The predictive value of FDG PET/CT for determining progression-free survival in advanced stage III-IV BRAF-mutated melanoma patients treated with targeted therapy: what can be learned from progression?

Hiel, B. van der; Aalbersberg, E.A.; Eertwegh, A.J.M. van den; Veen, L.J.D.V. de van der; Stokkel, M.P.M.; Lopez-Yurda, M.; ... ; Haanen, J.B.A.G. (2024)

Article / Letter to editor

Purpose: The aims of this study were to investigate whether (early) PERCIST response monitoring with F-18-FDG PET/CT is predictive for progression-free survival (PFS) in unresectable stage III or IV melanoma patients treated with BRAF/MEK inhibitor (MEKi) and to define dissemination patterns at progression with a lesion-based evaluation in direct comparison to baseline to improve our understanding of F-18-FDG PET/CT during BRAF/MEKi.Patients and methods: This prospective multicenter single-arm study included 70 patients with unresectable stage III/IV BRAF-mutated melanoma who underwent contrast-enhanced CT and F-18-FDG PET/CT at baseline and 2 and 7 weeks during treatment with vemurafenib plus cobimetinib and at progression if possible. Tumor response assessment was done with RECIST1.1 and PERCIST. Follow-up PET/CT scans were visually compared with baseline to assess dissemination patterns.Results: Using RECIST1.1, PFS was not significantly different between the response groups (P = 0.26). At 2 weeks, PERCIST median PFS was 15.7 months for patients with complete metabolic response (CMR) versus 8.3 months for non-CMR (P = 0.035). The hazards ratio (HR) for progression/death in non-CMR versus CMR was 1.99 (95% confidence interval [CI], 1.03-3.84; P = 0.040) and 1.77 (95% CI, 0.91-3.43; P = 0.0935) when adjusting for lactate dehydrogenase (LDH). At 7 weeks, median PFS for PERCIST CMR was 16.7 months versus 8.5 months for non-CMR (P = 0.0003). The HR for progression/death in the non-CMR group was significantly increased (HR, 2.94; 95% CI, 1.60-5.40; P = 0.0005), even when adjusting for LDH (HR, 2.65; 95% CI, 1.43-4.91; P = 0.0020). At week 7, F-18-FDG PET/CT was false-positive in all 4 (6%) patients with new FDG-avid lesions but CMR of known metastases. When F-18-FDG PET/CT was performed at progressive disease, 18/22 (82%) patients had progression of known metastases with or without new F-18-FDG-avid lesions.Conclusions: This study shows that PERCIST response assessment at week 7 is predictive for PFS, regardless of LDH. At 2 weeks, patients with CMR have longer PFS than patients with non-CMR, but different PET parameters should be investigated to further evaluate the added value of early F-18-FDG PET/CT. Disease progression on PET/CT is predominated by progression of known metastases, and new F-18-FDG-avid lesions during BRAF/MEKi are not automatically a sign of recurrent disease.

• melanoma
• BRAF mutation
• progression-free survival
• PET
• PERCIST
• targeted therapy

• All authors: Hiel, B. van der; Aalbersberg, E.A.; Eertwegh, A.J.M. van den; Veen, L.J.D.V. de van der; Stokkel, M.P.M.; Lopez-Yurda, M.; Boellaard, R.; Kapiteijn, E.W.; Hospers, G.A.P.; Aarts, M.J.B.; Vos, F.Y.F.L. de; Boers-Sonderen, M.J.; Veldt, A.A.M. van der; Groot, J.W.B. de; Haanen, J.B.A.G.
• Date: 2024-02-01
• Journal: Clinical Nuclear Medicine
• Volume: 49
• Issue: 2
• Pages: 138 - 145
• DOI: doi:10.1097/RLU.0000000000004988