NICE Recommends Dostarlimab/Chemo for MSI-H/dMMR Endometrial Cancer

Previously, the FDA approved dostarlimab plus chemotherapy for patients with advanced or recurrent dMMR/MSI-H endometrial cancer in July 2023.

The National Institute for Health and Care Excellence (NICE) has recommended the use of dostarlimab-gxly (Jemperli) in combination with platinum-containing chemotherapy as a treatment for patients with advanced or recurrent endometrial cancer that is microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR), according to final draft guidance published by the organization.¹

The NICE guidelines highlighted that this adjustment to the recommendations should not affect patients who started treatment before the guidance was published. Additionally, patients who are receiving treatment outside of the recommendation can continue without change to the funding and may stop if their clinician deems it appropriate.

The recommendation is backed by findings from the phase 3 RUBY trial (NCT03981796). According to data published in The New England Journal of Medicine, dostarlimab plus carboplatin and paclitaxel reduced the risk of disease progression or death by 72% compared with placebo plus chemotherapy among patients with dMMR/MSI-H tumors (HR, 0.28; 95% CI, 0.16-0.50; P <.001).² The estimated 24-month progression-free survival (PFS) rate was 61.4% (95% CI, 46.3%-73.4%) vs 15.7% (95% CI, 7.2%-27.0%) in each respective arm.

The most common adverse effects (AEs) observed in the dostarlimab and placebo arms, respectively, included alopecia (53.5% vs 50.0%) and fatigue (51.9% vs 54.5%). Investigators highlighted 5 deaths due to AEs in the dostarlimab arm.

“Advanced or recurrent womb cancer has a devastating effect on quality of life and there are limited treatment options available,” Helen Knight, director of medicines evaluation at NICE, said in a press release on the recommendation.³ “We are focused on delivering what matters most and getting care to those who need it fast, so I am delighted this treatment option will be made quickly available through the Cancer Drugs Fund [CDF], enabling [patients] with this type of cancer to enjoy more precious time with their families and loved ones.”

The FDA approved dostarlimab plus chemotherapy for patients with advanced or recurrent dMMR/MSI-H endometrial cancer in July 2023.⁴ Supporting data for the approval came from the RUBY trial.

“As a clinician, I celebrate the practice-changing potential of adding [dostarlimab] to chemotherapy for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer who have had limited treatment options. Based on the results from the RUBY clinical trial, I look forward to the addition of [dostarlimab] to chemotherapy becoming a new standard of care for patients,” principal investigator Matthew Powell, MD, chief of the Division of Gynecologic Oncology at Washington University School of Medicine, said in a press release at the time of the FDA approval.⁴

References

1. Dostarlimab with platinum-based chemotherapy for treating advanced or recurrent endometrial cancer with high microsatellite instability or mismatch repair deficiency. National Institute for Health and Care Excellence. March 5, 2024. Accessed March 5, 2024. https://tinyurl.com/ata6hm7n
2. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388(23):2145-2158. doi:10.1056/NEJMoa2216334
3. New treatment option available today for womb cancer. News release. National Institute for Health and Care Excellence. March 5, 2024. Accessed March 5, 2024. https://tinyurl.com/2k2zzvxr
4. Jemperli (dostarlimab) plus chemotherapy approved in the US as the first new frontline treatment option in decades for dMMR/MSI-H primary advanced or recurrent endometrial cancer. News release. GSK. July 31, 2023. Accessed March 5, 2024. https://shorturl.at/izGL9