Neoadjuvant PARP inhibitor scheduling in BRCA1 and BRCA2 related breast cancer: PARTNER, a randomized phase II/III trial

BRCA1, BRCA2 (germline status required for eligibility)

Randomized phase II/III trial: olaparib on D3–D14 intercalated between carboplatin and paclitaxel (4 neoadjuvant cycles) in gBRCA1/2 carriers. Assessment of pCR and 36-month survival.

The PARTNER trial (phase II/III) evaluates the addition of intercalated olaparib to neoadjuvant chemotherapy (carboplatin + paclitaxel) in germline BRCA1/2 breast cancer patients. The pathological complete response rate (pCR) is not significantly different between arms (64.1% vs 69.8%, p=0.59). However, event-free survival at 36 months is significantly improved in the olaparib arm (96.4% vs 80.1%, p=0.04), as is overall survival (100% vs 88.2%, p=0.04).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Striking and unexpected survival signal given the absence of pCR difference, raising questions about the schedule-dependent effect of olaparib. These results require confirmation before practice modification. Clinically, they reinforce the value of germline BRCA1/2 testing before any neoadjuvant treatment decision.

phase II/III RCT +2; unexpected survival signal (96% vs 80%) +2; impact on pre-treatment germline testing +2; Nat Commun +1