The longer than anticipated median PFS observed in the PLD
group, when compared with the findings from the previous phase III
study by Gordon et al,14 likely impacted on the power of the study to
detect a difference in PFS between olaparib and PLD. However, the
efficacy of PLD in the current study is consistent with a recent retrospective
analysis that suggested a potential link between germline
BRCA1/2 status and greater clinical benefit achieved with PLD in this
disease setting.18 Moreover, a study by Graeser et al19 suggested a likely
correlation between functional homologous recombination deficiency
(defined using a RAD51 focus formation assay) and clinical
benefit from the use of neoadjuvant anthracycline-based chemotherapy
in sporadic breast cancer. Hence, it is conceivable that patients
with homologous recombination–deficient tumors, including those
with germline BRCA1/2 mutations, may derive more benefit from
anthracycline-based treatments than unselected patients, and this
clearly has implications for the design of further trials in this patient
population.