Durvalumab ± tremelimumab + platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): outcomes by PD-L1 expression and tissue tumor mutational burden
Mené sur des patients atteints d'un cancer du poumon à petites cellules de stade étendu, cet essai évalue l'efficacité, du point de vue de la survie globale, de l'ajout du durvalumab, avec ou sans trémélimumab, à une chimiothérapie de première ligne à base d'étoposide et de sels de platine, en fonction de l'expression tumorale de PD-L1 et de la charge mutationnelle du tissu tumoral
Résumé en anglais
Purpose: In the CASPIAN trial, first-line durvalumab plus platinum-etoposide (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small-cell lung cancer (ES-SCLC). We report exploratory analyses of CASPIAN outcomes by programmed cell death ligand-1 (PD-L1) expression and tissue tumor mutational burden (tTMB).
Experimental Design: Patients were randomized (1:1:1) to durvalumab (1500 mg) plus EP, durvalumab plus tremelimumab (75 mg) plus EP, or EP alone. Treatment effects in PD-L1 and tTMB subgroups were estimated using an unstratified Cox proportional hazards model.
Results: The PD-L1 and tTMB biomarker-evaluable populations (BEPs) comprised 54.4% (438/805) and 35.2% (283/805) of the intention-to-treat (ITT) population, respectively. PD-L1 prevalence was low: 5.7%, 25.8%, and 28.3% had PD-L1 expression on ≥1% tumor cells (TCs), ≥1% immune cells (ICs), and ≥1% TCs or ICs, respectively. OS benefit with durvalumab plus EP versus EP was similar across PD-L1 subgroups, with hazard ratios (HRs) all falling within the 95% CI for the PD-L1 BEP (0.47‒0.79). OS benefit with durvalumab plus tremelimumab plus EP versus EP was greater in PD-L1 ≥1% versus <1% subgroups, although CIs overlapped. There was no evidence of an interaction between tTMB and treatment effect on OS (durvalumab plus EP versus EP, p=0.916; durvalumab plus tremelimumab plus EP versus EP, p=0.672).
Conclusions: OS benefit with first-line durvalumab plus EP in patients with ES-SCLC was observed regardless of PD-L1 or tTMB status. PD-L1 expression may prove to be a useful biomarker for combined treatment with PD-(L)1 and CTLA-4 inhibition, although this requires confirmation with an independent dataset.
