Improving outcomes in gyneco-oncology in late and last line setting: Real-world data from the molecular tumor board registry trial at the Comprehensive Cancer Center Freiburg (Germany).

Abstract

e17655 Background: Molecular tumor boards (MTBs) play a crucial role in personalized medicine in Germany, guiding the treatment of patients who have exhausted standard options. To generate evidence that can inform future therapeutic recommendations, data on molecular characteristics and treatment outcomes are needed. Methods: This study retrospectively analyzes the real-world data including the molecular landscape, MTB recommendations and their corresponding biomarkers as well as outcomes of patients with gynecologic malignancies (breast-, cervical-, endometrial-, ovarian-, vulvar cancer and uterine sarcoma who were discussed at the Molecular Tumor Board Freiburg (MTB-FR). Results: From 2019 to 2022, 262 cases of gynecologic malignancies (corresponding to 249 individual patients) were referred to the MTB-FR. N=229 cases (87.4%) received a recommendation for personalized diagnostics at the protein, DNA and/or transcriptomic level and were included in the analysis. This cohort was characterized as relatively young yet highly pretreated, with a significant unmet clinical need, as reflected by a mean age of 53.3 years and a mean of 3.1 prior lines of systemic treatment. Personalized diagnostics resulted in at least one treatment recommendation in n=170/229 (74.2%) cases, primarily off-label therapies. In 50.6% of cases, at least one potentially matching clinical trial could be identified. Molecularly informed therapy was implemented in n=63/170 cases (37.1%), while n=81/170 cases (47.6%) received none of the recommended treatments, predominantly due to deterioration in health status. In 15.3% of cases, the implementation of the recommended treatment was unclear due to loss to follow-up. The most prevalent implemented therapeutic agents were antibody-drug conjugates (25.7%) and immune checkpoint inhibitors (17.1%). 75.4% of implemented off-label treatments were supported by evidence from the same tumor entity (NCT level m1A-C). Clinical trials accounted for 12.9% of implemented treatments. In our retrospective analysis, patients who received an MTB-recommended therapy (n=61) exhibited a significantly longer median overall survival (OS) of 19 months compared to 6 months for those who did not receive an MTB-recommended therapy (n=59, log-rank p=0.0002). Conclusions: These results underscore the benefit of MTB referral in patients with gynecologic malignancies and highlight the importance of early intervention in this setting. Additional analysis and progression-free survival data are expected.