The Role of CTLA-4 Inhibition in Immunotherapy for MSI-H/dMMR Metastatic Colorectal Cancer

H&O When is immunotherapy used in microsatellite instability–high/mismatch repair–deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC)? CW Immunotherapy is used for patients with mCRC whose tumors test positive […]

EGFR Inhibitor Rechallenge in Metastatic Colorectal Cancer

H&O How often do patients with colorectal cancer (CRC) develop metastatic disease? JG Most CRC patients present with stage 1, 2, or 3 disease, with only […]

The Role of Antiangiogenesis Agents in Refractory Metastatic Colorectal Cancer

H&O What are the standard treatment options for patients with refractory metastatic colorectal cancer (CRC)? SK Patients with refractory metastatic CRC typically have already received chemotherapy […]

Factors Guiding Selection of Treatment in Metastatic Colorectal Cancer

H&O What factors guide selection of treatment in metastatic colorectal cancer? LS Metastatic colorectal cancer is a very broad area that requires an individualized approach to […]

Hem/Onc News

Clinical Advances in Hematology & Oncology Volume 14, Issue 11, November 2016 Devon Schuyler Daratumumab Improves Progression-Free Survival in Relapsed/Refractory Myeloma The addition of daratumumab (Darzalex, […]

Phase II Trial of FOLFOX6, Bevacizumab, and Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer

Abstract: Purpose: To examine FOLFOX/bevacizumab/cetuximab in the first-line treatment of metastatic colorectal cancer (mCRC). Methods: Design: Randomized phase II trial aimed at achieving a 60% objective response rate (ORR). Due to frequent cetuximab-related hypersensitivity reactions the trial was amended to a single-arm design. Eligibility: Previously untreated mCRC, measurable disease, Eastern Cooperative Oncology Group performance status (ECOG-PS) 0–1. Treatment: Modified FOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 350 mg, and 5-fluorouracil 400 mg/m2 bolus; 2.4 g/m2 infusion, 46 h) day 1; bevacizumab 5 mg/kg on day 1; cetuximab 400 mg/m2 on day 1, then 250 mg/m2 on days 1 and 8, every 14 days (1 cycle) until progressive disease (PD); restaging occurred every 4 cycles. Results: With emerging negative progression-free survival (PFS) data from a similarly designed trial, this trial closed early. Enrollment (N=31) was from August 2005–June 2008. Patient characteristics: Median age was 55 years (29–78); 58% were male; 71% were ECOG-PS 0. Ten cycles (median) were completed (range 2–62). The ORR was 55% (95% confidence interval [CI], 36–73%); 11 patients (35%) had stable disease; 1 patient (3%) had PD; 2 patients (6%) were unevaluable. Median PFS was 9 months (95% CI, 8.3–15.2 months); median overall survival was 25.7 months (95% CI, 15.4–27.6 months). Grade 3/4 toxicities (>1 patient) included neutropenia (25%), rash (23%; grade 2 events, 45%), diarrhea (19%), fatigue (16%), pain (16%), anemia (13%), sensory neuropathy (13%), deep-vein thrombosis (10%), nausea (10%), pulmonary embolism (7%), anorexia (6%), and vomiting (6%). Conclusion: In this limited trial, it is unclear whether cetuximab contributed to FOLFOX/bevacizumab efficacy, although the response rate, PFS, and overall survival were high. The regimen was generally well-tolerated, with expected skin effects; thromboembolic rates should be assessed in larger analyses. Cetuximab’s role in first-line mCRC treatment is likely best guided by K-RAS testing in future clinical trials.

BRAF Testing in Advanced Colorectal Cancer: Is It Ready for Prime Time?

Abstract: iven that KRAS mutant colorectal tumors do not respond to anti-EGFR monoclonal antibodies such as cetuximab or panitumumab, it is now standard that all patients with metastatic colorectal cancer who are candidates for these therapies undergo KRAS testing. BRAF encodes a protein kinase, which is involved in intracellular signaling and cell growth and is a principal downstream effector of KRAS. BRAF is now increasingly being investigated in metastatic colorectal carcinoma. BRAF mutations occur in less than 10–15% of tumors and appear to be poor prognostic markers. However the predictive nature of this biomarker is yet undefined. This article will review the evidence behind both KRAS and BRAF testing in metastatic colorectal cancer.