Faculty Opinions recommendation of Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial.

502 Background: Combination chemotherapy of capecitabine plus oxaliplatin (XELOX) with bevacizumab is commonly used as standard chemotherapy for metastatic colorectal cancer (mCRC). A previous meta-analysis showed that there was no difference between two age groups of <65 years and ≥65 years on overall survival (OS) after treatment with chemotherapy with bevacizumab. However, the safety and efficacy of XELOX with bevacizumab in elderly patients (pts) ≥75 years with mCRC remain unclear. Methods: This study was an open-label multicentre phase II study to evaluate the efficacy and safety of XELOX with bevacizumab in pts ≥75 years with metastatic CRC. The primary objective was to assess progression-free survival (PFS). The secondary endpoints were the safety, response rate (RR), time to treatment-failure (TTF) and OS. Results: 36 pts were enrolled. Pts characteristics were; median age 78 (range 75-86); male/female, 21/15; ECOG performance status 0/1, 30/6; colon/rectum 24/12, creatinine clearance (CCr) 60.2 ml/min (range 32.6-84.6). Median follow-up period was 220 days. RR was 55.6% and median TTF was 209 days. The median PFS and median OS are not reached. Grade 3 or 4 adverse events (AEs) were reported in 22 pts (62.8%). Common grade 3 or 4 AEs were hypertension (11.4%), leukopenia (20.0%), peripheral sensory neuropathy (14.3%), hand foot syndrome (8.6%), and fatigue (8.6%). Examining the relationship between renal function (CCr) and AEs, the incidence of Grade 3 or 4 AEs in the lower CCr group was significantly higher than that in the higher CCr group (61.6% vs. 47.8%; p=0.013); hematological toxicities (87.5% vs. 14.8%; p=0.0003) and non-hematological toxicities (61.5% vs. 11.1%; p=0.018). Conclusions: XELOX with bevacizumab is safely administered in elderly patients ≥75 years. Renal function (CCr) could be a good predictive marker for grade 3 or 4 AEs. Clinical trial information: UMIN000003500.

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A phase 3 open-label, randomized, multicenter study of Imprime PGG in combination with cetuximab in patients with KRAS wild type metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.tps787 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. TPS787-TPS787

Author(s):

Richard Dale Huhn ◽

Jamie Lowe ◽

Michele Grady ◽

Corina Candiani Taitt ◽

Michele Anne Gargano ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Trial ◽

Metastatic Colorectal Cancer ◽

Performance Status ◽

Single Agent ◽

Objective Response ◽

The United States ◽

Wild Type ◽

Open Label ◽

Phase 3

TPS787 Background: Imprime PGG (Imprime) is a novel immune modulator (complex carbohydrate biologic), which harnesses innate immune cells to enhance killing of antibody-targeted tumor cells. In a phase 2 single-arm clinical trial in mCRC, the combination of Imprime with cetuximab resulted in 24% ORR, 62% disease control rate (DCR), and median time to progression (TTP) of 12 wks (Tamayo ME, Ann Onc 2010), representing approximate 100% increases vs historical control (Cunningham, NEJM 2004). ORR was 45%, DCR, 82% and TTP, 24 wks in pts with KRAS WT tumors (post hoc analysis). Single-agent cetuximab has been shown to improve objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in patients (pts) with epidermal growth factor receptor (EGFR) expressing, KRAS wild-type (WT) metastatic colorectal cancer (mCRC) who failed oxaliplatin- and irinotecan-based therapy or are intolerant to irinotecan. The mechanism of action of cetuximab is thought to rely on competitive blockade of endogenous ligand binding and downstream signaling, internalization and down regulation of EGFR, as well as antibody-dependent cellular cytotoxicity (ADCC) (Erbitux SmPC). The current trial, sponsored by Biothera (registered with ClinicalTrials.gov NCT01309126) is to confirm these findings in phase 3. Methods: Eligible pts will have had prior oxaliplatin- and irinotecan-based therapy or be intolerant to irinotecan, and will meet key inclusion criteria including measurable disease and ECOG performance status of 0 or 1. In a 2:1 randomization, stratified by geographic region, prior chemotherapy and site, approximately 795 pts will receive weekly open-label Imprime plus cetuximab or cetuximab alone. The primary endpoint of the study is OS and primary analysis will occur when ~709 deaths have occurred. Secondary endpoints include PFS, ORR (based on RECIST 1.1), quality of life, safety and pharmacokinetics. Exploratory endpoints include biomarker analyses. Pt screening and enrollment is underway in the United States and Europe. Clinical trial information: NCT01309126.

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