Less Is More, But Me-Too Should Not Be the Strategy for Lung Cancer Treatment in 2026.

Although immune checkpoint inhibitors (ICIs) and targeted therapies (TTs) have transformed the treatment of non-small cell lung cancer (NSCLC) across disease stages, real-world access remains highly unequal worldwide. Persistent cost barriers, fragmented reimbursement frameworks, and heterogeneous regulatory pathways limit equitable availability. The rapid proliferation of me-too agents has been proposed to counter monopolies; yet, this expansion has not consistently improved affordability. Heterogeneous evidentiary requirements-along with differences in clinical end points, comparator selection, crossover policies, and treatment duration-fragment therapeutic markets and complicate assessment of incremental clinical benefit. Divergent regulatory decisions, particularly between the US Food and Drug Administration and European Medicines Agency, underscore how trial design and geographic representation influence drug availability, especially when approvals rely on single-country data sets. These challenges are amplified in perioperative treatment strategies and rare oncogene-defined subgroups, where feasibility constraints and limited clinical equipoise hinder large randomized trials. As a result, an increasingly crowded therapeutic landscape makes cross-trial comparisons difficult and allows disparities in patient access to persist despite multiple approved therapies. Dose selection has historically followed maximum tolerated dose principles, even when preclinical and pharmacologic data suggest activity plateaus at lower exposure of ICI and TT. Dose and schedule optimization-through reduced dosing, extended intervals, or other deintensified strategies-therefore represents a rational and ethically grounded approach with a meaningful clinical impact. Such strategies may preserve efficacy while improving tolerability, reducing treatment burden, and mitigating financial toxicity, particularly in resource-limited settings. Aligning regulatory frameworks with dose optimization could promote more scalable, equitable, and sustainable NSCLC innovation.