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Liquid Biopsy and Radiological Response Predict Outcomes Following Discontinuation of Targeted Therapy in Patients with BRAF Mutated Melanoma

BACKGROUND: Outcomes of patients with metastatic melanoma discontinuing BRAF‐targeted therapy for cumulative toxicity after sustained response are unknown. MATERIALS AND METHODS: This retrospective case series analysis conducted at a single Cancer Center in Italy included patients with BRAF mutated...

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Autores principales: Di Guardo, Lorenza, Randon, Giovanni, Corti, Francesca, Vallacchi, Viviana, Raimondi, Alessandra, Fucà, Giovanni, Bini, Marta, Maurichi, Andrea, Patuzzo, Roberto, Gallino, Gianfrancesco, Mattavelli, Ilaria, Ruggeri, Roberta, Angi, Martina, Cossa, Mara, Valeri, Barbara, Cimminiello, Carolina, Santinami, Mario, Rivoltini, Licia, de Braud, Filippo, Rodolfo, Monica, Vecchio, Michele Del
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649022/
https://www.ncbi.nlm.nih.gov/pubmed/34355463
http://dx.doi.org/10.1002/onco.13926
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author Di Guardo, Lorenza
Randon, Giovanni
Corti, Francesca
Vallacchi, Viviana
Raimondi, Alessandra
Fucà, Giovanni
Bini, Marta
Maurichi, Andrea
Patuzzo, Roberto
Gallino, Gianfrancesco
Mattavelli, Ilaria
Ruggeri, Roberta
Angi, Martina
Cossa, Mara
Valeri, Barbara
Cimminiello, Carolina
Santinami, Mario
Rivoltini, Licia
de Braud, Filippo
Rodolfo, Monica
Vecchio, Michele Del
author_facet Di Guardo, Lorenza
Randon, Giovanni
Corti, Francesca
Vallacchi, Viviana
Raimondi, Alessandra
Fucà, Giovanni
Bini, Marta
Maurichi, Andrea
Patuzzo, Roberto
Gallino, Gianfrancesco
Mattavelli, Ilaria
Ruggeri, Roberta
Angi, Martina
Cossa, Mara
Valeri, Barbara
Cimminiello, Carolina
Santinami, Mario
Rivoltini, Licia
de Braud, Filippo
Rodolfo, Monica
Vecchio, Michele Del
author_sort Di Guardo, Lorenza
collection PubMed
description BACKGROUND: Outcomes of patients with metastatic melanoma discontinuing BRAF‐targeted therapy for cumulative toxicity after sustained response are unknown. MATERIALS AND METHODS: This retrospective case series analysis conducted at a single Cancer Center in Italy included patients with BRAF mutated metastatic melanoma treated with a BRAF inhibitor as a single agent or in combination with a MEK inhibitor between June 1, 2011 and January 1, 2020 and interrupted treatment due to cumulative toxicity after achieving complete response (CR) or long‐lasting partial response (PR; i.e. >12 months). RESULTS: We included 24 patients with a median treatment duration of 59.4 months (95% confidence interval [CI], 55.4–63.4; range, 12–88). CR and PR were achieved in 71% and 29% of patients, respectively. At a median follow‐up after treatment discontinuation of 37.8 months (95% CI, 33.7–41.9), the 12‐month progression‐free survival after discontinuation (dPFS) rate was 70.8% (95% CI 54.8–91.6) and 24‐month dPFS rate was 58.3% (95% CI, 41.6–81.8). Baseline patient and tumor characteristics as well as treatment duration and best response did not significantly impact on dPFS. Patients with CR and negative circulating tumor DNA (ctDNA) at time of discontinuation had a significantly improved dPFS compared with patients with either radiological residual disease or ctDNA positivity (p = .007). No patient in CR with undetectable ctDNA experienced progression. CONCLUSION: The risk of progression is high even in patients with sustained sensitivity to BRAF/MEK inhibitors. Integration of liquid biopsy in clinical trials investigating the optimal management of patients with sustained sensitivity to BRAF/MEK inhibitors is warranted. IMPLICATIONS FOR PRACTICE: Outcomes of patients with metastatic melanoma discontinuing BRAF‐targeted therapy for cumulative toxicity are unknown. This study analyzed patients with sustained responses (median treatment duration 59.4 months). Twelve‐ and 24‐month progression‐free survival following discontinuation were 70.8% and 58.3%, respectively. Complete response and negative circulating tumor DNA at time of discontinuation are promising prognostic biomarkers in this setting.
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spelling pubmed-86490222021-12-20 Liquid Biopsy and Radiological Response Predict Outcomes Following Discontinuation of Targeted Therapy in Patients with BRAF Mutated Melanoma Di Guardo, Lorenza Randon, Giovanni Corti, Francesca Vallacchi, Viviana Raimondi, Alessandra Fucà, Giovanni Bini, Marta Maurichi, Andrea Patuzzo, Roberto Gallino, Gianfrancesco Mattavelli, Ilaria Ruggeri, Roberta Angi, Martina Cossa, Mara Valeri, Barbara Cimminiello, Carolina Santinami, Mario Rivoltini, Licia de Braud, Filippo Rodolfo, Monica Vecchio, Michele Del Oncologist Melanoma and Cutaneous Malignancies BACKGROUND: Outcomes of patients with metastatic melanoma discontinuing BRAF‐targeted therapy for cumulative toxicity after sustained response are unknown. MATERIALS AND METHODS: This retrospective case series analysis conducted at a single Cancer Center in Italy included patients with BRAF mutated metastatic melanoma treated with a BRAF inhibitor as a single agent or in combination with a MEK inhibitor between June 1, 2011 and January 1, 2020 and interrupted treatment due to cumulative toxicity after achieving complete response (CR) or long‐lasting partial response (PR; i.e. >12 months). RESULTS: We included 24 patients with a median treatment duration of 59.4 months (95% confidence interval [CI], 55.4–63.4; range, 12–88). CR and PR were achieved in 71% and 29% of patients, respectively. At a median follow‐up after treatment discontinuation of 37.8 months (95% CI, 33.7–41.9), the 12‐month progression‐free survival after discontinuation (dPFS) rate was 70.8% (95% CI 54.8–91.6) and 24‐month dPFS rate was 58.3% (95% CI, 41.6–81.8). Baseline patient and tumor characteristics as well as treatment duration and best response did not significantly impact on dPFS. Patients with CR and negative circulating tumor DNA (ctDNA) at time of discontinuation had a significantly improved dPFS compared with patients with either radiological residual disease or ctDNA positivity (p = .007). No patient in CR with undetectable ctDNA experienced progression. CONCLUSION: The risk of progression is high even in patients with sustained sensitivity to BRAF/MEK inhibitors. Integration of liquid biopsy in clinical trials investigating the optimal management of patients with sustained sensitivity to BRAF/MEK inhibitors is warranted. IMPLICATIONS FOR PRACTICE: Outcomes of patients with metastatic melanoma discontinuing BRAF‐targeted therapy for cumulative toxicity are unknown. This study analyzed patients with sustained responses (median treatment duration 59.4 months). Twelve‐ and 24‐month progression‐free survival following discontinuation were 70.8% and 58.3%, respectively. Complete response and negative circulating tumor DNA at time of discontinuation are promising prognostic biomarkers in this setting. John Wiley & Sons, Inc. 2021-09-21 2021-12 /pmc/articles/PMC8649022/ /pubmed/34355463 http://dx.doi.org/10.1002/onco.13926 Text en © 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Melanoma and Cutaneous Malignancies
Di Guardo, Lorenza
Randon, Giovanni
Corti, Francesca
Vallacchi, Viviana
Raimondi, Alessandra
Fucà, Giovanni
Bini, Marta
Maurichi, Andrea
Patuzzo, Roberto
Gallino, Gianfrancesco
Mattavelli, Ilaria
Ruggeri, Roberta
Angi, Martina
Cossa, Mara
Valeri, Barbara
Cimminiello, Carolina
Santinami, Mario
Rivoltini, Licia
de Braud, Filippo
Rodolfo, Monica
Vecchio, Michele Del
Liquid Biopsy and Radiological Response Predict Outcomes Following Discontinuation of Targeted Therapy in Patients with BRAF Mutated Melanoma
title Liquid Biopsy and Radiological Response Predict Outcomes Following Discontinuation of Targeted Therapy in Patients with BRAF Mutated Melanoma
title_full Liquid Biopsy and Radiological Response Predict Outcomes Following Discontinuation of Targeted Therapy in Patients with BRAF Mutated Melanoma
title_fullStr Liquid Biopsy and Radiological Response Predict Outcomes Following Discontinuation of Targeted Therapy in Patients with BRAF Mutated Melanoma
title_full_unstemmed Liquid Biopsy and Radiological Response Predict Outcomes Following Discontinuation of Targeted Therapy in Patients with BRAF Mutated Melanoma
title_short Liquid Biopsy and Radiological Response Predict Outcomes Following Discontinuation of Targeted Therapy in Patients with BRAF Mutated Melanoma
title_sort liquid biopsy and radiological response predict outcomes following discontinuation of targeted therapy in patients with braf mutated melanoma
topic Melanoma and Cutaneous Malignancies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649022/
https://www.ncbi.nlm.nih.gov/pubmed/34355463
http://dx.doi.org/10.1002/onco.13926
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