medwireNews: Heavily pretreated patients with metastatic breast cancer characterized by a high tumor mutational burden (TMB) are likely to derive “meaningful clinical benefit” from pembrolizumab monotherapy, say the TAPUR researchers.
“Our findings support and extend results of the KEYNOTE-158 trial […] that led to the recent FDA approval of pembrolizumab in patients with unresectable or metastatic solid tumors with [high] TMB who have no satisfactory alternative treatment options,” say Pam Mangat (American Society of Clinical Oncology, Alexandria, Virginia) and colleagues.
They explain that the TAPUR study was designed “to identify signals of activity for targeted anticancer drugs used outside of their FDA-approved indications,” adding that the FDA decision came after study initiation.
The team reports on 28 patients with advanced metastatic breast cancer and a high TMB (median 13 mutations/Mb, range 9–37 mutations/Mb) recruited from 14 US cancer centers between 2016 and 2018. Most (93%) patients had received three or more prior systemic treatments, 89% had HER2-negative tumors, 50% were hormone receptor-positive, and 46% had triple-negative breast cancer.
Treatment with pembrolizumab 2 mg/kg (n=8) or 200 mg (n=20) every 3 weeks, depending on the prescribing label at time of enrollment, achieved a disease control rate of 37%, defined as a complete or partial response at 8 weeks or later or stable disease for at least 16 weeks. The objective response rate was 21%.
Median progression-free survival was 10.6 weeks and median overall survival was 30.6 weeks. Neither endpoint appeared to be associated with TMB, note the researchers, but they emphasize that “the study was not powered to detect such an association.”
The study authors write in the Journal of Clinical Oncology that “[t]hese results demonstrate that pembrolizumab has activity similar to that reported for other solid tumors in patients with [metastatic breast cancer] with [high] TMB.”
Drug-related adverse events (AEs) of grade 3 or 4 occurred at a rate of 11%, as did drug-related serious AEs of any grade. An additional four grade 3 AEs and four grade 2–3 serious AEs were at least possibly related to pembrolizumab, report the authors. In total, six patients discontinued treatment due to an AE.
Mangat et al acknowledge the limitations of the study, including “the relatively small size of the cohort and heterogeneous composition of the study population.”
But despite including patients with various breast cancer subtypes with “fundamentally different disease courses,” the researchers say they “are encouraged that patients with each of these breast cancer subtypes experienced meaningful clinical benefit in this cohort.”
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