High Efficacy of Olaparib Confirmed in Metastatic Breast Cancer with Germline PALB2 and Somatic BRCA Mutations

In the germline PALB2 mutation cohort (n=24), the majority had ER-positive/HER2-negative disease (79%), with 8% HER2-positive and 13% triple-negative breast cancer (TNBC). Of these patients, the overall response rate (ORR) was 75%, with 18 confirmed responses, including one complete response. The clinical benefit rate at 18 weeks was 83%, with a median response duration of 7.1 months and median progression-free survival (PFS) of 9.6 months.

In the somatic BRCA mutation cohort (n=30), 50% had BRCA1 mutations and 50% had BRCA2 mutations. Most had ER-positive/HER2-negative disease (77%), 10% HER2-positive, and 13% TNBC. This group exhibited a 37% ORR, with 11 confirmed responses, including one complete response. The clinical benefit rate was 53%, with a median response duration of 12.4 months and a median PFS of 7.2 months. Notably, mutant allele frequency (MAF) did not predict response to olaparib in this cohort.

The study confirmed high response rates in patients with germline PALB2 mutations and underscored the importance of identifying predictors of response for patients with somatic BRCA mutations or germline PALB2 mutations. Next-generation sequencing (NGS) was highlighted as crucial for detecting mutations related to homologous recombination deficiency (HRD) or homologous recombination repair (HRR) genes in clinical practice.

Reference:

Nadine M. Tung et al., TBCRC 048 (olaparib expanded) expansion cohorts: Phase 2 study of olaparib monotherapy in patients (pts) with metastatic breast cancer (MBC) with germline (g) mutations in PALB2 or somatic (s) mutations in BRCA1 or BRCA2. JCO 42, 1021-1021(2024).

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