Outcomes of personalized therapy guided by Exacta encyclopedic tumor analysis for women with broadly refractory advanced breast cancer.

Abstract

e13124 Background: Following the failure of three lines of systemic treatments in breast cancers, Standard of Care guidelines typically recommend palliative care or participation in clinical trials for such patients. Breast cancer remains a global health threat, impacting lives worldwide. For refractory patients, the outlook is grim, with limited treatment options post multiple failures. Dismal outcomes underscore the urgency for innovative approaches, as traditional interventions often fall short. Methods: The Resilient trial was a Phase-II, single-arm, open-label clinical trial. Its primary objective was to assess the effectiveness of Exacta ETA-guided treatments across a spectrum of solid organ cancers in advanced refractory cancer patients. Exacta Encyclopedic Tumor Analysis (ETA) comprising the interrogation of gene alterations, gene expression, immunohistochemistry (IHC), and in vitro chemoresistance profiling (CRP) of viable tumor cells was performed on freshly obtained tumor tissue from 21 breast cancer patients with broadly refractory advanced breast cancers who had failed multiple lines of treatment. Six (29%) patients had metastasis to the brain, 11 (52%) patients had metastasis to the liver, 9 (43%) patients had metastasis to the lungs, and 15 (71%) patients had skeletal metastasis. The findings obtained through Exacta ETA were integrated to formulate patient-specific therapy recommendations. Personalized treatment plans were devised, and organ- and label-agnostic treatment regimens were administered to each patient. Patients were monitored to ascertain Overall Survival (OS). Results: Median overall survival (OS) was not reached at the time of analysis. By considering the OS values censored at the interim (most recent follow-up), the median OS in the entire cohort (n = 21) was 11.5 months (95% CI 4.5 to 16.9). The median OS was 11.4 months (95% CI 4.0 to 15.1) among patients with brain metastases, 14.5 months (95% CI 2.6 to 22.8) among patients with liver metastases, 11.9 months (95% CI 3.7 to 22.3) among patients with pulmonary metastases and 11.4 months (95% CI 3.7 to 22.3) among patients with skeletal metastases, respectively. No grade IV adverse events or treatment-related deaths were reported in the cohort. Conclusions: Exacta Encyclopedic Tumor Analysis (ETA) guided treatments provide a viable and meaningful treatment option for patients with advanced refractory breast cancers with metastatic deposits. The observed high OS in this heavily pretreated population underscores the value of multi-analyte guided of Exacta ETA as a valuable approach to managing these challenging clinical cases. Clinical trial information: CTRI/2018/02/011808.