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?

Bernies van der Hiel*, Else A Aalbersberg, Alfons J M van den Eertwegh, Linda J de Wit-van der Veen, Marcel P M Stokkel, Marta Lopez-Yurda, Ronald Boellaard, Ellen W Kapiteijn, Geke A P Hospers, Maureen J B Aarts, Filip Y F L de Vos, Marye J Boers-Sonderen, Astrid A M van der Veldt, Jan Willem B de Groot, John B A G Haanen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: The aims of this study were to investigate whether (early) PERCIST response monitoring with 18F-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 18F-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 18F-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, 18F-FDG PET/CT was false-positive in all 4 (6%) patients with new FDG-avid lesions but CMR of known metastases. When 18F-FDG PET/CT was performed at progressive disease, 18/22 (82%) patients had progression of known metastases with or without new 18F-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 18F-FDG PET/CT. Disease progression on PET/CT is predominated by progression of known metastases, and new 18F-FDG-avid lesions during BRAF/MEKi are not automatically a sign of recurrent disease.

Original languageEnglish
Pages (from-to)138-145
Number of pages8
JournalClinical Nuclear Medicine
Volume49
Issue number2
Early online date19 Dec 2023
DOIs
Publication statusPublished - 1 Feb 2024

Keywords

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

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