Advanced endometrial cancer: a new treatment improves survival rates
Results from two important studies involving women with advanced endometrial cancer – the fourth most common cancer in women – have been presented at the European Cancer Congress currently taking place in Madrid
Key points
It is the fourth most commonly diagnosed cancer in women in Italia, with around 8,650 new cases in 2024. But now a new antibody-drug conjugate (ADC), sacituzumab tirumecan (sac-TMT), could change the standard of care for endometrial cancer. At the European Society for Medical Oncology (ESMO) congress, which has just concluded in Madrid, data from the phase 3 TroFuse-005 trial were presented during the Presidential Symposium and published simultaneously in The Lancet. A therapeutic breakthrough which, as well as having a ‘Italian connection’ due to the involvement of Italian researchers, guarantees an additional seven months of median survival for women with advanced endometrial cancer that has continued to progress despite chemotherapy and immunotherapy, as well as the possibility, for some patients with metastatic disease, of keeping the disease under control for a long time without resorting to chemotherapy
Results on the efficacy of the treatment
The study evaluated sac-Tmt, an experimental ADC targeting Trop2, in patients with advanced or recurrent endometrial cancer who had previously been treated with platinum-based chemotherapy and anti-PD-1/L1 immunotherapy. The study involved 776 women across 242 centres in 31 countries and demonstrated significant improvements in overall survival and progression-free survival compared with chemotherapy using doxorubicin or paclitaxel. Sac-Tmt reduced the risk of death by 32 per cent, bringing the median overall survival to 19 months compared with 12 months with chemotherapy. It also reduced the risk of disease progression or death by 41 per cent, with a median progression-free survival of 7.2 months compared with 3.9 months. The response rate almost doubled, rising from 17 per cent to 35 per cent. “Sac-Tmt is the first anti-Trop2 ADC to demonstrate an improvement in overall survival in advanced or recurrent endometrial cancer in this setting compared with chemotherapy in a global phase 3 trial. Furthermore, TroFuse-005 showed a higher response rate and longer duration of response among patients treated with Sac-Tmt compared with chemotherapy”, says Domenica Lorusso, global lead investigator for TroFuse-005, lead investigator for Engot, director of the Gynaecological Oncology Programme at IRCCS Humanitas San Pio X and full professor at Humanitas University. “The incidence and mortality rates of endometrial cancer are rising worldwide, and the results of TroFuse-005 have the potential to change the way we treat patients who have previously received platinum-based chemotherapy and anti-PD-1/L1 immunotherapy”, emphasises the specialist.
The chemotherapy-free approach for some patients
At ESMO, also as part of the Presidential Symposium, the results of the Phase 3 Keynote-C93/GOG-3064/Engot-EN15 trial, published in *The Lancet*, were also presented. The study evaluated pembrolizumab as monotherapy in patients with advanced or recurrent endometrial cancer with mismatch repair deficiency (dMMR). At a 36-month follow-up, the median progression-free survival was 38 months with pembrolizumab compared with 8 months with chemotherapy, representing a 43 per cent reduction in the risk of progression or death. At 36 months, overall survival was 70 per cent with pembrolizumab compared with 62 per cent with chemotherapy. “Around 25 per cent of patients have a deficiency in the DNA damage repair system known as mismatch repair. Immune checkpoint inhibitors have significantly improved the prognosis for patients with advanced or recurrent endometrial cancer, particularly in the presence of this biological characteristic. Today, the standard of care consists of immunotherapy combined with chemotherapy, followed by maintenance immunotherapy. However, not all patients are suitable candidates for chemotherapy”, explains Sandro Pignata, the European principal investigator of the study and Director of Medical Oncology in the Department of Urogynaecology at the IRCCS Fondazione Pascale in Naples. “These results highlight the potential of a chemotherapy-free approach for some patients with advanced or recurrent dMMR endometrial cancer. It should also be emphasised that quality of life was found to be better with this approach. “Today,” he comments, “marks a significant success for Italian research, with two studies coordinated internationally by researchers from the Mito group.”
