NICE Recommends Dostarlimab Plus Chemo in MSI-High/dMMR Endometrial Cancer

The United Kingdom’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending the approval of the monoclonal antibody dostarlimab-gxly (Jemperli) in combination with chemotherapy for the treatment of adult patients with advanced or recurrent microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR) endometrial cancer.^1,2

Although the pivotal phase 3 RUBY trial (NCT03981796) demonstrated an efficacy benefit with dostarlimab plus chemotherapy in these patients, long-term data from this trial are not yet mature. Therefore, dostarlimab has been recommended for use in the Cancer Drugs Fund (CDF) and will be available in the National Health Service (NHS) to treat adult patients with advanced or recurrent endometrial cancer as further data are collected. Furthermore, dostarlimab plus chemotherapy represents the fourth treatment option that NICE has recommended for patients with endometrial cancer for either routine NHS commissioning or CDF use since the founding of NICE in 1999.¹

“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, stated in a news release. “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 CDF, enabling [patients] with this type of cancer to enjoy more precious time with their families and loved ones.”

The RUBY trial enrolled 494 patients with primary advanced (stage III or IV) or recurrent endometrial cancer, including 118 patients with dMMR/MSI-H disease.² Patients were randomly assigned 1:1 to receive intravenous (IV) dostarlimab at 500 mg or IV placebo plus carboplatin at an area under the curve of 5 mg/mL/min and paclitaxel at 175 mg/m² every 3 weeks for 6 cycles. Patients receiving the dostarlimab treatment were allowed to continue IV dostarlimab at 1000 mg every 6 weeks for up to 3 years, and patients receiving placebo could continue IV placebo every 6 weeks for up to 3 years.

Investigator-assessed progression-free survival (PFS) and overall survival (OS) served as the primary end points of the RUBY study. Key secondary end points included PFS by blinded independent central review, overall response rate, duration of response, disease control rate, patient-reported outcomes, and time to second progression.

In July 2023, the FDA approved dostarlimab plus chemotherapy for adult patients with primary advanced or recurrent dMMR/MSI-H endometrial cancer, based on findings from an interim analysis of part 1 of RUBY, in which the dostarlimab regimen elicited a 71% reduction in the risk of disease progression or death vs chemotherapy alone.³ In the overall population, the 24-month PFS rates were 36.1% (95% CI, 29.3%-42.9%) in the dostarlimab arm and 18.1% (95% CI, 13.0%-23.9%) in the placebo arm (HR, 0.64; 95% CI, 0.51-0.80; P < .001).⁴ In the dMMR/MSI-H population, the estimated 24-month PFS rates were 61.4% (95% CI, 46.3%-73.4%) and 15.7% (95% CI, 7.2%-27.0%) in the dostarlimab and placebo arms, respectively (HR, 0.28; 95% CI, 0.16-0.50; P < .001).

In the overall population, the 24-month OS rates were 71.3% (95% CI, 64.5%-77.1%) with dostarlimab vs 56.0% (95% CI, 48.9%-62.5%) with placebo (HR, 0.64; 95% CI, 0.46-0.87). In the dMMR/MSI-H population, the 24-month OS rates were 83.3% (95% CI, 66.8%-92.0%) and 58.7% (95% CI, 43.4%-71.2%) in the dostarlimab and placebo arms, respectively (HR, 0.30; 95% CI, 0.13-0.70).

Adverse effects (AEs) of grade 3 or higher occurred in 70.5% and 59.8% of patients in the dostarlimab and placebo arms, respectively. The most common AEs that occurred or worsened during dostarlimab treatment were nausea (53.9%), alopecia (53.5%), and fatigue (51.9%).

References

1. New treatment option available today for womb cancer. News release. NICE. March 5, 2024. Accessed March 5, 2024. https://www.nice.org.uk/news/article/new-treatment-option-available-today-for-womb-cancer
2. Single technology appraisal. Dostarlimab with platinum-based chemotherapy for treating advanced or recurrent endometrial cancer with high microsatellite instability of mismatch repair deficiency [ID3986]. Committee papers. NICE. 2024. Accessed March 5, 2024. https://www.nice.org.uk/guidance/gid-ta10850/documents/committee-papers
3. 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. GlaxoSmithKline. July 31, 2023. Accessed March 5, 2024. https://www.gsk.com/en-gb/media/press-releases/jemperli-plus-chemotherapy-approved-in-us-for-new-indication/
4. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. Published online March 27, 2023. doi:10.1056/NEJMoa2216334