ASCO 2022 | PARADIGM: Panitumumab plus mFOLFOX6 in RAS wt mCRC
Chiara Cremolini, MD, PhD, University of Pisa, Pisa, Italy, discusses the results of the phase III PARADIGM study (NCT02394795), which assessed panitumumab plus mFOLFOX6 as a first-line therapy in patients with RAS wildtype metastatic colorectal cancer (mCRC). Patients were either given panitumumab or bevacizumab with mFOLFOX6, with overall survival being the primary endpoint. Panitumumab resulted in a superior overall survival, especially in patients with left-sided mCRC. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.
Transcript (edited for clarity)
PARADIGM was a Phase III randomized trial aiming at answering the very important question in the field of RAS white type of metastatic colorectal cancer, which is the best targeted agent to combine with a doublet of chemotherapy in a RAS white type of metastatic colorectal cancer patients. If you see the story of this trial of this protocol, it somehow reacts to the increasing amount of knowledge about the importance of a primary tumor location in identifying those tumors that are really EGFR addicted, and so really may achieve more benefit from an anti EGFR agent, which are tumors originating from the last side of the colon...
PARADIGM was a Phase III randomized trial aiming at answering the very important question in the field of RAS white type of metastatic colorectal cancer, which is the best targeted agent to combine with a doublet of chemotherapy in a RAS white type of metastatic colorectal cancer patients. If you see the story of this trial of this protocol, it somehow reacts to the increasing amount of knowledge about the importance of a primary tumor location in identifying those tumors that are really EGFR addicted, and so really may achieve more benefit from an anti EGFR agent, which are tumors originating from the last side of the colon. In fact, now the primary endpoint of this trial is the overall survival in the left side of the population. So the Paradigm trial answers this question in a prospective way, differently than all of those subgroup, and plan the post hoc analysis analysis of randomized trials that we had available until now.
So really provide a strong evidence of an answer to this question. The answer is that the combination with the panitumumab prolongs the overall survival when compared with the bevacizumab. There is a 3.6 months difference in terms of a median overall survival, and a clear separation of the course in particular at long term. Overall, very good survival results. Very longer durations of overall survival are provided both with doublet plus bevacizumab, and doublet plus panitumumab, in this patient’s population, which is a good prognosis, because these are patients with RAS and BRAF wild type on the left sided primary tumors. On the other side, since the second hierarchical analysis planned by the protocol is the overall survival in the overall population, we do have results also in the right side in the subgroups where results are not such satisfactory, are much more disappointing. This means that both doublet plus panitumumab and doublet plus bevacizumab does not provide impressive results in terms of median overall survival, and we need to find the new solutions for these patients. Nowadays, good results are with the full FOLFOXIRI plus bevacizumab, but the next future probably we will have a more targeted treatments towards actionable or potentially actionable targets.
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