TY - JOUR
T1 - Pathological response and survival with neoadjuvant therapy in melanoma
T2 - a pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC)
AU - Menzies, Alexander M.
AU - Amaria, Rodabe N.
AU - Rozeman, Elisa A.
AU - Huang, Alexander C.
AU - Tetzlaff, Michael T.
AU - van de Wiel, Bart A.
AU - Lo, Serigne
AU - Tarhini, Ahmad A.
AU - Burton, Elizabeth M.
AU - Pennington, Thomas E.
AU - Saw, Robyn P.M.
AU - Xu, Xiaowei
AU - Karakousis, Giorgos C.
AU - Ascierto, Paolo A.
AU - Spillane, Andrew J.
AU - van Akkooi, Alexander C.J.
AU - Davies, Michael A.
AU - Mitchell, Tara C.
AU - Tawbi, Hussein A.
AU - Scolyer, Richard A.
AU - Wargo, Jennifer A.
AU - Blank, Christian U.
AU - Long, Georgina V.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/2
Y1 - 2021/2
N2 - The association among pathological response, recurrence-free survival (RFS) and overall survival (OS) with neoadjuvant therapy in melanoma remains unclear. In this study, we pooled data from six clinical trials of anti-PD-1-based immunotherapy or BRAF/MEK targeted therapy. In total, 192 patients were included; 141 received immunotherapy (104, combination of ipilimumab and nivolumab; 37, anti-PD-1 monotherapy), and 51 received targeted therapy. A pathological complete response (pCR) occurred in 40% of patients: 47% with targeted therapy and 33% with immunotherapy (43% combination and 20% monotherapy). pCR correlated with improved RFS (pCR 2-year 89% versus no pCR 50%, P < 0.001) and OS (pCR 2-year OS 95% versus no pCR 83%, P = 0.027). In patients with pCR, near pCR or partial pathological response with immunotherapy, very few relapses were seen (2-year RFS 96%), and, at this writing, no patient has died from melanoma, whereas, even with pCR from targeted therapy, the 2-year RFS was only 79%, and OS was only 91%. Pathological response should be an early surrogate endpoint for clinical trials and a new benchmark for development and approval in melanoma.
AB - The association among pathological response, recurrence-free survival (RFS) and overall survival (OS) with neoadjuvant therapy in melanoma remains unclear. In this study, we pooled data from six clinical trials of anti-PD-1-based immunotherapy or BRAF/MEK targeted therapy. In total, 192 patients were included; 141 received immunotherapy (104, combination of ipilimumab and nivolumab; 37, anti-PD-1 monotherapy), and 51 received targeted therapy. A pathological complete response (pCR) occurred in 40% of patients: 47% with targeted therapy and 33% with immunotherapy (43% combination and 20% monotherapy). pCR correlated with improved RFS (pCR 2-year 89% versus no pCR 50%, P < 0.001) and OS (pCR 2-year OS 95% versus no pCR 83%, P = 0.027). In patients with pCR, near pCR or partial pathological response with immunotherapy, very few relapses were seen (2-year RFS 96%), and, at this writing, no patient has died from melanoma, whereas, even with pCR from targeted therapy, the 2-year RFS was only 79%, and OS was only 91%. Pathological response should be an early surrogate endpoint for clinical trials and a new benchmark for development and approval in melanoma.
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U2 - 10.1038/s41591-020-01188-3
DO - 10.1038/s41591-020-01188-3
M3 - Article
C2 - 33558722
AN - SCOPUS:85100662461
SN - 1078-8956
VL - 27
SP - 301
EP - 309
JO - Nature medicine
JF - Nature medicine
IS - 2
ER -