Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): Updated results from the phase III CASPIAN study.
Authors: Luis G. Paz-Ares, Mikhail Dvorkin, Yuanbin Chen, Niels Reinmuth, Katsuyuki Hotta, Dmytro Trukhin, Galina Statsenko, Maximilian Hochmair, Mustafa Özgüroğlu, Jun Ho Ji, Oleksandr Voitko, Artem Poltoratskiy, Francesco Verderame, Libor Havel, Igor Bondarenko, Jon Armstrong, Natalie Byrne, Haiyi Jiang, Jonathan Wade Goldman
Journal: Journal of Clinical Oncology (2020)

9002 Background: CASPIAN is an open-label, Phase 3 study of durvalumab (D) ± tremelimumab (T) + etoposide and either cisplatin or carboplatin (EP) for pts with 1L ES-SCLC. At the planned interim analysis (data cutoff Mar 11, 2019; 63% maturity), D + EP demonstrated a statistically significant improvement in OS compared with EP alone (HR 0.73 [95% CI 0.59–0.91]; p=0.0047). Here we present a planned updated analysis of OS for D + EP vs EP and the first results for D + T + EP vs EP. Methods: Treatment-naïve pts with ES-SCLC (WHO PS 0/1) were randomized 1:1:1 to D 1500 mg + EP q3w, D 1500 mg + T 75 mg + EP q3w, or EP q3w. In the IO arms, pts received 4 cycles of EP + D ± T, followed by maintenance D 1500 mg q4w until disease progression. Pts received one additional dose of T 75 mg post EP in the D + T + EP arm. In the EP arm, pts received up to 6 cycles of EP and optional PCI (investigator’s discretion). The two primary endpoints were OS for D + EP vs EP and for D + T + EP vs EP. Results: 268, 268 and 269 pts were randomized to D + EP, D + T + EP and EP, respectively; baseline characteristics were generally well balanced across arms. As of Jan 27, 2020, the median follow-up was 25.1 mo, 82% maturity. D + EP continued to demonstrate improvement in OS vs EP, with a HR of 0.75 (95% CI 0.62–0.91; nominal p=0.0032); median OS 12.9 vs 10.5 mo, respectively. 22.2% of pts were alive at 2 y with D + EP vs 14.4% of pts with EP. D + T + EP numerically improved OS vs EP, however this did not reach statistical significance per the prespecified statistical plan: HR 0.82 (95% CI 0.68–1.00; p=0.0451 [p≤0.0418 required for stat sig]); the median OS was 10.4 mo and 23.4% of pts were alive at 2 y. Secondary endpoints of PFS and ORR remained improved with D + EP vs EP and will be presented. Confirmed investigator-assessed ORR was similar for D + T + EP vs EP (58.4% vs 58.0%). Median PFS was similar for D + T + EP vs EP (4.9 mo vs 5.4 mo), but the 12-mo PFS rate was numerically higher (16.9% vs 5.3%); PFS HR 0.84 (95% CI 0.70–1.01). In the D + EP, D + T + EP and EP arms, respectively, incidences of all-cause AEs of Grade 3/4 were 62.3%, 70.3% and 62.8%; AEs leading to discontinuation 10.2%, 21.4% and 9.4%; and AEs leading to death 4.9%, 10.2% and 5.6%. Conclusions: The addition of durvalumab to EP continued to demonstrate improvement in OS compared with a robust control arm, further supporting this regimen as a new standard of care for 1L ES-SCLC offering the flexibility of platinum choice. No additional benefit was observed when T was combined with D + EP in this pt population. Safety findings in all arms remained consistent with the known safety profiles of all agents. Clinical trial information: NCT03043872.