BRAF V600E stage IV lung adenocarcinoma with complete radiologic remission on dabrafenib-trametinib

What happened, in summary

This 85-year-old woman presented in December 2022 with worsening dry cough, shortness of breath, and severe limitation of daily activities. Her ECOG performance status was 2, and she required oxygen at 6 liters per minute during the day, at night, and with activity. CT staging showed a right lower-lobe lung lesion, hilar and mediastinal lymphadenopathy, and a left adrenal metastasis, consistent with Stage IV non-small cell lung cancer. Biopsy through endobronchial ultrasound-guided sampling confirmed NSCLC. Genomic profiling identified a BRAF V600E mutation, along with a TP53 missense variant, CHEK2 copy-number loss, MAPK3 frameshift variant, and an RNF43 variant in a microsatellite-stable tumor. PD-L1 TPS was high at 95%, and tumor mutational burden was 6.3 mut/Mb. In February 2023, she started dabrafenib 300 mg total daily dose plus trametinib 2 mg daily. She quickly reported clinical benefit, with gradual resolution of cough and dyspnea and discontinuation of oxygen therapy. After 1 month, CT showed marked reduction in the lung cancer and hilar/mediastinal lymph nodes, with central changes in the left adrenal metastasis. Fever and hyperpyrexia required repeated temporary treatment interruptions, and dabrafenib was reduced to 200 mg daily from June 2023. By November 2023, the right adrenal lesion was no longer visible, the lung lesion was reduced to residual scarring, and the left adrenal lesion was stable. As of February 2024, she was autonomous, ECOG 0, off oxygen, and had no radiologic evidence of active cancer. These imaging findings converted an initially symptomatic, oxygen-dependent course into radiologic remission on targeted therapy.