TY - JOUR
T1 - BRAF/MEK inhibitor rechallenge in advanced melanoma patients
AU - van Not, Olivier J.
AU - van den Eertwegh, Alfons J. M.
AU - Haanen, John B.
AU - van Rijn, Rozemarijn S.
AU - Aarts, Maureen J. B.
AU - van den Berkmortel, Franchette W. P. J.
AU - Blank, Christian U.
AU - Boers-Sonderen, Marye J.
AU - de Groot, Jan Willem W. B.
AU - Hospers, Geke A. P.
AU - Kapiteijn, Ellen
AU - Bloem, Manja
AU - Piersma, Djura
AU - Stevense-den Boer, Marion
AU - Verheijden, Rik J.
AU - van der Veldt, Astrid A. M.
AU - Wouters, Michel W. J. M.
AU - Blokx, Willeke A. M.
AU - Suijkerbuijk, Karijn P. M.
N1 - Funding Information: For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing foundation received a start‐up grant from governmental organization The Netherlands Organization for Health Research and Development (ZonMW, project number 836002002). The DMTR is structurally funded by Bristol‐Myers Squibb, Merck Sharpe & Dohme, Novartis, and Roche Pharma. Roche Pharma stopped funding in 2019, and Pierre Fabre started funding the DMTR in 2019. For this work, no funding was granted. The medical ethical committee approved research using DMTR data and concluded that it was not deemed subject to the Medical Research Involving Human Subjects Act in compliance with Dutch regulations. Publisher Copyright: © 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.
PY - 2024
Y1 - 2024
N2 - 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) rechallenge were retrieved from the Dutch Melanoma Treatment Registry. The authors analyzed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for both first treatment and rechallenge. They performed a multivariable logistic regression and a multivariable Cox proportional hazards model to assess factors associated with response and survival. Results: The authors included 468 patients in the largest cohort to date who underwent at least two treatment episodes of BRAFi(/MEKi). Following rechallenge, ORR was 43%, median PFS was 4.6 months (95% confidence interval [CI], 4.1–5.2), and median OS was 8.2 months (95% CI, 7.2–9.4). Median PFS after rechallenge for patients who discontinued first BRAFi(/MEKi) treatment due to progression was 3.1 months (95% CI, 2.7–4.0) versus 5.2 months (95% CI, 4.5–5.9) for patients who discontinued treatment for other reasons. Discontinuing first treatment due to progression and lactate dehydrogenase (LDH) levels greater than two times the upper limit of normal were associated with lower odds of response and worse PFS and OS. Symptomatic brain metastases were associated with worse survival, whereas a longer treatment interval between first treatment and rechallenge was associated with better survival. Responding to the first BRAFi(/MEKi) treatment was not associated with response or survival. Conclusions: This study confirms that patients benefit from rechallenge. Elevated LDH levels, symptomatic brain metastases, and discontinuing first BRAFi(/MEKi) treatment due to progression are associated with less benefit from rechallenge. A prolonged treatment interval is associated with more benefit from rechallenge.
AB - 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) rechallenge were retrieved from the Dutch Melanoma Treatment Registry. The authors analyzed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for both first treatment and rechallenge. They performed a multivariable logistic regression and a multivariable Cox proportional hazards model to assess factors associated with response and survival. Results: The authors included 468 patients in the largest cohort to date who underwent at least two treatment episodes of BRAFi(/MEKi). Following rechallenge, ORR was 43%, median PFS was 4.6 months (95% confidence interval [CI], 4.1–5.2), and median OS was 8.2 months (95% CI, 7.2–9.4). Median PFS after rechallenge for patients who discontinued first BRAFi(/MEKi) treatment due to progression was 3.1 months (95% CI, 2.7–4.0) versus 5.2 months (95% CI, 4.5–5.9) for patients who discontinued treatment for other reasons. Discontinuing first treatment due to progression and lactate dehydrogenase (LDH) levels greater than two times the upper limit of normal were associated with lower odds of response and worse PFS and OS. Symptomatic brain metastases were associated with worse survival, whereas a longer treatment interval between first treatment and rechallenge was associated with better survival. Responding to the first BRAFi(/MEKi) treatment was not associated with response or survival. Conclusions: This study confirms that patients benefit from rechallenge. Elevated LDH levels, symptomatic brain metastases, and discontinuing first BRAFi(/MEKi) treatment due to progression are associated with less benefit from rechallenge. A prolonged treatment interval is associated with more benefit from rechallenge.
KW - melanoma
KW - rechallenge
KW - response
KW - survival
KW - targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85181942238&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/cncr.35178
DO - https://doi.org/10.1002/cncr.35178
M3 - Article
C2 - 38198485
SN - 0008-543X
VL - 130
SP - 1673
EP - 1683
JO - Cancer
JF - Cancer
IS - 9
ER -