Inter- and intra-patient heterogeneity of response and progression to targeted therapy in metastatic melanoma.

MAPK inhibitors (MAPKi) are active in BRAF-mutant metastatic melanoma patients, but the extent of response and progression-free survival (PFS) is variable, and complete responses are rare. We sought to examine the patterns of response and progression in patients treated with targeted therapy.MAPKi-naïve patients treated with combined dabrafenib and trametinib had all metastases ≥5 mm (lymph nodes ≥15 mm in short axis) visible on computed tomography measured at baseline and throughout treatment.24 patients had 135 measured metastases (median 4.5/patient, median diameter 16 mm). Time to best response (median 5.5 mo, range 1.7-20.1 mo), and the degree of best response (median -70%, range +9 to -100%) varied amongst patients. 17% of patients achieved complete response (CR), whereas 53% of metastases underwent CR, including 42% ≥10 mm. Metastases that underwent CR were smaller than non-CR metastases (median 11 vs 20 mm, P