Reinduction of an Anti-EGFR-based First-line Regimen in Patients with RAS Wild-type Metastatic Colorectal Cancer Enrolled in the Valentino Study.
anti-EGFR
chemotherapy
metastatic colorectal cancer
reinduction
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
03 02 2022
03 02 2022
Historique:
received:
15
06
2021
accepted:
17
11
2021
entrez:
19
3
2022
pubmed:
20
3
2022
medline:
21
4
2022
Statut:
ppublish
Résumé
In patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC), growing evidence supports anti-epidermal growth factor receptor (EGFR) retreatment, whereas little is known on the outcomes of anti-EGFR-based reinduction therapy during the upfront strategy. We included patients enrolled in the Valentino study who had disease progression and received at least one dose of post-progression therapy. The Kaplan-Meier method and Cox proportional hazards regression were used for the survival analysis. When comparing the outcomes of anti-EGFR-based reinduction versus any second line, a propensity score-based matching was used. Liver-limited/single site of disease (P < .001 and P = .002), left-sidedness (P = .029), surgery of metastases (P = .003), early tumor shrinkage, and deeper responses (P = .018 and P = .036) were associated with the use of anti-EGFR-based reinduction versus any other second line. All patients treated with reinduction had an anti-EGFR-free interval of at least 3 months. In the propensity score-matched population, progression-free survival (PFS) was similar in the 2 treatment groups, the overall survival (OS) was significantly longer for patients treated with reinduction (P = .029), and the response rate was higher in patients treated with reinduction (P = .033). An oxaliplatin-free interval ≥12 months, left-sidedness, and molecular hyperselection beyond RAS/BRAF were associated with significantly better outcomes after anti-EGFR-based reinduction. Reinduction strategies with anti-EGFR-based regimens are commonly used in clinical practice. Our data highlight the importance of clinical-molecular selection for re-treatments and the need for prospective strategy trials in selected populations.
Sections du résumé
BACKGROUND
In patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC), growing evidence supports anti-epidermal growth factor receptor (EGFR) retreatment, whereas little is known on the outcomes of anti-EGFR-based reinduction therapy during the upfront strategy.
METHODS
We included patients enrolled in the Valentino study who had disease progression and received at least one dose of post-progression therapy. The Kaplan-Meier method and Cox proportional hazards regression were used for the survival analysis. When comparing the outcomes of anti-EGFR-based reinduction versus any second line, a propensity score-based matching was used.
RESULTS
Liver-limited/single site of disease (P < .001 and P = .002), left-sidedness (P = .029), surgery of metastases (P = .003), early tumor shrinkage, and deeper responses (P = .018 and P = .036) were associated with the use of anti-EGFR-based reinduction versus any other second line. All patients treated with reinduction had an anti-EGFR-free interval of at least 3 months. In the propensity score-matched population, progression-free survival (PFS) was similar in the 2 treatment groups, the overall survival (OS) was significantly longer for patients treated with reinduction (P = .029), and the response rate was higher in patients treated with reinduction (P = .033). An oxaliplatin-free interval ≥12 months, left-sidedness, and molecular hyperselection beyond RAS/BRAF were associated with significantly better outcomes after anti-EGFR-based reinduction.
CONCLUSIONS
Reinduction strategies with anti-EGFR-based regimens are commonly used in clinical practice. Our data highlight the importance of clinical-molecular selection for re-treatments and the need for prospective strategy trials in selected populations.
Identifiants
pubmed: 35305093
pii: 6515012
doi: 10.1093/oncolo/oyab012
pmc: PMC8842305
doi:
Substances chimiques
Panitumumab
6A901E312A
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e29-e36Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of AlphaMed Press.
Références
J Clin Oncol. 2006 Jan 20;24(3):394-400
pubmed: 16421419
Br J Cancer. 2018 Apr;118(7):955-965
pubmed: 29531324
Eur J Cancer. 2021 Feb;144:31-40
pubmed: 33321462
Eur J Cancer. 2019 Sep;119:158-167
pubmed: 31445198
Nature. 2012 Jun 28;486(7404):532-6
pubmed: 22722830
Lancet Oncol. 2015 Oct;16(13):1355-69
pubmed: 26361971
Eur J Cancer. 2018 Sep;101:263-272
pubmed: 30054049
Eur J Cancer. 2020 Aug;135:230-239
pubmed: 32623288
Lancet Oncol. 2014 May;15(6):631-9
pubmed: 24703531
Int J Cancer. 2019 Jul 15;145(2):576-585
pubmed: 30614531
Lancet. 2015 May 9;385(9980):1843-52
pubmed: 25862517
Nature. 2012 Jun 28;486(7404):537-40
pubmed: 22722843
Stat Med. 2014 Mar 30;33(7):1242-58
pubmed: 24122911
JAMA Oncol. 2019 Mar 1;5(3):343-350
pubmed: 30476968
Ann Oncol. 2007 Jan;18(1):77-81
pubmed: 17030548
J Clin Oncol. 2019 Nov 20;37(33):3099-3110
pubmed: 31539295
J Clin Oncol. 2015 Nov 10;33(32):3718-26
pubmed: 26261259
Nat Med. 2015 Jul;21(7):795-801
pubmed: 26030179
Clin Colorectal Cancer. 2020 Sep;19(3):191-199.e6
pubmed: 32466976
JAMA Oncol. 2019 Sep 1;5(9):1268-1275
pubmed: 31268481