantee that durvalumab will be added to the approved therapeutic repertoire for SCLC, it does demonstrate that active research in this area is steadily making inroads, providing further hope for improved outcomes in the future.
