On March 27, 2020, the US Food and Drug Administration approved durvalumab in combination with etoposide plus carboplatin or cisplatin for the first-line treatment of patients with small cell lung cancer with extensive disease (SCLCext).
The approval was based on CASPIAN, a multicenter, controlled and open study (NCT03043872), which randomly randomized patients to three treatment arms (in the proportion of 1: 1: 1): durvalumab plus platinum-etoposide (n = 268); durvalumab plus tremelimumab plus platinum-etoposide (n = 268); or platinum-etoposide only (n = 269).
The overall survival (OS) results in the comparison of the durvalumab plus platinum-etoposide (EP) versus EP groups were published in The Lancet in October 2019, based on a planned interim analysis. Progression-free survival (PFS) data assessed by the investigator and objective response rate (ORR) according to RECIST v1.1 were also released.
The association of durvalumab plus EP resulted in a statistically significant increase in OS, with a hazard ratio of 0.73 (95% CI 0.59-0.91; p = 0.0047); the median OS was 13.0 months (95% CI: 11.5-14.8) in the durvalumab arm plus EP compared to 10.3 months (95% CI: 9.3-11.2) in the arm chemotherapy.
Although the SLP was not tested for statistical significance at the time of the interim analysis due to the design of the study, the result indicated a hazard ratio of 0.78 (95% CI: 0.65-0.94), with a median SLP of 5.1 months (95% CI: 4.7-6.2) in the durvalumab arm plus EP compared to 5.4 months (95% CI: 4.8-6.2) in the chemotherapy isolated arm.
The ORR assessed by the investigator was 68% (95% CI: 62% -73%) in the durvalumab plus EP arm and 58% (95% CI: 52% -63%) in the chemotherapy arm. The most common adverse reactions (≥20%) in patients with SCLCext were nausea, fatigue / asthenia and alopecia.
Durvalumab should be administered before chemotherapy infusion on the same day. The recommended dose of durvalumab when administered with etoposide and carboplatin or cisplatin is 1500 mg EV every 3 weeks for 4 cycles; then, every 4 weeks on monotherapy as a maintenance scheme.
The results of the CASPIAN study are in agreement with the already published data from IMpower133 (atezolizumab plus EP), consolidating immunotherapy as the first line of treatment for small cell lung cancer in extensive disease. Therefore, this approval of durvalumab by the American FDA guarantees patients another alternative treatment in this scenario.
More details about the studies:
Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939.
Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018; 379(23):2220-2229.