Olaparib maintenance versus placebo in platinum-sensitive non-small cell lung cancer: the Phase 2 randomized PIPSeN trial

Sophie Postel-Vinay, Juan Coves, Matthieu Texier, Mihaela Aldea, Anas Gazzah, Manuel Dómine, David Planchard, Ramon De Las Peñas, Ma Angeles Sala Gonzalez, Santiago Viteri, Javier Perez, Ana Laura Ortega, Teresa Moran, Carlos Camps, Ana Lopez-Martin, Mariano Provencio, Jean Charles Soria, Benjamin Besse, Bartomeu Massuti, Rafael Rosell

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    Résumé

    Background: Platinum-sensitivity is a phenotypic biomarker of Poly (ADP-ribose) polymerase inhibitors (PARPi) sensitivity in histotypes where PARPi are approved. Approximately one-third of non-small cell lung cancers (NSCLC) are platinum-sensitive. The double-blind, randomized phase II PIPSeN (NCT02679963) study evaluated olaparib, a PARPi, as maintenance therapy for patients with platinum-sensitive advanced NSCLC. Methods: Chemonaïve patients with ECOG performance status of 0–1, platinum-sensitive, EGFR- and ALK-wild-type, stage IIIB-IV NSCLC were randomized (R) to receive either olaparib (O) maintenance or a placebo (P). The primary objective was progression-free survival (PFS) from R. Secondary objectives included overall survival (OS) and safety. With an anticipated hazard ratio of 0.65, 144 patients were required to be randomized, and approximately 500 patients enrolled. Results: The trial was prematurely terminated because anti-PD(L)1 therapy was approved during the trial recruitment. A total of 182 patients were enrolled, with 60 patients randomized: 33 and 27 in the O and P arms, respectively. Patient and tumor characteristics were well-balanced between arms, except for alcohol intake (33% vs 11% in the O and P arms, respectively, p = 0.043). The median PFS was 2.9 and 2.0 months in the O and P arms, respectively (logrank p = 0.99). The median OS was 9.4 and 9.5 months in the O and P arms, respectively (p = 0.28). Grade ≥3 toxicities occurred in 15 and 8 patients in O and P arms, with no new safety concerns. Conclusion: PIPSeN was terminated early after enrollment of only 50% of the pre-planned population, thus being statistically underpowered. Olaparib maintenance did neither improve median PFS nor OS in this patient population.

    langue originaleAnglais
    Pages (de - à)417-424
    Nombre de pages8
    journalBritish Journal of Cancer
    Volume130
    Numéro de publication3
    Les DOIs
    étatPublié - 24 févr. 2024

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