In a small group of women with mismatch repair (MMR) deficiency endometrial uterine cancer, survival was increased by pembrolizumab, according to a presentation at the Society for Gynecologic Oncology 2016 Annual Meeting on Women’s Cancer.1
Pembrolizumab, an immunotherapy checkpoint inhibitor, is FDA-approved for the treatment of skin, kidney, and lung cancers. MMR deficiency has been predictive of benefit from pembrolizumab in colorectal cancer, and MMR deficiency is present in 20% to 30% of endometrial cancers. MMR-deficient tumors are characterized by thousands of mutated, newly formed antigens that are not yet recognized by the immune system.
As a result, these tumors could be sensitive to immune augmentation therapy with programmed death-1 (PD-1) blockade. Pembrolizumab blocks PD-1 from intercepting its ligands.
This ongoing, single-institution, phase II study examined early response rates and survival outcomes in 9 women with recurrent or persistent MMR-deficient endometrial uterine cancer treated with pembrolizumab. These women all received at least 1, but up to 4 (median 2), previous standard-of-care treatments.
The overall response rate is 56% (n = 5, 95% CI 21-85%). Of the 5 responders, 1 was a complete response and 4 were partial responses. The clinical benefit rate, a summation of complete response, partial response, and stable disease, was 88.9% (n = 8). Overall survival (OS) at 12 months was 89%, with median OS not yet reached. Median follow-up duration so far is 9.1 months (range, 7 to 18 months). No toxicities higher than grade 3 have been reported.
Two patients experienced disease progression, 1 with increased small-volume disease in the retroperitoneum and liver and a partial response in pulmonary nodules. This woman remained on pembrolizumab 6 months after disease progression and is asymptomatic.
The patient who experienced complete response had received 3 surgeries and 3 previous therapies. She has been without evidence of disease for 17 months.
“PD-1 blockade shows promising activity in MMR-deficient EC [endometrial uterine cancer]. A cooperative group study of PD-1 blockade in a larger cohort of women with both MMR-deficient and MMR-intact, recurrent, or persistent EC is planned,” wrote the researchers.
1. Fader AN, Diaz LA, Armstrong DK, et al. Preliminary results of a phase II study: PD-1 blockade in mismatch repair-deficient, recurrent or persistent endometrial cancer. Presentation at: 47th Annual Meeting of the Society of Gynecologic Oncology; March 19-22, 2016; San Diego, California. Late-breaking abstract 3.