Pembrolizumab shows promise in metastatic breast cancer with high tumor mutational burden
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Pembrolizumab demonstrated antitumor activity among women with heavily pretreated metastatic breast cancer characterized by high tumor mutational burden, according to phase 2 results from the TAPUR basket study.
The findings, published in Journal of Clinical Oncology, support the FDA approval last year of the anti-PD-1 antibody pembrolizumab (Keytruda, Merck) for patients with unresectable or metastatic solid tumors with high mutational burden who lack alternative treatment options, researchers noted.
“Immunotherapy does not work for every patient, but when it does work, it can have profound effects,” Ajjai S. Alva, MD, MBBS, oncologist and clinical associate professor of medical oncology, hematology and internal medicine at University of Michigan, said in a press release. “When it comes to a biomarker to tell us which patients will respond best to immunotherapy, we still have not found the perfect marker, the holy grail — but we have found a very good candidate biomarker in high tumor mutational burden.”
Researchers sought to identify signals of antitumor activity with pembrolizumab among patients with high tumor mutational burden.
The study included 28 women (median age, 63 years; 75% white) with advanced metastatic breast cancer with high tumor mutational burden, ranging from nine mutations/megabase to 37 mutations/megabase, enrolled between October 2016 and July 2018 across 14 clinical sites. Most women (64%) had an ECOG performance status of 1 and 36% had a performance status of 0.
Treatment consisted of pembrolizumab dosed at either 2 mg/kg or 200 mg infusions every 3 weeks. Disease control, defined as objective response or stable disease for at least 16 weeks, served as the primary endpoint.
Researchers used a Simon’s two-stage design, which required enrollment of 10 patients in a stage I cohort and, if at least two patients achieved disease control, an additional 18 additional patients in stage II. PFS, OS and safety served as secondary endpoints.
Four patients enrolled in stage I achieved either an objective response (n = 1) or stable disease for at least 16 weeks (n = 3), allowing enrollment to proceed to the second stage.
Results showed an overall disease control rate of 37% (95% CI, 21-50) and objective response rate of 21% (95% CI, 8-41). Median PFS was 10.6 weeks (95% CI, 7.7-21.1) and median OS was 30.6 weeks (95% CI, 18.3-103.3).
Researchers observed no association between degree of high tumor mutational burden and PFS or OS, although they noted the study was not powered for this analysis.
Drug-related grade 3 to grade 4 adverse events occurred among 11% of patients.
“Mutational burden has been shown to be helpful in identifying patients likely to benefit from pembrolizumab across multiple cancer types,” Alva said. “And our results in metastatic breast cancer are consistent [with] those reported since in other solid tumors.”
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