Abstract
Oligoprogression in MET Exon 14 skipping (METex14)-mutated non-small cell lung cancer (NSCLC) is clinically challenging, particularly when local therapies are contraindicated. We report the first documented case of a 62-year-old man with oligoprogressive METex14-positive NSCLC who achieved a sustained metabolic response following the addition of docetaxel to ongoing tepotinib therapy after progression on tepotinib monotherapy. Due to prior thoracic irradiation, reirradiation and surgical interventions were deemed not feasible, prompting this systemic combination to maintain MET inhibition while targeting resistant tumor clones. This strategy resulted in a partial metabolic response at the primary lung lesion and a sustained complete metabolic response in an adrenal metastasis. The regimen was generally well tolerated; however, Grade 3 peripheral edema required dose reduction of tepotinib. This case supports the potential role of systemic therapy intensification in METex14-driven NSCLC, highlighting the therapeutic value of continued MET inhibition beyond disease progression, particularly when local treatment and advanced molecular monitoring such as ctDNA are unavailable. Trial Registration: ClinicalTrials.gov identifier: NCT05439993.