Quality of life, compliance, safety and effectiveness in fit older metastatic colorectal patients with cancer treated in first-line with chemotherapy plus cetuximab: A restrospective analysis from the ObservEr study.

OBJECTIVES: The influence of age (<70 years and ≥70 years) was retrospectively studied on the quality of life (QoL), incidence of side effects (including skin reactions) and efficacy of chemotherapy plus cetuximab in patients with KRAS wild type (WT) metastatic colorectal cancer (mCRC). METHODS: 225 patients of the Observed study (PS 0-1) were retrieved based on age (< 70 and ≥70 years) and evaluated through EORTC QLQ-C30 and DLQI questionnaires. RESULTS: The two patient groups (141 < 70 and 84 ≥ 70 years, respectively) were balanced with no differences in any of the clinical and pathological characteristics considered. Both groups underwent similar type of first-line chemotherapy plus cetuximab, treatment duration and compliance. Cetuximab therapy caused similar incidence of side effects and impact on QoL in older and younger patients. No difference was observed in progression free survival (PFS) and in disease control rates between the two patient populations. Median overall survival (OS) was higher in patients <70 (27 months, 95% CI: 22.7-31.27) than in patients ≥70 (19 months, 95% CI: 14.65-23.35) (p = 0.002), which is likely due to higher proportions of metastatic resection (27.0% vs 8.3%; p = 0.001) and utilization of second-line therapy in younger group (58.9% vs 42.9%; p = 0.028). CONCLUSION: The current data suggest that fit older patients with mCRC can be safely treated with a cetuximab-based therapy, as QoL and safety profile do not seem to be affected by age. In addition, age did not impact the choice of chemotherapy to be associated to cetuximab and treatment compliance.

Heterogeneity in the colorectal primary tumor and the synchronous resected liver metastases prior to and after treatment with an anti-EGFR monoclonal antibody.

Molecular heterogeneity between primary tumors (PTs) and synchronous resected liver metastasis in colorectal cancer (CRC) has potential relevance in treatment strategies. Next-generation sequencing (NGS) may be able to increase the chances of identifying multiple molecular driver alterations, calling for therapy. The aim of the present study was to evaluate mutations in PT and synchronous resected liver metastases for patients with Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) exon 2 wild-type metastatic (m)CRC who underwent chemotherapy (CT) featuring an anti-epidermal growth factor receptor (EGFR) monoclonal antibody. Genomic analysis was performed on 54 lesions from 7 patients with mCRC. For each patient, a PT biopsy or a surgical specimen was obtained prior to CT, and the PT and all liver metastases resected following CT were analyzed. DNA libraries were generated using the Ion AmpliSeq Colon and Lung Cancer Panel, assessing the most frequent somatic mutations in 22 genes involved in colon tumorigenesis, and sequencing was performed on an Ion Personal Genome Machine system. A partial response was achieved in all the patients, with a median progression free survival time of 11 months (range, 3-21 months). All the patients were subjected to surgical liver metastasis resection. The median overall survival time was 31 months (range, 4-46 months). Molecular analysis of the genes correlated with the target therapy, suggesting significant intratumor heterogeneity, as revealed by the different mutational landscape of certain PTs and synchronous resected liver metastases following systemic therapy when compared with the PT prior to treatment. In particular, the loss and acquisition of mutations in KRAS, neuroblastoma RAS viral oncogene homolog (NRAS), tumor protein p53 (TP53), the p110α catalytic subunit of phosphoinositide 3-kinase (PIK3CA), F-box/WD repeat-containing protein 7 (FBXW7) and phosphatase and tensin homolog (PTEN) were observed. In addition, one patient developed a mucinous pattern following systemic CT. Taken together, the results of the present study demonstrated that intratumor heterogeneity is likely to affect the response to therapy, and to drive acquired resistance to targeted agents. The preliminary data also suggest a potential role for NGS in the evaluation of biological drug resistance, affecting future sequential treatment strategies.

Long-term survival in an advanced gastric cancer patient treated with cetuximab in association with FOLFIRI: a case report.

In December 2004, a 52-year-old woman with metastatic gastric cancer was enrolled in the phase II clinical trial FOLCETUX, receiving cetuximab at an initial dose of 400 mg/m(2) i.v. followed by weekly doses of 250 mg/m(2), irinotecan 180 mg/m(2) i.v. on day 1, LFA 100 mg/m(2) i.v. followed by 5-FU 400 mg/m(2) i.v. bolus and 600 mg/m(2) i.v. 22-h continuous infusion on days 1 and 2 every two weeks, to a total of 17 cycles. CT and PET-CT performed after six weeks treatment failed to show any residual disease, with complete radiological response in accord to RECIST criteria and complete metabolic response. A total of 24 maintenance administrations with cetuximab alone (250 mg/m(2) weekly) were performed, as foreseen by the protocol in responders. In November 2012 a clinical, radiological (CT) and metabolic (PET-CT) patient examination proved negative for recurrent disease, signifying 95 months' progression free survival.

Bevacizumab plus chemotherapy in metastatic colorectal cancer patients treated in clinical practice.

AIM: The effect of KRAS status on response to bevacizumab plus chemotherapy in metastatic colorectal cancer is still unclear. We aimed to evaluate the overall clinical response to such a therapy in clinical practice and assess the role of KRAS status on therapy response. PATIENTS & METHODS: This was a retrospective study enrolling 108 metastatic colorectal cancer patients. KRAS mutation analysis was performed by PCR. RESULTS: Overall, 41.7% of patients had stable disease, 39.8% a partial response, 3.7% a complete response and 14.8% disease progression. Both clinical benefit and objective response rate tended to be higher in patients with only hepatic metastases than those with extrahepatic or multiple metastases. Response to therapy would appear to be independent of KRAS status, but larger studies are needed. CONCLUSION: Bevacizumab plus chemotherapy provides clinical benefit and objective response rate in patients with metastatic colorectal cancer independently of KRAS expression, especially in those patients with only liver metastases.