Mutational profiles of metastatic colorectal cancer treated with FOLFIRI plus cetuximab or bevacizumab before and after secondary resection (AIO KRK 0306; FIRE-3).
Adult
Aged
Antineoplastic Agents, Immunological
/ therapeutic use
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Bevacizumab
/ therapeutic use
Biomarkers, Tumor
/ genetics
Camptothecin
/ analogs & derivatives
Cetuximab
/ therapeutic use
Colorectal Neoplasms
/ drug therapy
Female
Fluorouracil
/ therapeutic use
Humans
Leucovorin
/ therapeutic use
Male
Middle Aged
Mutation
Proto-Oncogene Proteins p21(ras)
/ genetics
Retrospective Studies
Treatment Outcome
NGS
bevacizumab
cetuximab
metastatic colorectal cancer
paired samples
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 12 2021
01 12 2021
Historique:
revised:
12
06
2021
received:
27
03
2021
accepted:
28
06
2021
pubmed:
27
7
2021
medline:
11
11
2021
entrez:
26
7
2021
Statut:
ppublish
Résumé
Secondary resection of metastases is recommended in metastatic colorectal cancer (mCRC). Data describing changes in mutational profiles of corresponding primary tumor and metastatic tissue after conversion treatment are limited. Next generation sequencing was performed in formalin-fixed mCRC samples from patients of the FIRE-3 trial (FOLFIRI plus cetuximab or bevacizumab) before treatment start (baseline) and after secondary resection of metastases (post baseline). Changes of mutational profiles and tumor mutational burden (TMB) were assessed within a post-hoc analysis. Median overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were compared between treatment arms. Paired tumor samples were obtained from 25 patients (19 RAS wild-type, 6 RAS mutant by pyrosequencing). ORR (92.0% vs 58.0%) and OS (60.8 vs 35.4 months, hazard ratio = 0.39 [95% CI 0.14-1.12], P = .08) were higher for patients receiving cetuximab. After conversion therapy, 56 alterations (42 in the cetuximab and 14 in the bevacizumab arm) were newly observed in 18 patients (9 each treated with cetuximab or bevacizumab). Gains (n = 21) and losses (n = 21) of alterations occurred during cetuximab-based treatment, while mainly gains of alterations occurred during bevacizumab (n = 10). Three of nine patients treated with cetuximab that presented a change of mutational profiles, developed resistance to cetuximab. Mutational profiles were largely comparable before and after treatment with anti-VEGF or anti-EGFR directed monoclonal antibodies after secondary resection. Mutations associated with resistance to anti-EGFR antibodies were observed in only one-third of patients.
Substances chimiques
Antineoplastic Agents, Immunological
0
Biomarkers, Tumor
0
KRAS protein, human
0
Bevacizumab
2S9ZZM9Q9V
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Cetuximab
PQX0D8J21J
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Camptothecin
XT3Z54Z28A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1935-1943Informations de copyright
© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
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