Dostarlimab study ‘will change the lives of our patients’ with endometrial cancer
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Key takeaways:
- The addition of the anti-PD-1 antibody to chemotherapy led to a doubling of PFS at 24 months (36.1% vs. 18.1%).
- Researchers observed an even greater PFS benefit among women with dMMR-MSI-H tumors.
Dostarlimab plus carboplatin significantly increased PFS among women with primary advanced or recurrent endometrial cancer, according to study results presented at Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
The findings, simultaneously published in The New England Journal of Medicine, showed a substantial benefit with the dostarlimab (Jemperli, GSK) regimen among women with mismatch repair-deficient (dMMR), microsatellite instability-high (MSI-H) tumors.
Background and methods
Treatment of advanced-stage endometrial cancer has not changed since the adoption of carboplatin and paclitaxel almost 15 years ago, according to Mansoor Raza Mirza, MD, chief oncologist at Rigshospitalet in Denmark.
“Patients respond well to these therapies, but only for a short while. Overall survival is less than 3 years for these patients, so there is a real unmet need,” Mirza told Healio. “In 2014, the Cancer Genome Atlas data really started us thinking about how we are going to proceed, how we are going to classify these tumors and how we are going to divide patients into subgroups. At that time, it was also clear that immunotherapy in this disease usually works well and that was the initial reason why we decided to do this trial.”
The phase 3, global, double-blind, randomized, placebo-controlled ENGOT-ENG-NSGO/GOG-3031/RUBY trial included 494 women with primary advanced stage 3 or stage 4 or first recurrent endometrial cancer. Overall, 118 (23.9%) of women had dMMR/MSI-H tumors.
“The strong part of this trial is that we decided to allow patients who had received adjuvant chemotherapy for high-risk, early-stage disease and had relapsed after 6 months of therapy,” Mirza said.
Researchers randomly assigned women 1:1 to either dostarlimab, an anti-PD-1 antibody, dosed at 500 mg or placebo plus carboplatin (AUC-time curve, 5 mg/mL/minute) and paclitaxel (175 mg/m2 body-surface area), every 3 weeks for six cycles, followed by 1,000 mg dostarlimab or placebo every 6 weeks for up to 3 years.
Investigator-assessed PFS according to RECIST version 1.1, OS and safety served as primary endpoints.
Findings
Results showed 2-year PFS rates of 36.1% (95% CI, 29.3-42.9) with the dostarlimab regimen compared with 18.1% (95% CI, 13-23.9) with placebo (HR = 0.64; 95% CI, 0.51-0.8).
Researchers observed an even greater 2-year PFS benefit with dostarlimab among women with dMMR/MSI-H tumors (61.4% vs. 15.7%; HR = 0.28; 95% CI, 0.16-0.5).
In addition, 2-year OS rates were 71.3% (95% CI, 64.5-77.1) with dostarlimab vs. 56% (95% CI, 48.9-62.5) with placebo in the overall population (HR = 0.64; 95% CI, 0.46-0.87) and 83.3% vs. 58.7% in the dMMR/MSI-H population (HR = 0.3; 95% CI, 0.12-0.69).
The dostarlimab group had a higher objective response rate (77.6% vs. 69%) and longer duration of response than the placebo group.
Common adverse events included nausea in 53.9% of those assigned the dostarlimab regimen vs. 45.9% assigned placebo, alopecia in 53.5% vs. 50% and fatigue in 51.9% vs. 54.5%. Of note, the dostarlimab group had higher rates of grade 3 or greater (70.5% vs. 59.8%) and serious (37.8% vs. 27.6%) treatment-emergent adverse events.
“The results are amazing,” Mirza said. “At the 2-year follow-up, the number of patients with dMMR-MSI-H tumors who were relapse-free increased from 15% to 61%, which is unprecedented. The curves did not decrease after 1 year, but instead flattened, which allows me to believe that some of these patients are cured and will never experience relapse. We observed the same for the overall study population, with very strong PFS outcomes in both the dMMR-MSI-H tumor population and in the overall study population. It is no question that we will also see a strong benefit in OS, as well.”
Implications
“This study will change the lives of our patients,” Mirza told Healio. “Chemotherapy plus dostarlimab, given together and as monotherapy, is now a new standard of care for both the dMMR-MSI-H tumor population and the overall endometrial cancer population. I hope that we will soon get approval for this regimen and be able to treat our patients with it.”
References:
- ENGOT-EN6-NSGO/GOG-3031/RUBY trial results: The new standard of care in advanced/recurrent endometrial cancer (press release). Available at: ENGOT-EN6-NSGO/GOG-3031/RUBY trial results: | EurekAlert!. Published March 27, 2023. Accessed March 27, 2023.
- Mirza MR, et al. Dostarlimab in combination with chemotherapy for the treatment of primary advanced or recurrent endometrial cancer: a placebo-controlled randomized phase 3 trial. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, Florida.
- Mirza MR, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2216334.
For more information:
Mansoor Raza Mirza, MD, can be reached at mansoor.raza.mirza@regionh.dk.
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Mirza MR, et al. Final overall survival and long-term safety in the ENGOT-OV16/NOVA phase III trial of niraparib in patients with recurrent ovarian cancer. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, Florida.
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