New (germ)line of therapy.

Headline: PARP inhibition is making a move to the front lines for patients with localized HER2(-) breast cancer and a germline BRCA mutation.

The Study: Remember, PARP inhibition is currently used to prolong progression-free survival for metastatic disease in this population, brought to us by another ASCO headliner four years ago—side note: happy 4th birthday to us! Results have been mixed in the neoadjuvant setting. Here we see how PARPi fairs in the maintenance setting. The double-blind phase 3 OlympiA trial (paper) randomized 1836 women with localized HER2(-) breast cancer to +/- maintenance olaparib x one year following surgery and standard (neo)adjuvant chemo. An important practical note is that maintenance olaparib did not start until at least 2 weeks after radiation. Eligible triple negative patients (82%) had either ≥cT2 or ≥cN1 or residual primary or nodal disease after neoadjuvant chemo. Hormone receptor-positive disease (the other 18%) required either 4+ involved nodes or extensive disease present after neoadjuvant chemo. Patients were unbilinded at the first interim analysis at 2.5 years given the already apparent improvement in the primary endpoint of invasive disease-free survival with maintenance olaparib (HR 0.58). What’s more, 3-year survival free from distant mets (88% vs 80%) and even overall survival (92% vs 88%) was significantly improved with olaparib.

TBL: Maintenance olaparib prolongs survival outcomes for select patients with high-risk localized HER2(-) breast cancer and a germline BRCA mutation. | Tutt, N Engl J Med 2021