Reviewing the Metastatic Colorectal Cancer Treatment Algorithm
Key Points
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Treatment options are limited for patients with metastatic colorectal cancer who progress on upfront chemotherapy.
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Approved second-line options include trifluridine-tipiracil (TAS-102) plus bevacizumab, regorafenib, and fruquintinib.
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The STELLAR-303 trial found that zanzalintinib plus atezolizumab showed a small efficacy benefit compared with regorafenib but had a limiting side-effect profile, with a high rate of grade 3 adverse events.
Treatment Options for Refractory Metastatic Colorectal Cancer
Cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, discussed key takeaways from two moderated discussions that reviewed the current standard of care treatment for patients with refractory metastatic colorectal cancer.
During a discussion with John Strickler, MD, of Duke University, and Chiara Cremolini, MD, PhD, of the University of Pisa, the doctors emphasized the importance of upfront next-generation sequencing (NGS) and biomarker testing to guide targeted recommendations for first-line treatment. The discussion then addressed available second-line options in the absence of actionable mutations. Approved options in the second line include TAS-102 plus bevacizumab based on the SUNLIGHT trial, regorafenib based on the CORRECT trial, and fruquintinib based on the FRESCO-2 trial.
In the SUNLIGHT trial, TAS-102 was dosed at 35 mg/m2 on days 1 through 5 and 8 through 12 of each 28-day cycle. However, in clinical practice, dosing has largely been switched to days 1 through 5 and 15 through 19 to improve tolerability, said Dr. Rohit Gosain. Regorafenib also received updated dosing guidance based on the reDOS study. Initially, regorafenib was approved at a dose of 160 mg daily for 3 weeks followed by 1 week off. The reDOS study showed improved tolerability with a step-up schedule of 80 mg daily for 1 week, then 120 mg daily for 1 week, then 160 mg daily for 1 week, followed by the standard schedule of 160 mg daily for 3 weeks, then 1 week off. For fruquintinib, the consensus has been to start all patients at 5 mg daily for 3 weeks, followed by 1 week off, and then reduce the dose if the patient is experiencing difficult toxicity.
Toxicities to monitor for include rash, fatigue, and thyroid dysfunction with fruquinitinb; neutropenia, hypertension, and poor wound healing with TAS-102 plus bevacizumab; and diarrhea, fatigue, rash, and hand-foot syndrome with regorafenib.
STELLAR-303 and Second-Line Sequencing
Drs. Rahul and Rohit Gosain also reviewed their second discussion with Neena Vijayvergia, MD, of Fox Chase Cancer Center, and Tiago Biachi, MD, PhD, of Moffitt Cancer Center. This talk discussed the sequencing of the approved second-line options after upfront chemotherapy is exhausted. In general, it’s common practice to sequence TAS-102 plus bevacizumab, then regorafenib, and then fruquintinib or potentially clinical trials, said Dr. Rahul Gosain. The oncologists stressed that treatment in this setting has palliative intent, so treatment decisions should prioritize quality of life.
This discussion also reviewed the phase 3 STELLAR-303 study on zanzalintinib plus atezolizumab versus regorafenib in refractory metastatic colorectal cancer. The data showed that zanzalintinib plus atezolizumab had a “modest” benefit but a concerning side effect profile compared with regorafenib, said Dr. Rohit Gosain.
Overall, Drs. Rahul and Rohit Gosain highlighted the need for NGS testing in refractory metastatic colorectal cancer, but generally noted that treatments for this population are limited and there is an unmet need for better options.