As reported in the Journal of Clinical Oncology by Tung et al, findings in expansion cohorts of the phase II Translational Breast Cancer Research Consortium (TBCRC) 048 study showed that olaparib was active in patients with metastatic breast cancer with germline PALB2 mutations (gPALB2m) and in those with somatic BRCA1/2 mutations (sBRCAm).
Study Details
In the U.S. multicenter trial cohorts, 54 patients with gPALB2m (n = 24) or sBRCAm (n = 30) received olaparib at 300 mg twice daily until disease progression or unacceptable toxicity. A total of 42 patients (78%) had HER2-negative disease and 7 (13%) had triple-negative disease. The primary endpoint was confirmed objective response rate.
Key Findings
Among the 24 patients with gPALB2m, objective responses (including 1 complete response) were observed in 18 patients (75%, 80% confidence interval [CI] = 60.2%–86.3%). Median duration of response was 7.0 months (90% CI = 5.6–10.4 months). The clinical benefit rate at 18 weeks was 83.3% (90% CI = 65.8%–94.1%). Median progression-free survival was 9.4 months (90% CI = 8.3–13.1 months).
Among the 30 patients with sBRCAm, objective responses (including 2 complete responses) were observed in 11 patients (36.7%, 80% CI = 24.7%–50.0%); an additional patient had an unconfirmed partial response. Median duration of response was 11.2 months (90% CI = 4.4 months to not reached). The clinical benefit rate at 18 weeks was 53.3% (90% CI = 37.0%–69.1%). Median progression-free survival was 5.5 months (90% CI = 2.8–8.3 months). Among patients with sBRCAm, no difference in mean mutant allele frequency was observed between responders and nonresponders (46% vs 39%, P = .7).
Grade 3 treatment-related adverse events occurred in 24% of patients, most commonly anemia (13%) and fatigue (7%); no grade 4 or 5 events were observed. Treatment-related adverse events led to discontinuation of treatment in one patient.
The investigators concluded: “Olaparib is active in [patients with metastatic breast cancer] with gPALB2m and sBRCAm, significantly expanding the population of [patients] with breast cancer likely to benefit from PARP inhibitors beyond gBRCA1/2m carriers.”
Nadine M. Tung, MD, of Harvard Medical School, Boston, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by AstraZeneca and the TBCRC, which is funded by the Breast Cancer Research Foundation and Susan G. Komen. For full disclosures of the study authors, visit ascopubs.org.
