The POSEIDON Trial: Will Secondary End Points Change Our Clinical Practice?

Mené sur 1 013 patients atteints d'un cancer du poumon non à petites cellules de stade métastatique, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité de l'ajout du durvalumab, avec ou sans trémélimumab, à une chimiothérapie de première ligne

Résumé en anglais

Over the past decade, the bleak therapeutic landscape for treatment-naive patients with advanced non–small-cell lung cancer (NSCLC) without targetable genomic alterations has been reinvigorated by the approval of immune checkpoint inhibitors (ICIs) according to different strategies: either with programmed cell death (ligand) protein 1 (PD-(L)1) inhibition monotherapy for selected patients or combined with platinum-based chemotherapy (CT) with or without CTLA-4 inhibition. Furthermore, dual-immunotherapy strategy (anti–PD-1 and anti-CTLA4) without CT has also been approved as a potential treatment approach in PD-L1 ≥ 1% tumors.1 However, not all the phase III clinical trials testing a dual-immunotherapy strategy reported a clear benefit in overall survival (OS) from the beginning compared with CT.2,3 Indeed, in several trials, the ICI strategy (PD-[L]1 with or without CTLA4 inhibition) underperformed compared with the CT alone during the first weeks of treatment, suggesting that a proportion of patients progress rapidly and die without obtaining any meaningful benefit from the ICI strategy. The addition of CT has been proposed as a potential strategy to overcome this scenario. Although it is still unknown whether the effect of CT combined with ICI is additive4 or synergistic,5 CT-ICI combinations have become the standard of care in the first-line setting regardless of histological subtype and PD-L1 expression.1 However, the real benefit of adding dual immunotherapy instead of monotherapy ICI to CT remains unknown. Indeed, questions about selection of the right patient population for dual ICI, the optimal number of CT cycles when combined with ICI, as well as the optimal duration of the ICI strategy need to be answered to balance the potential clinical benefit of prolonged treatment with the downside of a risk of increased toxicity.