BRAF/MEK inhibitor rechallenge in advanced melanoma patients

• DOI: 10.1002/cncr.35178
• Publication Date: 2024-01-10T18:26:56Z
• Authors: Olivier J. Van Not; Alfons J. M. van ...; John B. Haanen; Rozemarijn S. van...; Maureen J. B. Aarts; Franchette W. P. ...; Christian U. Blank; Marye J. Boers‐So...; Jan Willem W. B. ...; Geke A. P. Hospers; Ellen Kapiteijn; Manja Bloem; Djura Piersma; Marion Stevense‐d...; Rik J. Verheijden; Astrid A. M. van ...; Michel W. J. M. W...; Willeke A. M. Blokx; Karijn P. M. Suij...
• Keywords: Proto-Oncogene Proteins B-raf; Mitogen-Activated Protein Kinase Kinases; Cancer Research; response; Brain Neoplasms; rechallenge; targeted therapy; survival; 03 medical and health sciences; 0302 clinical medicine; Oncology; SDG 3 - Good Health and Well-being; Mutation; Journal Article; melanoma; Humans; Medical Oncology - Radboud University Medical Center; Melanoma; Protein Kinase Inhibitors; Retrospective Studies

Abstract Background Effectivity of BRAF(/MEK) inhibitor rechallenge has been described in prior studies. However, structured data are largely lacking. Methods Data from all advanced melanoma patients treated with BRAFi(/MEKi) were retrieved the Dutch Melanoma Treatment Registry. The authors analyzed objective response rate (ORR), progression‐free survival (PFS), and overall (OS) for both first treatment rechallenge. They performed a multivariable logistic regression Cox proportional hazards model to assess factors associated survival. Results included 468 largest cohort date who underwent at least two episodes BRAFi(/MEKi). Following rechallenge, ORR was 43%, median PFS 4.6 months (95% confidence interval [CI], 4.1–5.2), OS 8.2 CI, 7.2–9.4). Median after discontinued due progression 3.1 2.7–4.0) versus 5.2 4.5–5.9) other reasons. Discontinuing lactate dehydrogenase (LDH) levels greater than times upper limit normal lower odds worse OS. Symptomatic brain metastases survival, whereas longer between better Responding not or Conclusions This study confirms that benefit Elevated LDH levels, symptomatic metastases, discontinuing less A prolonged is more