Targeting K-Ras cancers

Abstract

phase I clinical trial of erlotinib and nivolumab in patients with EGFR mutated tumors has been completed (10). The regimen was feasible and well tolerated with promising antitumor activity. A randomized phase III trials of an EGFR-TKI versus an EGFR-TKI with an immune checkpoint inhibitor has been launched. Similar preclinical evidence supports the evaluations of ALK-TKIs plus an immune checkpoint inhibitor (8). Phase I testing has begun. Immunotherapy combinations. Optimizing the immune system to attack tumors will require exploiting its diverse components. Employing a dual immune approach with antiPD-1 plus an antiCTLA-4 agents has been successful in treating advanced melanoma. In lung cancer phase III trials of PD-1 and CTLA-4 inhibitors have been activated based on encouraging phase I data (12). Meanwhile, early phase trials evaluating immune checkpoint inhibitors with immune checkpoint agonists, cytokines, and vaccines are ongoing to determine the safest and most effective combinations. Overall we are optimistic that combination regimens that can harness the immune system together with tumor directed therapies will lead to improved clinical benefit. Continued pursuit of optimal combinations will however require increased insight into the complex interactions between the tumor, the immune response and pharmacological interventions.