Olaparib with or without bevacizumab in advanced colorectal cancer

The LYNK-003 study was stopped prematurely because maintenance olaparib with or without bevacizumab didn’t show any significant clinical benefit, as compared to bevacizumab plus a fluoropyrimidine, in advanced colorectal cancer. Results were recently published on European Journal of Cancer.

Authors involved patients with unresectable or metastatic colorectal cancer that had not progressed after induction with first-line bevacizumab plus 5-fluorouracil plus oxaliplatin plus leucovorin  or capecitabine plus oxaliplatin. Participants were randomly assigned to the PARP inhibitor olaparib plus bevacizumab, olaparib alone or bevacizumab plus a 5-fluorouracil or capecitabine; after a median follow-up of 7,6 months there were no new safety signals but the median progression-free survival was  3.7 months with olaparib plus bevacizumab and 3.5 months with olaparib  versus 5.6 months  with bevacizumab plus fluoropyrimidine. As authors explain, the outcomes of the study may have been limited by a preponderance of negative prognostic factors in the study population; however, «the LYNK-003 study was stopped prematurely at the prespecified progression-free survival futility analysis due to a lack of clinical efficacy of maintenance olaparib with or without bevacizumab compared with standard of care with bevacizumab plus a fluoropyrimidine», authors say. «These data illustrate the challenge associated with optimizing maintenance regimens while balancing toxicity in this difficult-to-treat population with mCRC. Patient selection remains an important factor in assessing PARP inhibitor efficacy and should be considered in future studies in the metastatic colorectal cancer population», authors conclude.