Poly (ADP-ribose) polymerase inhibitors (PARPi) have demonstrated impressive efficacy in BRCA-mutated gynaecological malignancies. Several lines of evidence now support that the DNA repair (DDR)-deficient populations that benefit from PARPi go far beyond BRCA-deficiency. Non-small cell lung cancer (NSCLC), the first cause of cancer death worldwide, displays frequent DDR defects, the most frequent being ERCC1. This defect leads to platinum and PARPi sensitivity. Beyond ERCC1, DDR defects leading to platinum sensitivity widely overlap with those underlying PARPi sensitivity. Maintenance PARPi could therefore benefit to patients (pts) with platinum-sensitive NSCLC. Olaparib (Lynparza®, Astra Zeneca), a potent and selective PARPi, was the first-in-class approved PARPi in BRCA-mutated ovarian cancer.
PIPSeN is a randomized double-blind phase II investigator-initiated study evaluating maintenance Olaparib versus placebo in pts with platinum-sensitive advanced NSCLC. Chemonaïve ECOG PS 0-1 pts with stage III-IV NSCLC with no EGFR mutation or ALK translocation are eligible. Treatment consists of an “induction phase” of 4-6 cycles platinum-based therapy (any doublet), followed by a “randomized phase” where pts presenting with partial or complete response are randomized between Olaparib maintenance (tablets; 300mg bd) and placebo until progression or unacceptable toxicity. Primary objective is to assess the efficacy of maintenance Olaparib as measured by Progression-Free Survival from randomisation (RECIST v1.1). Secondary objectives include comparison of overall survival, disease control rate and safety. Randomization is stratified according to age, histology and country. With an anticipated HR = 0.65 (bilateral α = 0.2; β = 0.2), approximately 500 enrolled pts will be required to randomize 144 pts and observe 97 events. Recruitment is ongoing since the 5th of Feb. 2016 across 21 centres in France and Spain; 95 (19) pts have been enrolled (randomised) to date. Translational studies looking notably for biomarkers of platinum and PARPi sensitivity (using WES, RNAseq, proteomics and ctDNA) are associated.
Clinical trial identification
EudraCT: 2014-005586-75 NCT02679963
Legal entity responsible for the study
Gustave Roussy Cancer Campus (sponsor), in collaboration with the Spanish Lung Cancer Group
D. Planchard: Consultancy fees for AstraZeneca, Boehringer Ingelheim, BMS, Lilly, MSD, Pfizer, Roche, Novartis, Chugai. M. Majem: Merck Sharp and Dhome, Boerhinger Ingelheim, Bristol-Myers Squibb, Roche, Novartis honoraria. F. Barlesi: AstraZeneca Honoraria. S. Viteri: Consulting/advisory (BI, Clovis, Idea Pharma, Novartis, Roche, Targovax), Research (AbbVie, ARIAD, Astex, AstraZeneca/MedImmune, BI, Clovis, CytRx, Daiichi Sankyo, GSK, Hanmi, Incyte, Merck, Novartis, Pfizer, Puma, Roche, Servier, Vaxon) B. Besse: Research grants from Astra Zeneca. J-C. Soria: Consultancy fees from AZ. All other authors have declared no conflicts of interest.