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Cabozantinib/Atezolizumab and the Future of Metastatic Colorectal Cancer Treatment: Thomas Abrams, MD

Thomas Abrams, MD.

Treatment options are limited for patients with metastatic colorectal cancer who have microsatellite-stable disease, which renders them ineligible for immune checkpoint inhibitor therapy. In a cohort of the COSMIC-021 trial, a team of researchers led by Dr. Thomas Abrams, Assistant Professor of Medicine at Harvard Medical School, investigated the efficacy of cabozantinib plus atezolizumab for this patient population. Dr. Abrams recently presented the trial's results at the 2022 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. In this interview, he discusses the role that cabozantinib/atezolizumab may play for patients with metastatic colorectal cancer, particularly those with RAS wild-type disease, in the coming years.  

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today I'm here with Dr. Thomas Abrams, our Editor in Chief. Dr. Abrams, thank you so much for joining us today.

Thomas Abrams, MD: It's my pleasure.

Oncology Data Advisor: So can you give us an overview of the COSMIC-021 trial and the results that your team found?

Dr. Abrams: Sure. This is a very preliminary trial. It's one cohort of a larger multicancer trial looking at a specific pair of drugs. One drug is called cabozantinib, which is a multikinase inhibitor and oral drug that's approved in a number of cancers—not colorectal. The other drug is atezolizumab, which is an immune checkpoint inhibitor also approved in a number of cancers, but not colorectal cancer. The colorectal cohort was a 30-patient cohort in which all the patients had microsatellite-stable disease, so ordinarily not candidates for immune checkpoint inhibitor treatment. That comprises roughly 95% of the metastatic colorectal cancers that are out there. It's the much more common variety. Since we don't have immune checkpoint inhibitors available for the vast majority of patients, this is the kind of trial that's very important, because we want to figure out ways to utilize immune therapy for these patients. It's a huge unmet need in the treatment of advanced colorectal cancer.

We had these 30 patients with microsatellite-stable disease who had already received at least one prior treatment for advanced disease. Most of the patients had received two prior treatments. It was a pretty heavily pretreated population. They were enrolled on the trial and started receiving this combination of the oral drug, cabozantinib, and the intravenous (IV) drug atezolizumab, and each cycle was three weeks. The atezolizumab was delivered once every three weeks, and the cabozantinib was a daily drug that was taken at home.

It's a descriptive study. The primary end point is overall response rate. Then there are secondary end points of duration of response, progression-free survival, and overall survival, as well as safety. In this trial, three patients had responses by Response Evaluation Criteria in Solid Tumors (RECIST), meaning they had 30% reduction in the size of their tumor. Then an additional quarter of the patients had disease control, and the rest progressed. But that's pretty good. When you look deeper into the numbers, you see that the benefits accrued primarily in patients who had a wild-type RAS gene—RAS is a gene that is very important in colorectal cancer. It's mutated about 60% of the time, and patients who have a mutated RAS gene are ineligible for epidermal growth factor receptor (EGFR) inhibitors, so they're at a disadvantage. In this trial, which is very preliminary, the benefit accrued to the other population, the patients who had no mutation in the RAS gene. That's a really interesting observation, and it may provide the basis for future research.

I don't think that this trial is going to have immediate implications for treatment. We're not going to be using this combination for patients with advanced colorectal cancer until a lot more research is done. But when we design the next step, we're going to look and think that maybe we want to enrich our population with RAS wild type or even limit it to RAS wild-type populations, because the combination really seemed to do better in that group. That can also jumpstart a lot of investigations for primary research, for early-phase research, and for looking at the reasons for why that might be the case. I think it's a really interesting combination. The safety was what you'd expect, so that's an important thing. It wasn't highly toxic, and there were no treatment-related deaths. Patients seemed to do fairly well on it. I think it's ultimately a promising combination, but much more research is needed before it becomes an accepted treatment in the armamentarium.

Oncology Data Advisor: Well, thank you for sharing this research with us.

Dr. Abrams: My pleasure.

About Dr. Abrams

Thomas Abrams, MD, is an Assistant Professor of Medicine at Harvard Medical School, a Senior Physician at Dana-Farber Cancer Institute, and the Director of the Liver Cancer Task Force of the Harvard Cancer Center. He also serves as the Editor in Chief of Oncology Data Advisor. Dr. Abrams specializes in the treatment of patients with gastrointestinal cancers, including pancreatic, gastric, colorectal, esophageal, gallbladder, and primary liver cancers. His research interests include the early detection of liver cancers through the discovery and application of novel biomarkers. He has authored or coauthored numerous publications in peer-reviewed journals.

For More Information

Abrams TA, Kazmi SMA, Winer IS, et al (2021). A phase 1b multitumor cohort study of cabozantinib plus atezolizumab in advanced solid tumors (COSMIC-021): results of the colorectal cancer cohort [oral presentation]. Presented at: 2022 ASCO Gastrointestinal Cancers Symposium. Abstract 121. DOI:10.1200/JCO.2022.40.4_suppl.121

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor. 


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