First-line durvalumab plus platinum-etoposide in extensive-stage small-cell lung cancer: CASPIAN Japan subgroup analysis

Abstract

Background In the phase 3 CASPIAN study (NCT03043872), first-line durvalumab plus etoposide and cisplatin or carboplatin (EP) significantly improved OS versus EP alone in patients with extensive-stage (ES)-SCLC (HR 0.73 [95% CI 0.59–0.91; p = 0.0047]). Here we report results for a preplanned subgroup analysis of patients recruited in Japan. Methods Treatment-naïve patients with ES-SCLC received either 4 cycles of durvalumab 1500 mg plus EP q3w followed by maintenance durvalumab 1500 mg q4w until disease progression or up to 6 cycles of EP q3w. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), safety, and tolerability. Results In the Japan subgroup, 18 patients were randomized to durvalumab plus EP and 16 patients to EP. At the interim analysis with a median follow-up of 12.5 months in the subgroup, OS numerically favored durvalumab plus EP versus EP (HR 0.77 [95% CI 0.26‒2.26]; median not reached vs 15.2 months). PFS was similar for durvalumab plus EP versus EP (HR 0.90 [95% CI 0.43‒1.89]). Confirmed ORR was 89% with durvalumab plus EP versus 69% with EP. Adverse events (AEs) of CTCAE grade 3 or 4 were reported in 78% versus 94% of patients in the durvalumab plus EP versus EP arms. There were no AEs leading to treatment discontinuation or death in the Japan subgroup. Conclusion First-line durvalumab plus EP was effective and well tolerated in Japanese patients with ES-SCLC. Despite the small size of the Japan subgroup, results were generally consistent with the global study population.

Durvalumab: A Review in Extensive-Stage SCLC

“…In a preplanned subgroup analysis of patients recruited in Japan ( n = 34; median follow-up 12.5 months), the addition of durvalumab to chemotherapy ( n = 18) compared with chemotherapy alone ( n = 16) was associated with an HR for OS of 0.77 [(95% CI 0.26–2.26); median OS not reached vs. 15.2 months] and an estimated OS rate at 12 months of 72.2% versus 60.2% [ 13 ]. In the durvalumab plus chemotherapy and chemotherapy alone groups, median PFS was 4.5 and 4.7 months (HR 0.90; 95% CI 0.43–1.89) and the confirmed ORR was 89% and 69% (odds ratio 3.64; 95% CI 0.65–28.75) [ 13 ].…”

“…Durvalumab in combination with etoposide and either carboplatin or cisplatin had a manageable tolerability profile in patients with ES-SCLC treated in the CASPIAN trial [ 11 , 12 ], including the subgroup of patients enrolled in Japan [ 13 ]. The safety profile of this regimen was consistent with the well-established safety profiles of the individual agents [ 11 , 12 ].…”

The efficacy and safety of immune checkpoint inhibitor in patients with relapsed small‐cell lung cancer: A systematic review and meta‐analysis

“…In recent years, many clinical trials about SCLC have been carried out, and breakthroughs have been made in the immunotherapy of SCLC 1,15,19,21,27 . Although some of the results are negative, 19 they still bring indications to the future treatment of relapsed SCLC.…”

“…In recent years, many clinical trials about SCLC have been carried out, and breakthroughs have been made in the immunotherapy of SCLC. 1,15,19,21,27 Although some of the results are negative, 19 they still bring indications to the future treatment of relapsed SCLC. In this study, we summarized the progress of immunotherapy for relapsed SCLC and performed a meta-analysis to assess the efficacy and safety of immunotherapy in patients with relapsed SCLC.…”

Clinical Relevance of Targeted Therapy and Immune-Checkpoint Inhibition in Lung Cancer

“…Additionally, between 2016 and 2019, atezolizumab and durvalumab were approved as anti PD-L1 mAbs for NSCLC [226][227][228]. Later, in 2020, durvalumab was also approved as a first-line treatment for ES-SCLC in combination with chemotherapy [229].…”