Immunotherapy in Advanced NSCLC Without Driver Mutations: Available Therapeutic Alternatives After Progression and Future Treatment Options

The treatment paradigm of non-small-cell lung cancer without oncogenic drivers has varied dramatically in recent years and is constantly evolving. Immune- checkpoint inhibitors have demonstrated unprecedented durable efficacy in a subset of these patients, so these drugs have become the standard of care in most cases. There are different ways to deliver these agents, such as monotherapy and combinations of immunotherapy or chemotherapy plus immunotherapy. Treatment selection is complicated by an absence of head-to-head comparisons in randomized trials because these agents have gained approval by demonstrating superiority to platinum-doublet chemotherapy alone. Unfortunately, most patients will progress and die from their disease despite advances. Furthermore, after progression on these agents, there is a lack of randomized controlled data to support further management, constituting an unmet need. This review discusses the therapeutic alternatives after progression, summarizes mechanisms of resistance and progression patterns, and describes the main approaches under clinical investigation in the field.