The clinical benefit of molecular re-assessments in management of progressive lung cancer.

Despite the enormous success of molecularly targeted therapy in advanced non-small cell lung cancer (NSCLC), long-term disease control remains challenging. Almost all patients on targeted therapy ultimately progress due to plethora of acquired resistance mechanisms. While acquired resistance mechanisms in BRAF-V600 mutant malignant melanomas treated with targeted therapy are well studied, little is known about resistance mechanisms in BRAF-V600 mutant lung cancer so far. Therefore, patients progressing on the standard BRAF and MEK inhibitor combination are uniformly switched to immune- and/or chemotherapy. We describe the case of a metastatic BRAF-V600E mutant pulmonary adenocarcinoma of the left lung with presumed progression of a single lung lesion at the right side during targeted therapy. Due to oligo-progression, resection was performed. Molecular re-assessment for analysis of acquired resistance mechanisms surprisingly revealed a genetically distinct second primary malignancy. Following curative resection of the right sided second primary NSCLC, primary tyrosine kinase inhibitor therapy was continued and to date the patient is still responding with a cumulative treatment duration of now 34 months. This case report illustrates that a thorough molecular re-assessment upon progression on targeted therapies may have a decisive influence on subsequent treatment decisions and should therefore be considered on a routine basis.