We performed a clinical audit of the management of patients with mutations, 1 year after the introduction of tyrosine kinase inhibitor (-TKI) in first-line treatment. Compliance was defined by tumor molecular profiling for stage IIIB and IV non-small-cell lung cancer and first-line treatment as recommended by the French guidelines. Among the 169 -mutated patients, compliance was 76.4%. The most common noncompliance criterion was chemotherapy given in first-line treatment instead of -TKI. No dedicated multidisciplinary meeting and type of institutions were independent unfavorable predictors for compliance. Compliance to guidelines was significantly correlated with time-to-first subsequent treatment improvement (2.5 vs 9.1 months; p < 0.0001). Implementation of new standards of care is challenging. Our results reinforce the role of multidisciplinary meetings to provide a better access to innovating therapeutics.