Sustained benefit of adjuvant olaparib in women with germline BRCA1- and BRCA2-associated high-risk HER2-negative early breast cancer: Updated results from the OlympiA phase III trial.

Pathogenic germline BRCA1 or BRCA2 variant targeted by pharmacological inhibition of poly-(ADP-ribose) polymerase (olaparib).

The randomised phase III OlympiA trial (NCT02032823) compared one year of adjuvant olaparib, an oral PARP inhibitor, with placebo in 1,836 patients carrying a pathogenic or likely pathogenic germline BRCA1 or BRCA2 variant and high-risk HER2-negative early breast cancer. This report covers the third pre-specified interim analysis at a median follow-up of 6.1 years, with descriptive analyses of the primary endpoint invasive disease-free survival (IDFS) and the secondary endpoints distant disease-free survival (DDFS) and overall survival (OS). Olaparib benefit was maintained for IDFS (HR 0.65; 95% CI 0.53-0.78), DDFS (HR 0.65; 95% CI 0.53-0.81) and OS (HR 0.72; 95% CI 0.56-0.93). Six-year OS was 87.5% with olaparib versus 83.2% with placebo, a difference of 4.4% (95% CI 0.9-6.7), with consistent benefit across all key subgroups including high-risk hormone receptor-positive disease. Fewer new BRCA-associated breast and ovarian or fallopian tube cancers occurred with olaparib, with no increase in adverse events of special interest (6.3% versus 9.3%), including myelodysplastic syndrome and acute myeloid leukaemia (0.4% versus 0.7%).

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

Sustained overall survival benefit at 6.1 years confirms that germline BRCA1/BRCA2 status is now a treatment decision and not merely family information: the turnaround time of the test, between diagnosis and the end of (neo)adjuvant chemotherapy, becomes the real practical bottleneck, which argues for early ordering by the oncologist with genetics consultation downstream. The methodological caveats are that this third interim analysis is descriptive and that the confidence interval around the 6-year survival difference is wide (0.9-6.7%), leaving room for a real absolute gain well below the headline 4.4%. The absence of excess myelodysplastic syndrome or acute myeloid leukaemia is reassuring but needs longer follow-up, since this risk is a late one in patients who are otherwise young and long-term survivors.

Analysis by Dr Thibaut Benquey