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.
Georgios PapaxoinisVassiliki KotoulaEleni GiannoulatouGeorgia-Angeliki KoliouVasilios KaravasilisSotirios LakisAndreas KoureasMattheos BobosElpida ChalaralambousEmily DaskalakiKyriakos ChatzopoulosGeorge TsironisElisavet PazarliSofia ChrisafiEpaminontas SamantasIoannis G KaklamanosIoannis VarthalitisAthina KonstantaraKonstantinos N SyrigosGeorge PentheroudakisDimitrios PectasidesGeorge FountzilasPublished in: Medical oncology (Northwood, London, England) (2018)
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.
Keyphrases
- wild type
- metastatic colorectal cancer
- phase ii study
- clinical trial
- end stage renal disease
- open label
- ejection fraction
- small cell lung cancer
- newly diagnosed
- chronic kidney disease
- locally advanced
- phase iii
- genome wide
- peritoneal dialysis
- high throughput
- multiple sclerosis
- squamous cell carcinoma
- patient reported outcomes
- study protocol
- metastatic breast cancer
- emergency department
- epidermal growth factor receptor
- radiation therapy
- data analysis
- double blind
- electronic health record
- drug induced
- irritable bowel syndrome