Dostarlimab/Chemo Improves OS Vs Chemo in Advanced Endometrial Cancer

The FDA approved dostarlimab plus chemotherapy as a treatment for those with primary advanced or recurrent dMMR or MSI-H endometrial cancer in July 2023.

Dostarlimab (Jemperli) plus carboplatin and cisplatin followed by dostarlimab maintenance significantly improved overall survival (OS) compared with placebo plus chemotherapy among patients with primary advanced or recurrent endometrial cancer, according to a press release on updated findings from part 1 of the phase 3 RUBY/ENGOT-EN6/GOG3031/NSGO trial (NCT03981796).¹

The OS benefit with dostarlimab plus chemotherapy in the overall population met the primary end point of the RUBY trial. Investigators also reported a clinically meaningful OS benefit with the dostarlimab-based regimen among patients with mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) disease, and those with mismatch repair proficient or microsatellite stable (MSS) disease. According to previously published data, the experimental regimen, with respect to progression-free survival (PFS), reduced the risk of progression or death by 36% in the overall population (HR, 0.64; 95% CI, 0.51-0.80) and 72% in the dMMR/MSI-H subgroup (HR, 0.28; 95% CI, 0.16-0.50).²

Nausea, alopecia, fatigue, peripheral neuropathy, anemia, and arthralgia were the most common treatment-related adverse effects (TRAEs) observed in the RUBY trial. Investigators reported that the safety profile of dostarlimab in combination with carboplatin and cisplatin was comparable with prior reports of each individual agent.

Developers plan to have full results from the RUBY trial published in a medical journal and share their findings at a future scientific meeting.

“With today’s headline results from part 1 of the phase 3 RUBY trial, dostarlimab plus chemotherapy has become the only immunotherapy combination to show a survival benefit in this broader patient population in this treatment setting,” Hesham Abdullah, senior vice president and global head of Oncology Research & Development at GSK, said in the press release.¹ “We look forward to sharing detailed results of this analysis with regulatory authorities and the larger scientific community.”

In the RUBY trial, patients were randomly assigned 1:1 to receive 500 mg of dostarlimab or matched placebo plus 175 mg/m² of paclitaxel and carboplatin at area under the curve of 5 mg/mL per minute every 3 weeks for 6 cycles. Additionally, patients received maintenance dostarlimab at 1000 mg or placebo every 6 weeks for up to 3 years.

The trial’s other primary end point was investigator-assessed PFS. Secondary end points included objective response rate, duration of response, disease control rate, quality of life, and safety.

Patients 18 years and older with histologically or cytologically confirmed endometrial cancer with recurrent or advanced disease that is stage III or IV were able to enroll on the trial. Additional eligibility criteria included having adequate organ function and an ECOG performance status of 0 or 1.

The FDA approved dostarlimab plus chemotherapy as a treatment for those with primary advanced or recurrent dMMR or MSI-H endometrial cancer in July 2023.³ Additionally, the European Medicine Agency’s Committee for Medicinal Products for Human Use gave a positive opinion on approving the dostarlimab-based regimen in the same patient population in October 2023.⁴ The approval and positive opinion were both supported by data from the RUBY trial.

References

1. Phase III RUBY trial of Jemperli (dostarlimab) plus chemotherapy meets endpoint of overall survival in patients with primary advanced or recurrent endometrial cancer. News release. GSK. October 30, 2023. Accessed October 30, 2023. https://shorturl.at/NSW24
2. 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
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. GSK. July 31, 2023. Accessed October 30, 2023. https://shorturl.at/izGL9
4. GSK receives positive CHMP opinion recommending approval of JEMPERLI (dostarlimab) plus chemotherapy as a new frontline treatment for dMMR/MSI-H Primary advanced or recurrent endometrial cancer. News release. GSK. October 16, 2023. Accessed October 31, 2023. https://bit.ly/3QxXUb6