Data from the PARADIGM trial that were presented at 2022 ASCO demonstrated that panitumumab plus FOLFOX should be standard of care for patients with left-sided, RAS wild-type colorectal cancer, according to Tanios S. Bekaii-Saab, MD.
When asked by CancerNetwork® about the most important data to come out of the 2022 American Society of Clinical Oncology Annual Meeting, Tanios S. Bekaii-Saab, MD, Gastrointestinal Cancer Program lead at the Mayo Clinic Cancer Center and medical director of the Cancer Clinical Research Office as well as vice chair and section chief for Medical Oncology in the Department of Internal Medicine at the Mayo Clinic in Phoenix, Arizona, detailed how data from the phase 3 PARADIGM trial (NCT02394795) examining panitumumab (Vectibix) plus folinic acid, fluorouracil, and oxaliplatin (FOLFOX) vs bevacizumab (Avastin) plus FOLFOX may change the standard of care for certain patients with colorectal cancer.1 In patients with RAS wild-type, left-sided tumors, panitumumab/FOLFOX induced better survival outcomes vs bevacizumab/FOLFOX in the frontline setting.
At ASCO, the data that were presented that are most interesting in terms of consolidating our standard of practice were from the PARADIGM trial that was presented by Takayuki Yoshino, MD, from Japan. The study included both left-sided and right-sided tumors, but it was powered to determine if the left-sided tumors seem to benefit more from panitumumab plus FOLFOX vs bevacizumab plus FOLFOX and look at the survival of the overall population, and if that’s positive it could establish a new standard.
To make it simple, the study was positive, indicating that FOLFOX and panitumumab should be considered as a standard first-line option for most patients with RAS wild-type, left-sided tumors. Although this was not presented, those patients should have BRAF wild-type and HER2-nonamplified tumors as well to qualify for panitumumab. That accounts for about 20% to 25% of the patients with colon cancer. Whether you would favor FOLFOX/panitumumab over FOLFOX/bevacizumab, we always knew that there were these hints that EGFR inhibitors may play a better role than VEGF inhibitors in the first line. For left-sided tumors that are RAS wild type, this is still the first prospectively randomized and designed study that actually answered this question.
There are certainly questions that remain. What do you do with patients for whom FOLFOXIRI [FOLFOX plus irinotecan] plus bevacizumab is a better option? This trial doesn’t address that, and that accounts for quite a few patients in my practice, [such as] the younger ones or the more performant ones for whom I still prefer to go with a 3-month exposure of FOLFOXIRI plus bevacizumab followed by capecitabine plus bevacizumab maintenance where you get less likelihood of high-level toxicities that are cumulative. The good news is that there were some hints that you may not need to continue chemotherapy or the EGFR inhibitor. You can employ a strategy where you treat patients for few months and then you stop therapy. That may resolve the concern relating to cumulative toxicity coming from EGFR inhibitors.
There have also been some data from the PANAMA trial [NCT01991873] that looked at a maintenance strategy with an EGFR inhibitor.2 There are mitigating elements with concern to EGFR inhibitors being used continuously for which you could essentially apply strategies [such as] either stopping them or just maintaining the biologic, so that may mitigate some of these concerns. There are other concerns as well, but PARADIGM establishes the fact that FOLFOX plus panitumumab should be the standard for patients with RAS wild-type tumors that are on the left side, as well as BRAF and HER nonamplified.