TY - JOUR
T1 - Olaparib maintenance versus placebo in platinum-sensitive non-small cell lung cancer
T2 - the Phase 2 randomized PIPSeN trial
AU - Postel-Vinay, Sophie
AU - Coves, Juan
AU - Texier, Matthieu
AU - Aldea, Mihaela
AU - Gazzah, Anas
AU - Dómine, Manuel
AU - Planchard, David
AU - De Las Peñas, Ramon
AU - Sala Gonzalez, Ma Angeles
AU - Viteri, Santiago
AU - Perez, Javier
AU - Ortega, Ana Laura
AU - Moran, Teresa
AU - Camps, Carlos
AU - Lopez-Martin, Ana
AU - Provencio, Mariano
AU - Soria, Jean Charles
AU - Besse, Benjamin
AU - Massuti, Bartomeu
AU - Rosell, Rafael
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Limited 2023.
PY - 2024/2/24
Y1 - 2024/2/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85179685796&partnerID=8YFLogxK
U2 - 10.1038/s41416-023-02514-5
DO - 10.1038/s41416-023-02514-5
M3 - Article
AN - SCOPUS:85179685796
SN - 0007-0920
VL - 130
SP - 417
EP - 424
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 3
ER -