ESMO 2024: Immunotherapy and Novel Antibody-Drug Conjugate Show Promise in Gynecologic Cancers
Key Insights
Pembrolizumab plus chemoradiotherapy significantly improved overall survival in high-risk locally advanced cervical cancer (search), establishing a new standard of care.
In high-risk endometrial cancer, pembrolizumab added to chemotherapy after surgery showed clinically meaningful improvements in disease-free survival specifically in dMMR tumors.
TORL-1-23, a novel antibody-drug conjugate targeting claudin 6 (search), demonstrated promising antitumor activity and tolerability in heavily pretreated ovarian (search) and endometrial cancers (search).
Studies presented at the European Society for Medical Oncology (ESMO) Congress 2024 highlight the potential of immunotherapy and a novel antibody-drug conjugate in treating early-stage gynecologic cancers. Researchers reported clinically meaningful benefits from adding immunotherapy to standard treatments for cervical and endometrial cancers (search), and promising antitumor activity with a novel antibody-drug conjugate in heavily pretreated patients with ovarian (search) and endometrial cancers.
Immunotherapy Improves Survival in Cervical Cancer
A phase III randomized, double-blind study revealed that pembrolizumab combined with concurrent chemoradiotherapy significantly improved overall survival in patients with high-risk locally advanced cervical cancer (search). The 3-year overall survival rate was 82.6% in the pembrolizumab group compared to 74.8% in the placebo group (P = .0040), with all patients receiving chemoradiotherapy.
Isabelle Ray-Coquard, MD, PhD, President of GINECO, stated, "The benefit in terms of improved overall survival should change our practice as soon as possible," noting that immunotherapy plus chemoradiotherapy represents a new standard of care for these patients. She emphasized the need to identify subgroups of patients who particularly benefit from immunotherapy and to determine optimal combination treatments.
Pembrolizumab Shows Promise in Endometrial Cancer Subgroup
Another phase III randomized study in women with newly diagnosed high-risk endometrial cancer found that adding pembrolizumab to chemotherapy after surgery did not improve disease-free survival in the overall study population. However, a subgroup analysis indicated that patients with deficient mismatch-repair (dMMR) tumors experienced clinically meaningful improvements in disease-free survival with immunotherapy.
Elene Mariamidze, MD, a medical oncologist and President of the Georgian School of Oncology, commented, "Although this trial is not positive in the study population as a whole, it gives us important information indicating that patients with endometrial dMMR tumors are more sensitive and reactive to immunotherapy." She suggested that these results will inform future research on immunotherapy in early-stage endometrial cancer.
Novel Antibody-Drug Conjugate Shows Antitumor Activity
A first-in-human phase I study of TORL-1-23, an antibody-drug conjugate targeting the protein claudin 6 (search), demonstrated good tolerability and antitumor activity in heavily pretreated patients with ovarian (search) and endometrial cancers (search) that expressed the protein. Claudin 6 is often aberrantly expressed in various cancers, including ovarian and endometrial cancers. The study reported "promising preliminary antitumor activity."
Dr. Ray-Coquard noted the significance of these findings, stating, "First, it paves the way for a new target for antibody-drug conjugates in gynecologic cancers, where we currently have very few validated ones. Second, the findings suggest potential efficacy in ovarian (search) cancer, a disease for which we currently have very few treatment options." She highlighted that claudin 6 (search) is of particular interest because its expression is very low in healthy cells, potentially reducing the risk of toxicity. The next steps involve confirming the response and duration of response, assessing the effect on progression-free survival in a larger cohort of ovarian cancer patients, and evaluating safety and efficacy in a phase III randomized clinical trial.
Future Directions in Gynecologic Cancer Treatment
Looking ahead, Dr. Mariamidze anticipates that combination therapies, potentially involving immunotherapy with chemotherapy or radiotherapy and targeted agents, will shape the future of gynecologic cancer treatment. She also emphasized the significant potential for developing personalized medicines, such as neoantigen vaccines and personalized immunotherapy based on tumor type and molecular characteristics.
Dr. Ray-Coquard concluded, "The studies presented at ESMO 2024 mark important progress in gynecologic cancer research, suggesting that several new treatment options may soon be available, which is very good for our patients... The development of new therapies such as immune therapy will offer the chance to cure more [patients with] early-stage gynecologic cancer and potentially with new [antibody-drug conjugates] to prolong overall survival."