The study involved 263 patients in more than 100 centers based in Europe, North America, China and Israel.
Longer progression-free survival
The primary endpoint was an improvement in progression-free survival. That is the length of time patients live with the disease without it worsening and is a standard indicator to evaluate treatments in cancer studies.
“The prognosis of advanced endometrial cancer is very poor: patients typically relapse within 3 to 4 months of first-line chemotherapy and survive less than a year on average. The current standard of care is a ‘watch and wait’ approach, as no maintenance therapy exists,” says Dr. Vicky Makker, principal investigator in the US and medical oncologist at the Memorial Sloan Kettering Cancer Center.
Prof. Dr. Ignace Vergote, global principal investigator and gynecologist oncologist at University Hospitals Leuven in Belgium: “Our study showed that oral treatment with selinexor prolongs the time before patients relapse. The effect was especially large in the pre-specified, exploratory subgroup of patients with a working p53 gene (p53wt): their progression-free survival at the median was about 10 months longer. This is not a cure, but we are one step closer to offering patients a treatment option that can give them more time with their friends and family. The side effects were generally manageable with supportive care and dose modifications when needed. The global health status, physical functioning and symptoms were similar in both groups.”
Targeted treatment
Normally, the tumor suppressor gene p53 prevents the development of cancer. The gene is therefore also called ‘the guardian of the genome’. In cancer cells, p53 does not work sufficiently, partly because it is pulled out of the cells by transport proteins. The drug selinexor blocks those transport proteins, allowing p53 to perform its normal antitumor function.
Selinexor is already approved for hematological malignancies in Europe and the US.
The pharmaceutical company plans to initiate a new placebo-controlled, randomized study of selinexor in advanced or recurrent p53wt endometrial cancer to support a future supplemental new drug application (sNDA) with the FDA.
About endometrial cancer
Endometrial cancer is the most common cancer of the female reproductive organs and the fifth most common overall form of cancer in women. In 2020, there were approximately 130,000 new cases in Europe and 417,000 new cases worldwide. The majority of cases are diagnosed early and treated by surgically removing the tumor, but this is no longer an option for patients who have advanced or recurrent endometrial cancer.
About the study
The ENGOT-EN5/GOG-3055/SIENDO study was launched by the European Network for Gynaecological Oncological Trial (ENGOT) groups, with the Belgian and Luxembourg Gynaecological Oncology Group (BGOG) as lead group, and later conducted in collaboration with the US GOG Foundation and the pharmaceutical company Karyopharm.
The results have recently been presented at a virtual plenary session of the European Society of Medical Oncology (ESMO) meeting and will soon be submitted for publication in a scientific journal.
About ENGOT and BGOG (https://engot.esgo.org and www.bgog.eu)
The European Network of Gynaecological Oncology Trial groups (ENGOT) is a platform that guarantees that the European spirit and culture is incorporated into the medical progress in gynaecological oncology, and that all European patients and countries can participate in an active way in clinical research and progress. The ultimate goal is to bring the best treatment to gynecological cancer patients through the best science and enabling every patient in every European country to access a clinical trial. The Belgium and Luxembourg Gynaecological Oncology Group (BGOG) is one of the founding study groups of ENGOT.
About The GOG Foundation, Inc. (GOG) (www.gog.org)
The GOG Foundation, Inc. is a not-for-profit organization with the purpose of promoting excellence in the quality and integrity of clinical and translational scientific research in the field of gynecologic malignancies. The GOG Foundation is committed to maintaining the highest standards in clinical trials development, execution, analysis, and distribution of results. The GOG Foundation is the only clinical trialist group in the United States that focuses its research on patients with pelvic malignancies, such as cancer of the ovary (including surface peritoneal malignancies), uterus (including endometrium, soft tissue sarcoma, and gestational trophoblastic neoplasia), cervix, and vulva. The GOG Foundation is multi-disciplinary in its approach to clinical trials, and includes gynecologic oncologists, medical oncologists, pathologists, radiation oncologists, oncology nurses, biostatisticians (including those with expertise in bioinformatics), basic scientists, quality of life experts, data managers, and administrative personnel.
About GOG Partners
Supported by industry, GOG Partners has been structured to work directly with pharmaceutical organizations and operate clinical trials outside the National Cancer Institute (NCI) framework. The GOG Partners shares the same mission of the GOG Foundation dedicated to transforming the care in Gynecologic Oncology. By providing an alternative venue for patient accrual and site infrastructure support, GOG Partners has helped provide additional trials and opportunities for patients outside the national gynecologic clinical trials network.