Immunotherapy is revolutionizing the natural history of several cancers. The demonstration also arrives for gynecological oncology and, specifically, for endometrial carcinoma, a neoplasm of the body of the uterus, with the results of the ‘Ruby’ study, presented at the Annual Meeting of Women’s Cancer, organized by the Society of American Gynecologic Oncology, scheduled in Tampa, Florida. “Clinical practice has waited for decades for significant progress in the standard of care for advanced or recurrent primary endometrial cancer,” says Mansoor Raza Mirza, principal investigator of the Ruby study, an oncologist at Copenhagen University Hospital, Denmark. given the difficult-to-treat histologies included in the study, they demonstrate support for a new standard of treatment with the addition of dostarlimab to current standard chemotherapy.”
The study – which involved adult patients with advanced or recurrent primary endometrial cancer – compared the use of dostarlimab, an immunotherapy, plus standard chemotherapy (carboplatin-paclitaxel) followed by dostarlimab versus chemotherapy plus placebo followed by placebo. The results show a 72% and 36% reduction in the risk of disease progression or death, respectively, in the population with a genetic condition known as microsatellite instability (dMMR/MSI-H) and in the overall patient population.
“We are excited”, the Ruby study “will change clinical practice”, comments Domenica Lorusso, associate professor of Obstetrics and Gynecology, head of the Clinical Research Programming Unit of the Irccs Foundation A. Gemelli University Hospital of Rome, in connection from Tampa, in a meeting with journalists organized by GSK, which developed immunotherapy. “Today – continues Lorusso – we have about 10,000 patients diagnosed every year and 3,000 who die of endometrial cancer which, for years, was considered to have a good prognosis This has led to a disinvestment in research and treatments. The consequence is that today it is the only oncological pathology with increasing mortality. In 80% of cases, the diagnosis occurs when it is confined inside the uterus, but in recurrence, in an advanced form, the median survival is 3 years. Until yesterday we only had chemotherapy with carboplatin and taxol”.
Cancer of the endometrium or uterine body represents almost all tumors affecting the uterus and is the fourth most frequent cancer in the female population after breast, colon and lung cancer. In Italy, 117,000 women are affected. Over 90% over 50 years of age. “The great bet of the Ruby study – explains Lorusso – was that immunotherapy with chemotherapy could enhance chemotherapy. The statistical design is complex with two objectives: to demonstrate progression-free survival and overall survival by first analyzing the patients who, for genetic reasons, having microsatellite instability (dMMR / MSI-H, in the study) they were more ready for therapy “and then extend it to the overall patient population. The results are extraordinary, they are things that we had never seen to date”.
Specifically, “for the first time in 20 years since we have been using taxol carboplatin – he clarifies – we have had an impressive improvement in the HR (Hazard ratio), i.e. the reduction in the risk of disease progression. In the population with microsatellite instability – the expert points out – the HZ has a value of 0.28 which, in fact, is a 72% reduction in the risk of progression: it is impressive. At 2 years, the risk of progression is reduced by 16% in women with chemotherapy alone, compared to 61% in those treated with immunotherapies. The curves (which describe the response to the 2 different treatments, ed) are separated immediately and remain separate for a long time. Even in the general population treated with immunotherapy, at 2 years, less than 20% have not yet relapsed and the HZ is 0.64, an important value. We also have overall survival data. The result is not complete, it was presented with 33% of maturity, but at 2 years 56% of patients with chemo alone are alive, against 71% of those who have undergone chemo and immunotherapy”.
The results of the study – shared in a virtual plenary session of the European Society of Medical Oncology (Esmo) and published simultaneously in the New England Journal of Medicine – are “positive for everyone, both in reducing the risk of disease progression and in overall survival – underlines Lorusso – Of course, the benefit is different, with an extraordinary 0.28 of HR”, i.e. of very low risk of progression, “in patients with microsatellite instability”, less impactful, but solid, the 0.76 of HZ in who does not have this genetic condition. But the study is positive: it means a 24% reduction in progression and a 27% reduction in the risk of death in a population in which there had been no news for 20 years. We don’t stop here – he concludes – It is the beginning” of a revolution that “changes the history of the disease for all patients, changes clinical practice”.
