Multi-analyte interrogation based treatment of advanced refractory cancers.

Abstract

e15624 Background: Treatment of advanced refractory cancers face challenges in non-availability of systemic therapy regimens with evidenced benefit. Post failure of two to three lines of systemic treatments, patients with such cancers are usually considered for palliation or clinical trials. Prior attempts at label-agnostic treatment regimens (precision medicine) in such populations were largely based on a single-indication-single-drug paradigm which had limited application. We hypothesized that advanced refractory malignancies have latent vulnerabilities which can be identified by an integrational multi-analyte interrogation of the tumor, and can be targeted using patient-specific combination regimens to yield clinical benefit. Methods: Fresh tumor tissue and blood samples were obtained from 158 patients with solid organ cancers where the disease had progressed following failure of at least two lines of standard of care systemic treatment options. These samples were used for Encyclopedic Tumor Analysis (ETA) which interrogated gene mutations, gene overexpression, pathway dysregulation, immunohistochemistry as well as in vitro chemosensitivity profiling of viable tumor cells. Integration of datasets from the multi-analyte ETA was used to generate patient-specific therapy recommendations. Patients who received ETA-guided treatments were followed up and response to treatment was retrospectively evaluated from radiological scans. Results: All patients received ETA-guided individualized treatments which were combinations of cytotoxic, targeted and endocrine agents. No two patients received the same treatment regimen. Complete or Partial Response (CR or PR) was observed in 76 patients yielding an Objective Response Rate (ORR) of 48.1%. 67 patients showed Stable Disease (SD), thus yielding a Disease Control Rate (DCR) of 90.5%. Median Progression Free Survival (PFS) was 117 days (Range 27 – 379 days). There were no Grade IV therapy related Adverse Events or therapy related deaths. Conclusions: Viable efficacious combination treatment options can be made available for patients with advanced refractory malignancies via ETA, despite perceived non-availability or non-viability of standard of care treatment options.