Pembrolizumab shows early promise in repair-deficient endometrial cancer

PD-1 blockade with pembrolizumab may serve as a promising treatment strategy for women with recurrent or persistent mismatch repair-deficient endometrial cancer, according to preliminary phase 2 study results presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

These findings warrant further study in a larger cohort of women with recurrent or persistent endometrial cancer, according to the researchers.

Between 20% and 30% of endometrial cancers are mismatch repair-deficient. These tumors harbor mutant neoantigens that may respond to immune augmentation therapy with PD-1 blockade, which has shown efficacy in other cancer subtypes.

Amanda Nickles Fader, MD, associate professor of gynecology and obstetrics and director of the Kelly Gynecologic Oncology Service at Johns Hopkins School of Medicine, and colleagues are conducting an ongoing, single-site study to evaluate the clinical efficacy of pembrolizumab (Keytruda, Merck) — an immune checkpoint inhibitor approved by the FDA for melanoma, lung cancer and kidney cancer — in women with previously treated recurrent or persistent endometrial cancer with mismatch repair-deficiency.

The study includes nine patients with endometrial cancer who have failed prior standard of care therapy (median prior therapies, 2). The researchers assigned patients to IV pembrolizumab (10 mg/kg) every 2 weeks.

All patients completed at least one evaluation at the time of reporting, with a median follow-up of 9.1 months (range, 7-18). No toxicities higher than grade 3 have been reported.

Although response rates in this patient population typically range from 20% to 30%, the overall response rate to pembrolizumab at the time the analysis was 56% (95% CI, 21-86; n = 5).

One woman achieved a complete response and four achieved partial responses. Researchers noted the patient who achieved a complete response underwent three surgeries before entering the trial and had received three prior therapy lines. At the time of the analysis, she had been without evidence of disease for 17 months.

The disease control rate is 88.9% (n = 8).

Median OS has not been reached, but eighty-nine percent of women achieved 12-month OS.

Two patients experienced disease progression. One patient had an increase of small-volume disease in the liver and retroperitoneum, with a partial response in multiple pulmonary nodules. She remains on pembrolizumab 6 months after progression and is currently asymptomatic, according to researchers.

“A cooperative group study of the PD-L1 blockade in a larger cohort of women with both mismatch repair–deficient and mismatch repair–intact, recurrent or persistent endometrial cancer is planned,” Fader and colleagues wrote. – by Cameron Kelsall

Reference:

Fader AN, et al. LBA 3. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 19-22, 2016; San Diego.

Disclosure: HemOnc Today could not confirm the researchers’ relevant financial disclosures at the time of reporting.