The European Commission has approved dostarlimab in combination with chemotherapy (carboplatin and paclitaxel) for first-line treatment of adult patients with primary advanced or recurrent endometrial cancer who are candidates for systemic therapy. This approval broadens the previous indication for dostarlimab plus chemotherapy in the European Union (EU) to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumours, which represent approximately 75% of patients diagnosed with endometrial cancer and who have limited treatment options.
Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “For the first time, all patients with primary advanced or recurrent endometrial cancer in the EU have an approved immuno-oncology-based treatment that has shown a statistically significant and clinically meaningful overall survival benefit. We’re proud dostarlimab continues to redefine the treatment landscape for patients.”
The incorporation of dostarlimab as an essential part of the treatment for patients affected by endometrial cancer with MMR pathway deficiency (dMMR/MSI-H) not only changed the therapeutic approach for these patients but also significantly improved their prognosis. Now, by extending the indication of this drug, all women with advanced endometrial cancer, whether newly diagnosed or recurrent, will have the opportunity to benefit from immunotherapy, allowing patients diagnosed with this disease to receive this treatment as part of first-line therapy. Improving the efficacy of first-line treatment for endometrial cancer was a major unmet need for our patients, and now, at last, we are beginning to address it. It is great news that, for the first time, we have access to a treatment that has demonstrated a benefit in Overall Survival for all patients with advanced EC, whether newly diagnosed or recurrent, who are candidates for systemic therapy,” adds Dr. Ana Oaknin, Head of the Gynecologic Tumors Unit at the Vall d’Hebron Institute of Oncology (VHIO) and Head of the Onco-Gynecology Department at the Medical Oncology Service of Vall d’Hebron University Hospital, as well as the principal investigator of the phase 1 GARNET clinical trial, which led to the first approval of dostarlimab in 2021.
The European Commission’s approval to expand the use of dostarlimab plus chemotherapy is based on results from Part 1 of the RUBY phase III trial. RUBY Part 1 is the only clinical trial in this setting to show a clinically meaningful and statistically significant overall survival) benefit in the full population of patients with primary advanced or recurrent endometrial cancer, demonstrating a 31% reduction in risk of death compared to chemotherapy alone.
At the 2.5-year landmark, the chance of being alive was 61% for patients in the dostarlimab plus chemotherapy group (245 patients) compared to 49% in the chemotherapy group (249 patients). In addition, a 16.4-month improvement in median OS was observed with dostarlimab plus chemotherapy versus chemotherapy alone (44.6 months vs. 28.2 months, respectively). The median duration of follow-up was more than three years.1 The safety and tolerability analysis from RUBY Part 1 showed a safety profile for dostarlimab plus carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse reactions (≥ 10%) in patients receiving dostarlimab plus chemotherapy were rash, rash maculopapular, hypothyroidism, pyrexia, alanine aminotransferase increased, aspartate aminotransferase increased and dry skin.
OS data were presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer on 16 March 2024, and were published in Annals of Oncology on 9 June 2024. The label for dostarlimab plus chemotherapy in the US was expanded to all adult patients with primary advanced or recurrent endometrial cancer in August 2024.
About endometrial cancer
Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynaecologic cancer in developed countries,2 with an estimated 1.6 million people living with active disease at any stage and 417,000 new cases reported each year worldwide.3 Incidence rates are expected to rise by approximately 40% between 2020 and 2040.4 In Europe, approximately 121,000 people are estimated to be diagnosed with primary advanced or recurrent endometrial cancer each year.5 Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.6 Among patients with primary advanced or recurrent endometrial cancer, approximately 75% have MMRp/MSS tumours.7
