Rapid Readouts: 3-Year Overall Survival Update From the Phase 3 CASPIAN Study
Afshin Dowlati, MD, discusses data from the following presentation: “Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): 3-year overall survival update from the Phase 3 CASPIAN study.” (Paz-Ares, ESMO 2021, LBA61)
- Background
- In CASPIAN, the phase 3 study of etoposide + cisplatin or carboplatin (platinum-etoposide, EP) ± durvalumab (D) ± tremelimumab (T) as first-line treatment of ES-SCLC, durvalumab + platinum-etoposide demonstrated a statistically significant improvement in overall survival (OS) vs platinum-etoposide alone (data cutoff: 11 Mar 2019; HR 0.73 [95% CI 0.59–0.91; P = .0047]).
- In a subsequent analysis after a median follow-up of 25.1 months (data cutoff: 27 Jan 2020), OS benefit with durvalumab + platinum-etoposide vs platinum-etoposide was sustained (HR 0.75 [95% CI 0.62–0.91; nominal P = .0032]), and durvalumab + tremelimumab + platinum-etoposide numerically improved OS vs platinum-etoposide (HR 0.82 [95% CI 0.68–1.00; P = .0451]), but did not reach statistical significance (P ≤ .0418).
- The updated OS after a median follow-up of >3 years, the longest reported to date for a phase 3 trial of platinum-etoposide + PD(L)1 in this disease setting, was reported at the European Society for Medical Oncology Congress 2021.
- Methods
- Patients with treatment-naïve ES-SCLC were randomized 1:1:1 to durvalumab 1500 mg + platinum-etoposide every 3 weeks, durvalumab 1500 mg + tremelimumab 75 mg + platinum-etoposide every 3 weeks, or platinum-etoposide every 3 weeks.
- Patients in the immuno-oncology arms received 4 cycles of platinum-etoposide + durvalumab ± tremelimumab, followed by maintenance durvalumab 1500 mg every 4 weeks.
- Patients in the platinum-etoposide arm received up to 6 cycles of platinum-etoposide .
- The 2 primary end points were OS for durvalumab + platinum-etoposide vs platinum-etoposide and for durvalumab + tremelimumab + platinum-etoposide vs platinum-etoposide .
- Serious adverse events (SAEs) were assessed during long-term follow-up.
- Results
- 268, 268, and 269 patients were randomized to durvalumab + platinum-etoposide, durvalumab + tremelimumab + platinum-etoposide and platinum-etoposide, respectively.
- At a data cutoff (DCO) of 27 Mar 2021, median follow-up was 39.4 months, 86% maturity.
- Durvalumab + platinum-etoposide, durvalumab continued to demonstrate improved OS vs platinum-etoposide: HR 0.71 (95% CI 0.60–0.86; nominal P = .0003).
- Median OS was 12.9 vs 10.5 months; 22.9% vs 13.9% of patients were alive at 24 months; and 17.6% vs 5.8% of patients were alive at 36 months with durvalumab + platinum-etoposide vs platinum-etoposide, respectively.
- Durvalumab + tremelimumab + platinum-etoposide continued to numerically improve OS vs platinum-etoposide: HR 0.81 (95% CI 0.67–0.97; nominal P = .02); median OS was 10.4 months, and 15.3% of patients were alive at 36 months.
- 46 patients remained on treatment with durvalumab at DCO (27 in the durvalumab + platinum-etoposide arm and 19 in the durvalumab + tremelimumab + platinum-etoposide arm).
- In durvalumab + platinum-etoposide, durvalumab + tremelimumab + platinum-etoposide and platinum-etoposide arms, respectively, incidences of SAEs (all causes) were 32.5%, 47.4%, and 36.5%; and adverse events leading to death (all causes) were 5.3%, 10.9%, and 6.0%.
- Conclusions
- Durvalumab + platinum-etoposide demonstrated sustained OS benefit over platinum-etoposide with a well-tolerated safety profile after >3 years of median follow-up, consistent with previous analyses.
- 3 times more patients were estimated to be alive at 3 years when treated with durvalumab + platinum-etoposide vs platinum-etoposide alone, further establishing durvalumab + platinum-etoposide as standard of care for first-line treatment of ES-SCLC.
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