Meeting
2018 ASCO Annual Meeting
Intensive first line FIr-C/FOx-C association of triplet chemotherapy plus cetuximab in RAS wild-type metastatic colorectal cancer patients: Preliminary phase II data and prediction of individual limiting toxicity syndromes by pharmacogenomic biomarkers.
Authors
Gemma Bruera
Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'aquila, Italy
Gemma Bruera , Silvia Massacese , Francesco Pepe , Umberto Malapelle , Antonella Dal Mas , Eugenio Ciacco , Giuseppe Calvisi , Paolo Marchetti , Giancarlo Troncone , Maurizio Simmaco , Enrico Ricevuto
Organizations
Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'aquila, Italy, Pharmacy Unit, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L'aquila, Italy, Department of Public Health, University Federico II, Napoli, Italy, Pathology, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L'aquila, Italy, S. Andrea Hospital, Sapienza University of Rome, Rome, Italy, Advanced Molecular Diagnostics, S. Andrea Hospital, Rome, Italy
Research Funding
Other
Background: Intensive triplet chemotherapy/bevacizumab significantly increased MCRC outcome. Phase II study investigated safety/activity of FIr-C/FOx-C triplet/cetuximab (CET) in first-line RAS wild-type and prediction of individual limiting toxicity syndromes (LTS) by pharmacogenomic biomarkers. Methods: Simon two-step design: p0 70%, p1 85%, power 80%, α5%, β20%; projected ORR I step 14/19. FIr-C/FOx-C: 5-fluorouracil (5-FU) 12h-timed-flat-infusion 900 mg/m2 d1-2,8-9,15-16,22-23; irinotecan (CPT-11) 160 mg/m2 d1,15, oxaliplatin 80 mg/m2 d8,22; CET 400 then 250 mg/m2 d1,8,15,22; every 28d. Toxicity, individual LTS evaluated, compared by chi-square test; activity/efficacy by log-rank. 5-FU/CPT-11 pharmacogenomic biomarkers, 5-FU degradation rate (5-FUDR), SNPs ABCB1, CYP3A4, DYPD, UGT1A1 evaluated in patients with LTS and at recommended dose. Results: Enrolled: 29 patients < 75 years, primary/intermediate CIRS; from 04/2014 KRAS/NRAS wild-type; median age 59; 7 young-elderly (yE) 24%; 7 liver-limited (L-L) 24%. Recommended CPT-11/5-FU 120/750 mg/m2. Primary endpoint met: OR 14/18 78% as-treated, confirmed in preliminary phase II 17/23 74% intent-to-treat. Liver metastasectomies 14%, 57% L-L. At median follow-up 18 months, PFS 12, OS 23 months. At recommended doses, received DI > 80%; G3-4 toxicities: diarrhea 23%, asthenia 15%, vomiting 8%, hypertransaminasemy 8%; LTS 19 (65.5%), 83% yE. LTS prevalently multiple (ms) vs single site (59 vs 7% p 0.006). Reduced FUDR 56%, SNPs CYP3A4 22%, UGT1A1 71%, > 2 positive pharmacogenomics biomarkers 78% prevalently in patients with gastrointestinal LTS. Conclusions: Intensive first-line FIr-C/FOx-C at recommended doses is tolerable, highly effective in RAS wild-type. Reduced FUDR, CYP3A4, UGT1A1 SNPs may predict individual LTS-ms to select fit patients. Prospective studies personalized by toxicity biomarkers will confirm efficacy. Clinical trial information: Numero EudraCT 2009-016793-32.
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Abstract Details
Session Type
Publication Only
Session Title
Publication Only: Gastrointestinal (Colorectal) Cancer
Track
Gastrointestinal Cancer—Colorectal and Anal
Sub Track
Colorectal Cancer–Advanced Disease
Clinical Trial Registration Number
Numero EudraCT 2009-016793-32
Citation
J Clin Oncol 36, 2018 (suppl; abstr e15517)
DOI
10.1200/JCO.2018.36.15_suppl.e15517
Abstract #
e15517
Abstract Disclosures
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