Phase II study of panitumumab combined with capecitabine and oxaliplatin as first-line treatment in metastatic colorectal cancer patients: clinical results including extended tumor genotyping |
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| Authors: | George Papaxoinis Vassiliki Kotoula Eleni Giannoulatou Georgia-Angeliki Koliou Vasilios Karavasilis Sotirios Lakis Andreas Koureas Mattheos Bobos Elpida Chalaralambous Emily Daskalaki Kyriakos Chatzopoulos George Tsironis Elisavet Pazarli Sofia Chrisafi Epaminontas Samantas Ioannis G. Kaklamanos Ioannis Varthalitis Athina Konstantara Konstantinos N. Syrigos George Pentheroudakis Dimitrios Pectasides George Fountzilas |
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| Affiliation: | 1.Oncology Section, Second Department of Internal Medicine,Hippokration Hospital,Athens,Greece;2.Department of Pathology, Faculty of Medicine, School of Health Sciences,Aristotle University of Thessaloniki,Thessaloniki,Greece;3.Laboratory of Molecular Oncology,Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki,Thessaloniki,Greece;4.Victor Chang Cardiac Research Institute,Darlinghurst,Australia;5.The University of New South Wales,Kensington,Australia;6.Section of Biostatistics,Hellenic Cooperative Oncology Group,Athens,Greece;7.Department of Medical Oncology, Faculty of Medicine, School of Health Sciences, Papageorgiou Hospital,Aristotle University of Thessaloniki,Thessaloniki,Greece;8.Department of Radiology, Aretaieio Hospital,National and Kapodistrian University of Athens,Athens,Greece;9.Department of Clinical Therapeutics, Alexandra Hospital,National and Kapodistrian University of Athens School of Medicine,Athens,Greece;10.Third Department of Medical Oncology,Agii Anargiri Cancer Hospital,Athens,Greece;11.Department of Surgery, School of Health Sciences, General Oncologic Hospital of Kifisia,National and Kapodistrian University of Athens,Athens,Greece;12.Oncology Department,General Hospital of Chania,Crete,Greece;13.Department of Surgery,St. Luke’s Hospital,Thessaloniki,Greece;14.Oncology Unit GPP, Sotiria General Hospital,National and Kapodistrian University of Athens School of Medicine,Athens,Greece;15.Department of Medical Oncology,Ioannina University Hospital,Ioannina,Greece;16.Aristotle University of Thessaloniki,Thessaloniki,Greece |
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| Abstract: | ![]()
This clinical trial assessed the efficacy and toxicity of panitumumab combined with oxaliplatin and capecitabine as first-line treatment in KRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. Patients with exon 2 KRAS wild-type mCRC received panitumumab 9 mg/Kg, oxaliplatin 130 mg/m2, and capecitabine 2000 mg/m2 repeated every 3 weeks. The primary endpoint was objective response rate (ORR, minimum 42 responses). We retrospectively assessed mutations in genes implicated in CRC with massively parallel sequencing; ERBB2 and EGFR amplification with fluorescence in situ hybridization, and tumor-infiltrating lymphocyte density. Among 78 patients enrolled, 45 (57.7%) completed 6 cycles. Most common grade 3–4 toxicities were skin rash (19.2%), diarrhea (18%), and neuropathy (6.4%). Among 5 (6.4%) potentially treatment-related deaths, 2 (2.6%) were characterized toxic. Objective response occurred in 43 (55.1%) of the patients (complete 6.4% and partial response 48.7%; stable 17.9% and progressive disease 7.7%), while 3.8% were non-evaluable and 15% discontinued their treatment early. Additional mutations in KRAS/NRAS/BRAF were found in 11/62 assessable (18%) tumors. After 51 months median follow-up, median progression-free (PFS) was 8.1 and overall survival 20.2 months, independently of KRAS/NRAS/BRAF or PI3K-pathway mutation status. Patients with TP53 mutations (n?=?34; 55%), as well as those with left colon primary tumors (n?=?66; 85%), had significantly better PFS, also confirmed in multivariate analysis. Although the clinical trial met its primary endpoint, according to the current standards, the efficacy and tolerability of the drug combination are considered insufficient. Extended genotyping yielded interesting results regarding the significance of TP53 mutations.ClinicalTrials.gov identifier: NCT01215539, Registration date: Sep 29, 2010. |
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