Gastrointestinal cancer experts Dr. Aparna Parikh and Dr. Kristin Ciombor discuss the treatment implications of the phase 3 PARADIGM trial and other advances in colorectal cancer with guest host and ASCO Daily News Associate Editor, Dr. Shaalan Beg.   TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the ASCO Daily News Podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Center and vice president of Oncology at Science 37. I'm delighted to welcome Dr. Aparna Parikh, and Dr. Kristen Ciombor to the podcast today. Dr. Parikh is an assistant professor of Medicine at Harvard University and a GI medical oncologist at the Mass General Hospital Cancer Center. Dr. Ciombor is an associate professor of Medicine and GI medical oncologist at the Vanderbilt University Medical Center. Today, we'll be discussing exciting new approaches using EGFR inhibitors as frontline therapy in colorectal cancer, and promising advances with immune therapy in the treatment of rectal cancer. Our full disclosures are available in the show notes, and disclosures of all guests on the podcast can be found in our transcripts at: asco.org/podcasts. Dr. Parikh, and Dr. Ciombor, it's great to have you on the podcast today. Dr. Aparna Parikh: Thanks so much. Dr. Kristen Ciombor: Thanks so much for having us. Dr. Shaalan Beg: We've seen some exciting advances in GI oncology this year. Let's start with colorectal cancer. Dr. Parikh, there have been many trials looking to compare EGFR and VEGF inhibitors in colorectal cancer. We've heard about the IDEA studies, the FIRE trials, and CALGB 80405. At the 2022 ASCO Annual Meeting, we heard the results of the PARADIGM trial. Have we finally answered the question of when to use EGFR inhibitors as frontline therapy for colorectal cancer? Dr. Aparna Parikh: Thanks so much, Dr. Beg, for this great question. It has been a really exciting year for colorectal cancer across the board. So, the anti-EGFR story is really interesting and has evolved. And maybe just for a little bit of background, we know that colorectal cancer originating from both the right and left side of the colon differ. So, they differ embryologically, and epidemiologically; there are different genetic and molecular aspects to right and left sides of colon cancers. And we have learned over time that in the era of targeted therapy, the primary tumor location has been found to play a very important role, not only in the prognosis of patients but to predict treatment response. We know that patients that have left-sided colon cancers-- and when we think about left-sided colon cancers, we think about cancers that originate from the splenic flexure and descending colon, sigmoid colon, rectosigmoid junction, and sometimes include the rectum in this as well. The rectals have slightly different molecular features than distal colons. And we know that these left-sided patients, overall, have better survival benefits than patients that have right-sided CRC. And that includes again, cecum, ascending colon, hepatic flexure, and transverse colon. So, we know that that had prognostic implications, but what about the predictive implications? And with ASCO, we saw some really exciting data with the PARADIGM study, as Dr. Beg highlighted. We have seen many examples in the past showing the predictive power of anti-EGFR therapy, and anti-EGFR therapy showing a detriment for patients on the right side of the colon. But all these results historically have been obtained by retrospective analysis. So, retrospective analysis of the pivotal CALGB 80405 study, which is the first-line biologic trial. FIRE-3, which is a similar study, but done out of Europe, and KRYSTAL. So all these studies show the same finding but were all obtained basically by retrospective analysis. And what we saw with PARADIGM this year, which is exciting to see, is that this was the first prospective trial to