Encyclopedic tumor analysis based personalised combination regimens improves patient outcomes in advanced and refractory solid cancers
Background: mTOR signaling pathway and angiogenic factors are commonly activated in solid tumors and present viable therapeutic targets. However, the use of mTOR inhibitors or angiogenic inhibitors as mono-therapies in clinical practice is impacted by certain limitations. On one hand, mTOR inhibitor mono-therapies have been demonstrated to have only a modest benefit with poor survival outcomes, while on the other hand, the indications for angiogenesis inhibitor (AGI) mono-therapy usage are restricted to only a select few cancers. The present study aimed to determine whether personalised patient-specific regimens that combine standard chemotherapeutic agents with either an mTOR inhibitor or an angiogenesis inhibitor (AGI) based on multi-analyte tumor interrogation yields significant treatment response and survival benefits in advanced or refractory solid organ cancers.
Methods: We evaluated treatment outcomes in a total of 109 patients diagnosed with advanced and/or refractory solid organ cancers. All patients received chemotherapeutic agents along with either an mTOR inhibitor (mTOR+ cohort, n=49) or an angiogenesis inhibitor (AGI+ cohort, n=60), as guided by ETA. Patients were followed-up with imaging studies to determine Objective Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS).
Results: Overall, among the 109 patients evaluated, complete response (CR) was observed in 1 (1%) patient, partial response (PR) was observed in 55 (50%) patients, stable disease (SD) was observed in 46 (43%) and progressive disease (PD) was observed in 7 (6%) patients. For the mTOR+ cohort, the ORR was 57.1%, DCR was 91.8%, median PFS was 4.9 months and median OS was 9.4 months. For the AGI+ cohort, the ORR was 46.7%, DCR was 95.0%, median PFS was 5.0 months and median OS was 8.9 months. Notably, 3 patients who had failed to respond to a prior first line mTOR inhibitor monotherapy, showed partial response when treated with ETA guided combination therapy with mTOR inhibitors. ETA guided therapies were generally well tolerated, with no Grade IV treatment related adverse events (AEs) or any treatment related deaths reported in either of the cohorts.
Conclusion: This study demonstrates the clinical efficacy of regimens that combine standard chemotherapeutic agents with mTOR inhibitors or AGI therapies in yielding clinically meaningful response rates and survival benefits, while also underlining the clinical utility of multi-analyte tumor profiling to support clinicians in designing personalised treatment strategies for patients with advanced or refractory cancers.