Study of pembrolizumab regimen in endometrial cancer yields ‘encouraging new finding’
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Key takeaways:
- Researchers reported a 70% reduction in the risk for disease progression or death among women with mismatch repair-deficient disease.
- Women with mismatch repair-proficient disease had a 46% reduction in risk.
The addition of pembrolizumab to chemotherapy significantly extended PFS for women with advanced or recurrent endometrial cancer, according to study results presented at Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
Researchers observed the benefit regardless of mismatch repair status among women who received the combination as first-line treatment for stage III to stage IV disease, the findings showed.
“The efficacy curves separated early in treatment, with a preserved separation throughout the evaluation period,” Ramez N. Eskander, MD, gynecologic oncologist and assistant professor of obstetrics, gynecology and reproductive sciences at Moores Cancer Center at UC San Diego Health, said during a presentation.
Pembrolizumab also did not appear to increase the frequency of adverse events associated with the chemotherapy regimen, he added.
Background and methods
Paclitaxel plus carboplatin has been established as the standard first-line chemotherapy regimen for women with endometrial cancer, one of the few malignancies with increasing incidence and mortality. Eskander and colleagues sought to determine whether adding the anti-PD-1 antibody pembrolizumab (Keytruda, Merck) to this regimen would extend PFS among women with advanced or recurrent disease.
The prospective, randomized, international phase 3 NRG-GY018 trial included 816 women with measurable stage III/stage IVA or measurable/nonmeasurable stage IVB recurrent endometrial cancer. Researchers assigned the women in a 1:1 ratio to six cycles of 200 mg IV pembrolizumab or placebo every 3 weeks, followed by as many as 14 maintenance cycles of 400 mg pembrolizumab or placebo every 6 weeks, plus paclitaxel and carboplatin. Women who received prior adjuvant chemotherapy could participate if they had a treatment-free interval of at least 12 months.
The investigators stratified women into two cohorts based on central mismatch repair (MMR) immunohistochemistry. The deficient-MMR (dMMR) cohort included 225 women and the proficient-MMR (pMMR) cohort included 591 women.
PFS in the two cohorts served as the primary endpoint, with interim analyses triggered after 84 or more deaths or progression events in the dMMR cohort and 196 events in the pMMR cohort.
Median follow-up was 12 months in the dMMR cohort and 7.9 months in the pMMR cohort at the time of analysis Dec. 16.
Results and implications
The results, published simultaneously in The New England Journal of Medicine, showed median PFS in the dMMR cohort had not been reached among the pembrolizumab group vs. 7.6 months in the placebo group (HR = 0.3; 95% CI, 0.19-0.48). Researchers reported 12-month PFS rates for this cohort of 74% in the pembrolizumab group vs. 38% in the placebo group.
Median PFS in pMMR cohort was 13.1 months in the pembrolizumab group vs. 8.7 months in the placebo group (HR = 0.54; 95% CI, 0.41-0.71).
The PFS benefit with pembrolizumab and chemotherapy appeared consistent across all relevant subgroups, Eskander said.
Grade 3 or higher adverse events occurred at higher rates among patients who received pembrolizumab vs. placebo in the dMMR cohort (63.3% vs. 47.2%) and the pMMR cohort (55.1% vs. 45.3%); however, the groups had similar rates of grade 3 or grade 4 adverse events with incidence of 15% or higher. Researchers observed no new safety signals.
In a press release, Eskander described the PFS improvement in both mismatch-repair cohorts as “an encouraging new finding.”
“Future analysis will examine overall survival and quality-of-life outcomes,” he said in the press release.
References:
- Eskander RN, et al. N Engl J Med. 2023;doi:10.0156/NEJMoa2302312.
- Eskander R, et al. NRG GYO18/KEYNOTE-868: A phase III randomized, placebo-controlled study of pembrolizumab in addition to paclitaxel and carboplatin for measurable stage III or IVA, stage IVB or recurrent endometrial cancer (late-breaking abstract). Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, Florida.
- Society of Gynecologic Oncology. Two clinical trials reveal addition of immunotherapy to chemotherapy regimen increases progression-free survival in endometrial cancer patients (press release). Available at: www.newswise.com/articles/two-clinical-trials-reveal-addition-of-immunotherapy-to-chemotherapy-regimen-increases-progression-free-survival-in-endometrial-cancer-patients. Published March 27, 2023. Accessed March 27, 2023.
Collapse
Eskander RN, et al. NRG GYO18/KEYNOTE-868: A phase III randomized, placebo-controlled study of pembrolizumab in addition to paclitaxel and carboplatin for measurable stage III or IVA, stage IVB or recurrent endometrial cancer (late-breaking abstract). Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, Florida.
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