Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08.
Adenocarcinoma
/ drug therapy
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Cetuximab
/ administration & dosage
Chemotherapy, Adjuvant
Colorectal Neoplasms
/ drug therapy
Female
Humans
Irinotecan
/ administration & dosage
Male
Middle Aged
Neoplasm Metastasis
Proto-Oncogene Proteins p21(ras)
/ genetics
Salvage Therapy
Survival Analysis
Treatment Outcome
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
30
03
2020
accepted:
14
08
2020
revised:
28
07
2020
pubmed:
31
8
2020
medline:
25
3
2021
entrez:
1
9
2020
Statut:
ppublish
Résumé
Regorafenib or trifluridine/tipiracil as third-line treatment have limited efficacy in metastatic colorectal cancer (mCRC). This Phase 2 trial evaluated the efficacy and safety of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type mCRC patients who achieved clinical benefit with first-line cetuximab-containing therapy. The primary endpoint was 3-month progression-free survival (PFS) rate. A sample size was calculated; 30 patients with a 3-month PFS rate of 45% deemed promising and 15% unacceptable. Patients with greater and less than the cut-off value of cetuximab-free intervals (CFIs) were classified into the long and short CFI groups, respectively, in subgroup analyses. Among 34 eligible patients who received treatment at least once, 3-month PFS rate was 44.1% (95% confidence interval, 27.4-60.8%). The median PFS and overall survival (OS) were 2.4 and 8.2 months, respectively. The response and disease control rates were 2.9 and 55.9%, respectively. PFS and OS were significantly longer in the long- than in the short CFI group. Irinotecan plus cetuximab rechallenge as third-line treatment for KRAS wild-type mCRC was safe and had promising activity, especially in those with a long CFI, warranting further investigation in a Phase 3 randomised trial. UMIN000010638.
Sections du résumé
BACKGROUND
Regorafenib or trifluridine/tipiracil as third-line treatment have limited efficacy in metastatic colorectal cancer (mCRC).
METHODS
This Phase 2 trial evaluated the efficacy and safety of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type mCRC patients who achieved clinical benefit with first-line cetuximab-containing therapy. The primary endpoint was 3-month progression-free survival (PFS) rate. A sample size was calculated; 30 patients with a 3-month PFS rate of 45% deemed promising and 15% unacceptable. Patients with greater and less than the cut-off value of cetuximab-free intervals (CFIs) were classified into the long and short CFI groups, respectively, in subgroup analyses.
RESULTS
Among 34 eligible patients who received treatment at least once, 3-month PFS rate was 44.1% (95% confidence interval, 27.4-60.8%). The median PFS and overall survival (OS) were 2.4 and 8.2 months, respectively. The response and disease control rates were 2.9 and 55.9%, respectively. PFS and OS were significantly longer in the long- than in the short CFI group.
CONCLUSIONS
Irinotecan plus cetuximab rechallenge as third-line treatment for KRAS wild-type mCRC was safe and had promising activity, especially in those with a long CFI, warranting further investigation in a Phase 3 randomised trial.
CLINICAL TRIAL REGISTRATION
UMIN000010638.
Identifiants
pubmed: 32863385
doi: 10.1038/s41416-020-01042-w
pii: 10.1038/s41416-020-01042-w
pmc: PMC7652864
doi:
Substances chimiques
KRAS protein, human
0
Irinotecan
7673326042
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Cetuximab
PQX0D8J21J
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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