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Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study

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Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study. / Bai, Xue; Shaheen, Ahmed; Grieco, Charlotte; d'Arienzo, Paolo D; Mina, Florentia; Czapla, Juliane A; Lawless, Aleigha R; Bongiovanni, Eleonora; Santaniello, Umberto; Zappi, Helena; Dulak, Dominika; Williamson, Andrew; Lee, Rebecca; Gupta, Avinash; Li, Caili; Si, Lu; Ubaldi, Martina; Yamazaki, Naoya; Ogata, Dai; Johnson, Rebecca; Park, Benjamin C; Jung, Seungyeon; Madonna, Gabriele; Hochherz, Juliane; Umeda, Yoshiyasu; Nakamura, Yasuhiro; Gebhardt, Christoffer; Festino, Lucia; Capone, Mariaelena; Ascierto, Paolo Antonio; Johnson, Douglas B; Lo, Serigne N; Long, Georgina V; Menzies, Alexander M; Namikawa, Kenjiro; Mandala, Mario; Guo, Jun; Lorigan, Paul; Najjar, Yana G; Haydon, Andrew; Quaglino, Pietro; Boland, Genevieve M; Sullivan, Ryan J; Furness, Andrew J S; Plummer, Ruth; Flaherty, Keith T.

In: ECLINICALMEDICINE, Vol. 65, 11.2023, p. 102290.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Bai, X, Shaheen, A, Grieco, C, d'Arienzo, PD, Mina, F, Czapla, JA, Lawless, AR, Bongiovanni, E, Santaniello, U, Zappi, H, Dulak, D, Williamson, A, Lee, R, Gupta, A, Li, C, Si, L, Ubaldi, M, Yamazaki, N, Ogata, D, Johnson, R, Park, BC, Jung, S, Madonna, G, Hochherz, J, Umeda, Y, Nakamura, Y, Gebhardt, C, Festino, L, Capone, M, Ascierto, PA, Johnson, DB, Lo, SN, Long, GV, Menzies, AM, Namikawa, K, Mandala, M, Guo, J, Lorigan, P, Najjar, YG, Haydon, A, Quaglino, P, Boland, GM, Sullivan, RJ, Furness, AJS, Plummer, R & Flaherty, KT 2023, 'Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study', ECLINICALMEDICINE, vol. 65, pp. 102290. https://doi.org/10.1016/j.eclinm.2023.102290

APA

Bai, X., Shaheen, A., Grieco, C., d'Arienzo, P. D., Mina, F., Czapla, J. A., Lawless, A. R., Bongiovanni, E., Santaniello, U., Zappi, H., Dulak, D., Williamson, A., Lee, R., Gupta, A., Li, C., Si, L., Ubaldi, M., Yamazaki, N., Ogata, D., ... Flaherty, K. T. (2023). Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study. ECLINICALMEDICINE, 65, 102290. https://doi.org/10.1016/j.eclinm.2023.102290

Vancouver

Bai X, Shaheen A, Grieco C, d'Arienzo PD, Mina F, Czapla JA et al. Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study. ECLINICALMEDICINE. 2023 Nov;65:102290. https://doi.org/10.1016/j.eclinm.2023.102290

Bibtex

@article{32774662334947cf9cc08dca37ce5602,
title = "Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study",
abstract = "BACKGROUND: Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III BRAF V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers.METHODS: This multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, and US. We included adult patients with resected stage III BRAF V600-mutant melanoma who received either adjuvant D/T or PD-1 between Jul 2015 and Oct 2022. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS), recurrence pattern and toxicity.FINDINGS: We included 598 patients with stage III BRAF V600-mutant melanoma who received either adjuvant D/T (n = 393 [66%]) or PD-1 (n = 205 [34%]) post definitive surgery between Jul 2015 and Oct 2022. At a median follow-up of 33 months (IQR 21-43), the median RFS was 51.0 months (95% CI 41.0-not reached [NR]) in the D/T group, significantly longer than PD-1 (44.8 months [95% CI 28.5-NR]) (univariate: HR 0.66, 95% CI 0.50-0.87, P = 0.003; multivariate: HR 0.58, 95% CI 0.39-0.86, P = 0.007), with comparable OS with PD-1 (multivariate, HR 0.90, 95% CI 0.48-1.70, P = 0.75). Similar findings were observed using a restricted-mean-survival-time model. Among those who experienced recurrence, the proportion of distant metastases was higher in the D/T cohort. D/T had a higher incidence of treatment modification due to adverse events (AEs) than PD-1, but fewer persistent AEs.INTERPRETATION: In patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T seems to provide a better outcome compared with PD-1, but a longer follow-up and ideally a large prospective trial are needed.FUNDING: Dr. Xue Bai was supported by the Beijing Hospitals Authority Youth Programme (QMS20211101) for her efforts devoted to this study. Dr. Keith T. Flaherty was funded by Adelson Medical Research Foundation for the efforts devoted to this study.",
author = "Xue Bai and Ahmed Shaheen and Charlotte Grieco and d'Arienzo, {Paolo D} and Florentia Mina and Czapla, {Juliane A} and Lawless, {Aleigha R} and Eleonora Bongiovanni and Umberto Santaniello and Helena Zappi and Dominika Dulak and Andrew Williamson and Rebecca Lee and Avinash Gupta and Caili Li and Lu Si and Martina Ubaldi and Naoya Yamazaki and Dai Ogata and Rebecca Johnson and Park, {Benjamin C} and Seungyeon Jung and Gabriele Madonna and Juliane Hochherz and Yoshiyasu Umeda and Yasuhiro Nakamura and Christoffer Gebhardt and Lucia Festino and Mariaelena Capone and Ascierto, {Paolo Antonio} and Johnson, {Douglas B} and Lo, {Serigne N} and Long, {Georgina V} and Menzies, {Alexander M} and Kenjiro Namikawa and Mario Mandala and Jun Guo and Paul Lorigan and Najjar, {Yana G} and Andrew Haydon and Pietro Quaglino and Boland, {Genevieve M} and Sullivan, {Ryan J} and Furness, {Andrew J S} and Ruth Plummer and Flaherty, {Keith T}",
note = "{\textcopyright} 2023 The Author(s).",
year = "2023",
month = nov,
doi = "10.1016/j.eclinm.2023.102290",
language = "English",
volume = "65",
pages = "102290",
journal = "ECLINICALMEDICINE",
issn = "2589-5370",
publisher = "Lancet Publishing Group",

}

RIS

TY - JOUR

T1 - Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study

AU - Bai, Xue

AU - Shaheen, Ahmed

AU - Grieco, Charlotte

AU - d'Arienzo, Paolo D

AU - Mina, Florentia

AU - Czapla, Juliane A

AU - Lawless, Aleigha R

AU - Bongiovanni, Eleonora

AU - Santaniello, Umberto

AU - Zappi, Helena

AU - Dulak, Dominika

AU - Williamson, Andrew

AU - Lee, Rebecca

AU - Gupta, Avinash

AU - Li, Caili

AU - Si, Lu

AU - Ubaldi, Martina

AU - Yamazaki, Naoya

AU - Ogata, Dai

AU - Johnson, Rebecca

AU - Park, Benjamin C

AU - Jung, Seungyeon

AU - Madonna, Gabriele

AU - Hochherz, Juliane

AU - Umeda, Yoshiyasu

AU - Nakamura, Yasuhiro

AU - Gebhardt, Christoffer

AU - Festino, Lucia

AU - Capone, Mariaelena

AU - Ascierto, Paolo Antonio

AU - Johnson, Douglas B

AU - Lo, Serigne N

AU - Long, Georgina V

AU - Menzies, Alexander M

AU - Namikawa, Kenjiro

AU - Mandala, Mario

AU - Guo, Jun

AU - Lorigan, Paul

AU - Najjar, Yana G

AU - Haydon, Andrew

AU - Quaglino, Pietro

AU - Boland, Genevieve M

AU - Sullivan, Ryan J

AU - Furness, Andrew J S

AU - Plummer, Ruth

AU - Flaherty, Keith T

N1 - © 2023 The Author(s).

PY - 2023/11

Y1 - 2023/11

N2 - BACKGROUND: Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III BRAF V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers.METHODS: This multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, and US. We included adult patients with resected stage III BRAF V600-mutant melanoma who received either adjuvant D/T or PD-1 between Jul 2015 and Oct 2022. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS), recurrence pattern and toxicity.FINDINGS: We included 598 patients with stage III BRAF V600-mutant melanoma who received either adjuvant D/T (n = 393 [66%]) or PD-1 (n = 205 [34%]) post definitive surgery between Jul 2015 and Oct 2022. At a median follow-up of 33 months (IQR 21-43), the median RFS was 51.0 months (95% CI 41.0-not reached [NR]) in the D/T group, significantly longer than PD-1 (44.8 months [95% CI 28.5-NR]) (univariate: HR 0.66, 95% CI 0.50-0.87, P = 0.003; multivariate: HR 0.58, 95% CI 0.39-0.86, P = 0.007), with comparable OS with PD-1 (multivariate, HR 0.90, 95% CI 0.48-1.70, P = 0.75). Similar findings were observed using a restricted-mean-survival-time model. Among those who experienced recurrence, the proportion of distant metastases was higher in the D/T cohort. D/T had a higher incidence of treatment modification due to adverse events (AEs) than PD-1, but fewer persistent AEs.INTERPRETATION: In patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T seems to provide a better outcome compared with PD-1, but a longer follow-up and ideally a large prospective trial are needed.FUNDING: Dr. Xue Bai was supported by the Beijing Hospitals Authority Youth Programme (QMS20211101) for her efforts devoted to this study. Dr. Keith T. Flaherty was funded by Adelson Medical Research Foundation for the efforts devoted to this study.

AB - BACKGROUND: Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III BRAF V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers.METHODS: This multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, and US. We included adult patients with resected stage III BRAF V600-mutant melanoma who received either adjuvant D/T or PD-1 between Jul 2015 and Oct 2022. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS), recurrence pattern and toxicity.FINDINGS: We included 598 patients with stage III BRAF V600-mutant melanoma who received either adjuvant D/T (n = 393 [66%]) or PD-1 (n = 205 [34%]) post definitive surgery between Jul 2015 and Oct 2022. At a median follow-up of 33 months (IQR 21-43), the median RFS was 51.0 months (95% CI 41.0-not reached [NR]) in the D/T group, significantly longer than PD-1 (44.8 months [95% CI 28.5-NR]) (univariate: HR 0.66, 95% CI 0.50-0.87, P = 0.003; multivariate: HR 0.58, 95% CI 0.39-0.86, P = 0.007), with comparable OS with PD-1 (multivariate, HR 0.90, 95% CI 0.48-1.70, P = 0.75). Similar findings were observed using a restricted-mean-survival-time model. Among those who experienced recurrence, the proportion of distant metastases was higher in the D/T cohort. D/T had a higher incidence of treatment modification due to adverse events (AEs) than PD-1, but fewer persistent AEs.INTERPRETATION: In patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T seems to provide a better outcome compared with PD-1, but a longer follow-up and ideally a large prospective trial are needed.FUNDING: Dr. Xue Bai was supported by the Beijing Hospitals Authority Youth Programme (QMS20211101) for her efforts devoted to this study. Dr. Keith T. Flaherty was funded by Adelson Medical Research Foundation for the efforts devoted to this study.

U2 - 10.1016/j.eclinm.2023.102290

DO - 10.1016/j.eclinm.2023.102290

M3 - SCORING: Journal article

C2 - 37965433

VL - 65

SP - 102290

JO - ECLINICALMEDICINE

JF - ECLINICALMEDICINE

SN - 2589-5370

ER -