ASCO 2014: Chemotherapy Plus Either Bevacizumab or Cetuximab Results in Similar Survival Benefits in Metastatic Colorectal Cancer

Key Points

  • Bevacizumab plus chemotherapy and cetuximab plus chemotherapy produced equal survival benefits for patients with metastatic colorectal cancer and no KRAS mutations.
  • Overall survival was 29 months in the bevacizumab-plus-chemotherapy group vs 29.9 months in the cetuximab-plus-chemotherapy group.
  • Progression-free survival was 10.8 months in the bevacizumab-plus-chemotherapy group vs 10.4 months in the cetuximab-plus-chemotherapy group.

Bevacizumab (Avastin) plus chemotherapy and cetuximab (Erbitux) plus chemotherapy produced equal survival benefits for patients with metastatic colorectal cancer and no KRAS mutations, according to results from a large federally funded phase III study presented at the 2014 ASCO Annual Meeting (Abstract LBA3).

There were no significant differences in either overall or progression-free survival between the treatment groups. Overall survival was 29 months in the bevacizumab-plus-chemotherapy group vs 29.9 months in the cetuximab-plus-chemotherapy group. Corresponding progression-free survival was 10.8 months vs 10.4 months. The data also suggest that either FOLFOX (oxaliplatin, fluorouracil [5-FU], and leucovorin) or FOLFIRI (irinotecan, 5-FU, and leucovorin) chemotherapy regimens are acceptable in combination with either bevacizumab or cetuximab.  

Chemotherapy Was Predominantly FOLFOX

“About 75% of patients with metastatic colorectal cancer in the United States initially receive bevacizumab-based therapy, although we know that cetuximab-based therapy is also a good option for a subset of patients,” said lead author Alan P. Venook, MD, the Madden Family Distinguished Professor of Medical Oncology and Translational Research at the University of California, San Francisco. “Our findings clearly show that the two antibodies—with either FOLFOX or FOLFIRI—are both acceptable, and similarly effective. This should reassure doctors and patients facing decisions about treatment selection.”

Targeted therapies have played a key part in extending survival for patients with metastatic colorectal cancer. Bevacizumab targets vascular endothelial growth factor (VEGF), whereas cetuximab targets epidermal growth factor receptor (EGFR). Bevacizumab with FOLFOX is widely used in the United States, while cetuximab-based regimens tend to be used more frequently in Europe, according to ASCO.

In the current study, 1,137 patients with untreated KRAS wild-type tumors (codon 12 and 13) metastatic colorectal cancer were randomly assigned to receive bevacizumab plus chemotherapy or cetuximab plus chemotherapy. The selection of chemotherapy was based on physician preference, and 73.4% of patients received FOLFOX vs 26.6% getting FOLFIRI. “The preference for FOLFOX limits chemotherapy comparison,” the authors noted.

The median age of patients was 59, and 61% were male. The median follow-up was 24 months.

No New Side Effects

No new treatment side effects were detected in the study. Common adverse events of bevacizumab are high blood pressure, headache, mouth sores, nosebleed, diarrhea, rectal bleeding, loss of appetite, fatigue, and weakness. The most common side effects of cetuximab are acne-like rash, itching, changes in fingernails and toenails, infections, fatigue, and low blood electrolyte levels.

FOLFIRI and FOLFOX also differ in side effects. FOLIFIRI causes more hair loss and diarrhea, but FOLFOX causes neuropathy that often necessitates stopping treatment.

“When two arms of a study show equal survival, quality of life takes on new meaning,” Dr. Venook said at the 2014 ASCO Annual Meeting Plenary Session. Updated analyses reflected differences in the toxicities of the agents, but show that the overall quality of life for patients on either of the antibodies is similar.

New Benchmark Applies in a Variety of Settings

“The conclusion was there is no difference between these two therapies as the starting point for patients. Patients came off of this designated treatment and 88% went on to subsequent different treatments and at the end of the day, the survival was the same,” Dr. Venook stated at the ASCO plenary press briefing. “What this tells us is that either FOLFIRI or FOLFOX with either bevacizumab or cetuximab are perfectly reasonable options for first-line therapy for this population of patients. Essentially, patients and doctors have four choices…of which therapy they might initiate. Patients can make this decision based on preference for toxicities and other issues because these treatments appear to be equivalent in terms of long-term outcome.”

“The other meaningful difference,” Dr. Venook added, “is that the overall survival exceeding 29 months in both arms really establishes a new benchmark for patients with colorectal cancer. This was accomplished through a broad clinical network through the United States and Canada and suggests that the results apply in a variety of practice settings, not just in academic settings.” He noted that about 10% of the patients in the study are living beyond 5 years with advanced metastatic colorectal cancer.

Value of Publicly Funded Research

The results of the study point out the value of publicly funded research, Dr. Venook remarked. “This is a study that clarifies the standard of care, that answers a question that industry might not ask,” he said. “This is incredibly important to practicing oncologists who face this question every day. These drugs are readily accessible in the United States and Canada and around the world.”

Future analyses from this study will focus on different subsets of patients and include detailed molecular analyses, which “we hope … will inform future studies in colorectal cancer,” Dr. Venook said. “What I present today is really the tip of the iceberg in terms of what we stand to learn from this study.”

This research was supported in part by the National Cancer Institute, National Institutes of Health; Imclone; Roche; Genentech; Bristol-Myers Squibb; and Eli Lilly. Dr. Venook reported a consultant or advisory role with and research funding from Bristol-Myers Squibb and Roche/Genentech. For full disclosures of the study authors, view the study abstract at

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.