PMID- 33868987
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210421
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - Safety and Tolerability of BRAF Inhibitor and BRAF Inhibitor-Based Combination 
      Therapy in Chinese Patients With Advanced Melanoma: A Real World Study.
PG  - 582676
LID - 10.3389/fonc.2021.582676 [doi]
LID - 582676
AB  - The toxicity spectrum between Chinese and Caucasian patients with melanoma who 
      were treated with BRAF inhibitors (BRAFi) may differ. The purpose of the present 
      study was to assess the safety and tolerability of BRAFi and BRAFi-based 
      combination therapies [MEK inhibitors (MEKi) or anti-programmed death-1 (PD-1) 
      antibody] in Chinese patients with BRAF V600E/K mutation-positive metastatic 
      melanoma. We also investigated whether treatment-related adverse events (AEs) 
      correlated with the prognosis. This retrospective study collected data from 43 
      patients with BRAF V600E/K mutation-positive metastatic melanoma from a single 
      Chinese cancer center. Of the 43 patients, 12 patients received BRAFi 
      monotherapy, 12 patients received BRAFi+MEKi, and 19 patients received BRAFi 
      combined with the anti-PD-1 antibody. The median follow-up time was 19 months. In 
      the BRAFi group, the most common AEs were rashes, palmoplantar 
      erythrodysesthesia, and arthralgia. Four out of 12 (30%) patients experienced 
      grade 3-4 treatment-related AEs. All grades of AEs in the BRAFi+MEKi group were 
      similar to the BRAFi group, except for higher pyrexia (58.3%) and fewer cutaneous 
      AEs. Three out of 12 (25%) patients experienced grade 3-4 AEs, especially pyrexia 
      (16.7%). In the BRAFi+anti-PD-1 antibody group, AEs were similar to the BRAFi 
      group, except for an increased aminotransferase level (36.8%), increased 
      bilirubin (31.6%), and hypothyroidism (15.8%). Eleven out of 19 (57.9%) patients 
      experienced grade 3-4 AEs and four out of 19 (21%) patients discontinued the 
      therapy due to AEs. Treatment-related hepatotoxicity (trHE), defined as an 
      increase in either alanine aminotransferase (ALT), aspartate transaminase (AST), 
      or bilirubin levels, was the only AE identified as a significant poor-prognosis 
      indicator in this study. The median progression-free survival of patients with 
      trHE (41.9%) was 8 months, whereas it was 18 months for those without trHE [p = 
      0.046, hazard ratio (HR) = 2.116]. Moreover, this association was independent of 
      medication regimens (p = 0.014, HR = 2.971). The overall response rate of 
      patients with trHE was significantly lower than those without trHE (44.4 vs. 
      60.0%, p = 0.024), and we observed a similar trend in patients treated with 
      BRAFi, BRAFi+MEKi, and BRAFi+anti-PD-1 antibody. In conclusion, BRAFi and 
      BRAFi-based combination therapies were tolerable with reversible AEs in Chinese 
      patients with melanoma. The trHE in patients receiving BRAFi and BRAFi-based 
      regimens might indicate a poor therapy-related prognosis.
CI  - Copyright (c) 2021 Liu, Li, Ding, Li, Wen, Weng, Wang, Jiang and Zhang.
FAU - Liu, Xing
AU  - Liu X
AD  - Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Li, Jing-Jing
AU  - Li JJ
AD  - Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Ding, Ya
AU  - Ding Y
AD  - Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Li, Dan-Dan
AU  - Li DD
AD  - Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Wen, Xi-Zhi
AU  - Wen XZ
AD  - Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Weng, De-Sheng
AU  - Weng DS
AD  - Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Wang, Jiu-Hong
AU  - Wang JH
AD  - Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Jiang, Hang
AU  - Jiang H
AD  - Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Zhang, Xiao-Shi
AU  - Zhang XS
AD  - Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20210401
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8047100
OTO - NOTNLM
OT  - BRAF inhibitor
OT  - BRAF inhibitor-based combination
OT  - BRAFV600E/K-positive
OT  - China
OT  - advanced melanoma
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/04/20 06:00
MHDA- 2021/04/20 06:01
PMCR- 2021/01/01
CRDT- 2021/04/19 06:32
PHST- 2020/07/13 00:00 [received]
PHST- 2021/02/12 00:00 [accepted]
PHST- 2021/04/19 06:32 [entrez]
PHST- 2021/04/20 06:00 [pubmed]
PHST- 2021/04/20 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.582676 [doi]
PST - epublish
SO  - Front Oncol. 2021 Apr 1;11:582676. doi: 10.3389/fonc.2021.582676. eCollection 
      2021.