Afsaneh Barzi, MD, PhD, medical oncologist, director, Employer Strategy (AccessHope), associate professor, Department of Medical Oncology and Therapeutics Research, City of Hope, discusses the combination of regorafenib (Stivarga) and pembrolizumab (Keytruda) in patients with microsatellite stable colorectal cancer.

The combination was evaluated in a phase 1/2 dose escalation study (NCT03657641) with the primary end point of determining the recommended phase 2 dose (RP2D) of regorafenib to be used with a fixed dose of 200 mg pembrolizumab every 3 weeks, Barzi says.

In phase 1, regorafenib was given daily at 80 mg in cohort 1, 120 mg in cohort 2, and 160 mg in cohort 3 on days 1-14 for each 21-day cycle, Barzi explains. After determining the RP2D of 80 mg of regorafenib, phase 2 had the primary end point of progression-free survival, compared with historical data from the phase 3 CORRECT trial (NCT01103323), which evaluated single-agent regorafenib vs placebo, Barzi adds.

After being initiated in June 2019, the phase 1/2 trial completed accrual in July 2021. Of 74 patients enrolled, 73 met the eligibility criteria, with 10 patients treated in phase 1 and 63 treated in phase 2, Barzi concluded.

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Afsaneh Barzi, MD, PhD, discusses the combination of regorafenib and pembrolizumab in patients with microsatellite stable colorectal cancer.


Dr. Barzi on Combination Regorafenib and Pembrolizumab in MSS CRC

Afsaneh Barzi, MD, PhD, medical oncologist, director, Employer Strategy (AccessHope), associate professor, Department of Medical Oncology and Therapeutics Research, City of Hope, discusses the importance of developing novel therapies in metastatic colorectal cancer (mCRC).

Patients with mCRC have several treatment options available, Barzi explains. In the first- and second-line settings, patients typically receive chemotherapy in combination with a biological agent, such as FOLFOX or FOLFIRI in combination with bevacizumab (Avastin). These combinations remain effective strategies for treating patients with metastatic disease, Barzi adds.

In the third- and later-line settings, patients are treated with single-agent regorafenib (Stivarga) or TAS-102 (trifluridine/tipiracil; Lonsurf), Barzi explains. Additionally, data have emerged demonstrating efficacy with the combination of TAS-102 and bevacizumab in this patient population. A small proportion of patients with mCRC harboring 

 fusions can be treated with NTRK inhibitors, Barzi adds.

Ultimately, treatment options for patients with mCRC are limited. Given the prevalence of the disease, which is the third most common cause of cancer-related mortality in the United States, developing novel treatment options is an important area of research for this patient population, Barzi concludes.

Afsaneh Barzi, MD, PhD, discusses the importance of developing novel therapies in metastatic colorectal cancer.



Dr. Barzi on the Importance of Developing Novel Therapies in Metastatic CRC 

Afsaneh Barzi, MD, assistant professor of clinical medicine, Norris Comprehensive Cancer Center, University of Southern California, discusses available and emerging neoadjuvant strategies for the treatment of patients with nonmetastatic pancreatic cancer.

Standard practice used to entail giving patients gemcitabine and evaluating for response. However, the response to gemcitabine is very poor and prevented many patients from going on to surgery, explains Barzi. The LAPACT trial looked at the combination of gemcitabine and nab-paclitaxel (Abraxane). The trial showed that 36% of patients responded to treatment, and about 15% went on to receive surgery.

Moreover, a meta-analysis of FOLFIRINOX studies that were done in patients with locally advanced disease showed that approximately 28% were able to go onto surgery. As chemotherapies become more potent, the chance for resection increases, explains Barzi. Therefore, when patients are staged, they should also be evaluated for resection. Though the majority of patients may not be eligible for surgery, it is worth evaluating for those who are, Barzi concludes.

Dr. Barzi on Available and Emerging Neoadjuvant Approaches in Pancreatic Cancer

Afsaneh Barzi, MD, assistant professor of clinical medicine, USC Norris Comprehensive Cancer Center, discusses surgical advances in the treatment of patients with pancreatic cancer.

Surgery has gotten more aggressive over time, especially when it comes to vascular repair, says Barzi. Surgery as a whole should only be done in high volume centers, adds Barzi. The pylorus preserving Whipple procedure is a relatively new approach to surgery compared with the old standard Whipple procedure. More surgeons are trying to do this in select patients, as it shows better patient tolerability in terms of their diet as well as less gastrointestinal symptoms.

Laparoscopic pancreatectomy is a less invasive surgical approach, adds Barzi, which may help speed up the time of recovery and subsequent adjuvant therapy. Though this procedure is not appropriate for every patient, it can be effective in select populations. Improvements in imaging have also changed how physicians select the patients who are appropriate for surgery, says Barzi.

Afsaneh Barzi, MD

Articles

Dr. Barzi on Combination Regorafenib and Pembrolizumab in MSS CRC

Dr. Barzi on the Importance of Developing Novel Therapies in Metastatic CRC

Dr. Barzi on Available and Emerging Neoadjuvant Approaches in Pancreatic Cancer

Dr. Barzi on Surgical Advances in Pancreatic Cancer