Transcript Related Guidelines

Right Versus Left-Sided Metastatic Colon Cancer

Benjamin A. Weinberg, MD · Georgetown University

Disclosures

September 02, 2022

Editorial Collaboration

Medscape &

Key Takeaways:

  • The PARADIGM trial demonstrated a statistically significant overall survival benefit in patients with left-sided primary tumors who received panitumumab in the upfront setting with FOLFOX versus those who received bevacizumab with FOLFOX.

  • The results of the PARADIGM trial support the use of anti-EGFR therapy with chemotherapy in the upfront setting of RAS wild-type left-sided metastatic colon cancer.

We've known for a long time that right-sided colon cancer and left-sided colon cancer behave differently and actually respond differently to therapies in the metastatic setting.[1,2,3] The PARADIGM trial out of Japan further supports the usage of anti-EGFR therapy, such as panitumumab, in the upfront left-sided RAS wild-type setting.[4] The PARADIGM trial was a large study of over 800 patients, mostly focused on patients with left-sided primary tumors (ie, rectum, sigmoid, descending colon cancer) and randomized patients 1:1 to receive FOLFOX with panitumumab (anti-EGFR therapy) or FOLFOX with bevacizumab (anti-VEGF therapy). This was a very impressive trial that was focused mostly on the left-sided population. It did include a right-sided population, but the primary endpoint was overall survival on the left-sided population. There was a statistically significant benefit for overall survival in patients who received panitumumab in the upfront setting with FOLFOX as opposed to receiving bevacizumab with FOLFOX with a median overall survival of 37.9 versus 34.3 months and a hazard ratio of 0.82 with a statistically significant P value. If you include the overall population, which included some patients with right-sided tumors, the median survival and hazard ratio were still significant. 

We have known this quite for some time. However, it’s surprising because the progression-free survival—the time to tumor progression—was the same. It was around 13 months in the left-sided group with both arms and around 12 to 13 months in the overall population in both arms.[4] Despite that, the group with panitumumab had a higher response rate, a higher disease control rate, and a longer median duration of response. Importantly, there were actually more patients that got to surgery to resect metastatic disease at a higher rate than the left-sided group that got panitumumab. We’ve been sort of wary of using panitumumab because of the rash side effects,[5] but we should all be aware that there is a survival benefit of using panitumumab in the upfront left-sided RAS wild-type setting. In the right-sided subpopulation, which was only around 187 patients, there was no benefit of panitumumab over bevacizumab, supporting the usage of bevacizumab for patients with right-sided primary tumors. 

This study is impressive but didn’t even account for things like HER2- [or] BRAF-targeted therapies, and those patients probably would not benefit from panitumumab in the upfront setting. There are ongoing molecular studies—biomarker analyses—that will further stratify those groups.[1,2,3] Despite not accounting for those patients, panitumumab was still superior for patients with left-sided RAS wild-type tumors. So, in my clinical practice, based on this study[4] and older studies (such as CALGB 80405),[6] I usually recommend anti-EGFR therapy with chemotherapy in the RAS wild-type left-sided metastatic setting.[7]

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