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Although tyrosine kinase inhibitors (TKIs) are effective against non-small cell lung cancer (NSCLC) harboring sensitizing epidermal growth factor receptor(EGFR) gene mutations, acquired resistance is inevitable. Preclinical studies suggest combining EGFR TKI and monoclonal antibody therapies may have activity in EGFR-mutated NSCLC that has progressed on TKI therapy alone. Therefore, we prospectively evaluated afatinib plus necitumumab in patients with EGFR-mutated NSCLC.

FGFR3-TACC3fusions have been identified in patients with multiple cancer types, and tumors with these alterations are potentially sensitive to selective FGFR inhibitors. However, there are no FGFR inhibitors approved by the U.S. Food and Drug Administration for the treatment of patients with NSCLC with FGFRalterations. Here, we report a case of a patient with FGFR3-TACC3fusion squamous NSCLC who achieved a radiographic response and disease control for 11 months on initial treatment with erdafitinib and subsequently obtained an additional 8 months of disease control after erdafitinib retreatment after 5 months of intervening chemotherapy. Further investigation into FGFR inhibitor treatment specifically and targeted therapy retreatment for patients with NSCLC may increase our therapeutic options for these patients.

The application of KRAS G12C inhibitors in the setting of NSCLC represents a major milestone for a previously “undruggable” target. Here, we present the second reported case of de novo KRASG12C–mutant primary SCLC. Would our patient benefit from a KRAS G12C inhibitor?