Paul Ruff, MD, director of Medical Oncology at the University of Witwatersrand, Johannesburg, South Africa, discusses the decision regarding the timing of treatment with aflibercept for patients with colorectal cancer.

Some data has shown that if a patient’s chemotherapy backbone is changed but treatment with bevacizumab is continued, good results can be achieved. The decision to stay on bevacizumab or switch to aflibercept depends greatly on an individual patient, Ruff says.

In patients with slowly-progressing disease, it is worth continuing with bevacizumab to achieve the maximum benefit post-progression. In patients with more aggressive progression, it makes sense to switch to aflibercept earlier. Ruff says there is no data that compares the approaches directly.

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Dr. Ruff on the Timing of CRC Treatment With Aflibercept

Paul Ruff, MD, director of Medical Oncology at the University of Witwatersrand, Johannesburg, South Africa, discusses treating elderly patients with colorectal cancer with aflibercept.

Ruff says physicians can use aflibercept to treat elderly patients with colorectal cancer as long as they are careful. Some side effects, such as dehydration, seem to be more severe in patients with colorectal cancer who are over the age of 65, Ruff says.

Ruff believes that most oncologists are aware of how to manage side effects from chemotherapy and anti-angiogenic agents. With good care management and proper awareness of its side effects, aflibercept can be used as a useful agent in the management of advanced colorectal cancer.

Dr. Ruff on Aflibercept in Elderly Patients With CRC

Paul Ruff, MD, director of medical oncology at the University of Witwatersrand, Johannesburg, South Africa, discusses the analysis of prior bevacizumab in the VELOUR trial in patients with metastatic colorectal cancer.

In the trial, about one-third of patients received prior bevacizumab. Bevacizumab is popular in the U.S., Ruff says, and is an anti-angiogenic therapy similar to aflibercept. Though the mechanism of action is different, aflibercept seems to be more potent than bevacizumab in the laboratory, but this has not been proven in the clinic.

In the trial, researchers wanted to see if patients who had received bevacizumab would benefit from aflibercept. Patients did see benefit, Ruff says, as the one-third part of the population who received prior bevacizumab did just as well as those who did not receive bevacizumab.

Dr. Ruff on Prior Bevacizumab in the VELOUR Trial

Paul Ruff, MD, director of Medical Oncology at the University of Witwatersrand, Johannesburg, South Africa, elaborates on factors that can be utilized to select an appropriate antiangiogenic therapy as a second-line treatment in metastatic colorectal cancer (mCRC).

Whether to switch from bevacizumab to aflibercept in the second-line of treatment for patients with mCRC is an important concept that warrants further investigation. This remains particularly clear with recent evidence suggesting that switching the chemotherapy backbone while continuing bevacizumab in the second-line manifests in more efficacious results, Ruff suggests.

The antiangiogenic therapy utilized can be personalized on an individual basis, Ruff notes. As an example, patients who progress slowly on first-line bevacizumab plus chemotherapy are better candidates for continuing this regimen. In this case, aflibercept should be reserved for later lines of treatment. However, for patients with more aggressive, rapidly progressive disease a switch to aflibercept in the second-line may be warranted.Â Â 

While no formal comparison currently exists, Ruff states, aflibercept may be more appropriate for actively progressing patients with mCRC in the second-line setting than bevacizumab.

Paul Ruff, MD, from the University of Witwatersrand, Johannesburg, South Africa, elaborates on factors that can be utilized to select an appropriate antiangiogenic therapy as a second-line treatment in metastatic colorectal cancer.

Dr. Ruff on Selecting Anti- Angiogenic Agents in mCRC

Paul Ruff, MD, director of Medical Oncology at the University of Witwatersrand, Johannesburg, South Africa, discusses a time-course analysis of overall survival (OS) following treatment with ziv-aflibercept (Zaltrap) in patients with metastatic colorectal cancer (mCRC), as observed in the VELOUR trial.

The phase III VELOUR trial examined FOLFIRI alone or in combination with the VEGF-targeted fusion protein aflibercept, following progression on an oxaliplatin-based regimen. The trial included 1226 patients with mCRC and the results were the basis for the FDA approval of aflibercept in early August 2012 (

The median OS for patients receiving the combination was 13.5 months compared to 12.1 for FOLFIRI alone (HR=0.82, 

 = .0032). This is equivalent to an approximate 18% reduction in the risk of dying, Ruff explains.

Furthermore, Ruff adds, the survival advantage with aflibercept appears to be sustained over the course of the trial. At 18 months, aflibercept increased survival by 2.6 months, and by 24 months, survival was prolonged by 4.4 months.

Paul Ruff, MD, from the Witwatersrand, Johannesburg, South Africa, discusses a time-course analysis of overall survival following treatment with ziv-aflibercept in patients with metastatic colorectal cancer, as observed in the VELOUR trial.

Paul Ruff, MD

Articles

Dr. Ruff on the Timing of CRC Treatment With Aflibercept

Dr. Ruff on Aflibercept in Elderly Patients With CRC

Dr. Ruff on Prior Bevacizumab in the VELOUR Trial

Dr. Ruff on Selecting Anti- Angiogenic Agents in mCRC

Dr. Ruff Analyzes Overall Survival in the VELOUR Trial