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FDA approves Stivarga to treat metastatic colorectal cancer
The FDA approved regorafenib, a multikinase inhibitor, for use in patients with metastatic colorectal cancer that progressed after prior treatment.
The agency approved regorafenib (Stivarga, Bayer HealthCare Pharmaceuticals) under its priority review program. Approval came a month ahead of the scheduled review completion date of Oct. 27.
“Stivarga is the latest colorectal cancer treatment to demonstrate an ability to extend patients’ lives,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “[It] is the second drug approved for patients with colorectal cancer in the past 2 months.”
The FDA in August approved ziv-aflibercept (Zaltrap, Sanofi-Aventis) for treatment of metastatic colorectal cancer in combination with FOLFIRI chemotherapy.
The FDA based its approval of regorafenib on results of a randomized study that involved 760 patients.
The researchers assigned participants to regorafenib or placebo in addition to best supportive care. Treatment continued until their disease progressed or side effects became unmanageable.
Participants assigned to regorafenib demonstrated longer median OS (6.4 months vs. 5 months) and longer median PFS (2 months vs. 1.7 months) than those assigned to placebo, according to study results.
Upon release, the drug will include a boxed warning alerting patients and physicians that fatal liver toxicity occurred in some study participants treated with regorafenib.
The most common side effects reported in patients treated with the drug include fatigue, loss of appetite, hand-foot syndrome, diarrhea, mouth sores, infection, high blood pressure and dysphonia.
Perspective
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We anticipated the approval of regorafenib (Stivarga, Bayer) by the FDA without concerns. The study has been in the public eye for a few months, including a recent presentation at ASCO. This is now the second approval in the last two months for advanced colorectal cancer. In August, the FDA approved ziv-aflibercept (Zaltrap, Sanofi-Aventis) for use in combination with folinic acid, fluorouracil and irinotecan (FOLFIRI) chemotherapy in patients with colorectal cancer.
The interesting thing about regorafenib is that, unlike all other approved biologic agents for colorectal cancer, this is the first oral targeted treatment approved by the FDA. The other interesting finding about this agent is that, unlike other vascular endothelial growth factor (VEGF) inhibitors, it has single-agent activity in colorectal cancer. This is probably explained by the fact that it is a multikinase inhibitor targeting VEGF and numerous other targets on the cancer cell and its microenvironment.
Overall, the approval of regorafenib continues to help expand the therapeutic arsenal in colorectal cancer. However, I think it is crucial for us to find a biomarker to better select patients who will respond to regorafenib given its potential cost and toxicities.
Perspective
Back to TopRegorafenib (Stivarga, Bayer) is an oral, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor that also targets other tyrosine kinases, including RAF. It is the first VEGF-targeted agent to improve survival in metastatic colorectal cancer as a single agent. The CORRECT trial, which compared regorafenib with placebo, was conducted essentially in patients who have failed all chemotherapies and had no treatment options. The agent opens up a new avenue of treatment for patients with refractory colorectal cancer. In conjunction with recent data, the data for regorafenib suggest that continued suppression of VEGF pathways into multiple lines of therapy conveys a survival benefit in patients with colorectal cancer.
The VELOUR trial, which validated survival benefit for the VEGF ligand trapping agent aflibercept (Zaltrap, Sanofi-Aventis), and the TML trial, which indicated survival benefits for continuation of bevacizumab (Avastin, Genentech) into second-line therapy beyond progression on first-line therapy, underscore this theme. There is going to be a lot of interest in looking at regorafenib in earlier lines of therapy either as a single-agent or in combination with other chemotherapy regimens. I think it will stimulate interest in studying this drug in other gastrointestinal cancers, as well. It is a very exciting development and a significant advance.