Olaparib with or without bevacizumab versus bevacizumab plus a fluoropyrimidine as maintenance therapy in advanced colorectal cancer: The randomized phase 3 LYNK-003 study
Mené sur 309 patients atteints d'un cancer colorectal de stade métastatique ou non résécable (durée médiane de suivi : 7,6 mois), cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement d'entretien par olaparib avec ou sans bévacizumab et d'un traitement combinant bévacizumab et une fluoropyrimidine
Background: The randomized, open-label, phase III LYNK-003 study assessed the efficacy of first-line maintenance olaparib, alone or in combination with bevacizumab, versus bevacizumab plus a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer (mCRC). We present results of the prespecified interim futility analysis. Methods: Eligible participants were
≥
18 years of age with unresectable or mCRC that had not progressed after induction with first-line bevacizumab plus FOLFOX (5-fluorouracil plus oxaliplatin plus leucovorin) or CAPOX (capecitabine plus oxaliplatin). Participants were randomly assigned 1:1:1 to olaparib plus bevacizumab, olaparib alone, or bevacizumab plus a fluoropyrimidine (5-fluorouracil or capecitabine). The primary end point was progression-free survival (PFS) per RECIST v1.1 by central review. Results: Between August 2020 and May 2022, 309 participants were assigned to olaparib plus bevacizumab (n = 104), olaparib (n = 107), or bevacizumab plus fluoropyrimidine (n = 98). At interim analysis, with a median follow-up of 7.6 months (range 0.1–19.7 months), the median PFS was 3.7 months (95% CI 2.8–5.3) with olaparib plus bevacizumab (HR 1.52; 95% CI 1.02–2.27; P = 0.982) and 3.5 months (95% CI 2.0–3.7) with olaparib (HR 2.11; 95% CI 1.39–3.18; P = 0.999) versus 5.6 months (95% CI 3.8–5.9) with bevacizumab plus fluoropyrimidine. Treatment-related adverse events occurred in 64 (62%), 52 (50%), and 57 (59%) participants, respectively. There were no treatment-related deaths. Conclusion: The LYNK-003 study was stopped prematurely as criteria for futility were met. Maintenance olaparib with or without bevacizumab did not demonstrate clinical efficacy compared with bevacizumab plus a fluoropyrimidine.