Comment: Panitumumab plus mFOLFOX6 improves OS for RAS wild-type left sided mCRC

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Published: 6 Jun 2022
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Dr Chiara Cremolini - University of Pisa, Pisa, Italy

Dr Chiara Cremolini speaks to ecancer at ASCO 2022 in Chicago commenting on the results from the phase 3 PARADIGM trial


The trial endeavours the first-line treatment in patients with RAS wild-type (WT) metastatic colorectal cancer and the response to the treatment.

Dr Cremolini discusses the interesting distinctions in the results of panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6.

Watch our video on this study here

Read our news article here

Watch the press conference on this study here

PARADIGM is a randomised trial that was conducted in Japan in almost 200 centres in Japan. It aims at improving the upfront treatment of patients with metastatic colorectal cancer and, in particular, of RAS wild-type metastatic colorectal cancer patients. In the last years three head-to-head randomised trials were conducted to address this question which is which is the best targeted agent to be combined with a doublet of chemotherapy in RAS wild-type metastatic colorectal cancer patients? Unfortunately, those trials failed to provide a conclusive answer to this question. 

A few years later we understood that the primary tumour location matters, not only in terms of prognosis but also in terms of prediction. Because in left-sided RAS wild-type patients we observe a clear advantage from using anti-EGFR based regimens instead of bevacizumab but this is not the case for patients with RAS wild-type tumours originating from the right side of the colon.

These results were provided by the subgroup analysis, unplanned and post-hoc subgroup analysis, of these randomised trials. Now we have PARADIGM which is a prospective trial with the primary endpoint of overall survival in the left-sided population. So the final objective is to verify whether anti-EGFR based regimens provide a survival benefit when compared with bevacizumab-based regimens in left-sided RAS wild-type metastatic colorectal cancer patients. And the answer is yes because actually there is an overall survival advantage. These patients experience overall very long durations of median overall survival which is good news, in particular, over 35 months in both arms. So the landmark of 30 months for RAS wild-type patients is no longer there – we can do better.

We can do better in left-sided patients, RAS wild-type, treated with anti-EGFR based up-front regimens. Clearly the benefit is not the same in the overall RAS wild-type left-sided population because the shape of the curves shows a clear overlap for the first 28 months of observation but then there is this clear separation and the long-term benefit from the use of anti-EGFR agents.

Overall the results of the PARADIGM trial strengthen the choice of using in left-sided RAS wild-type metastatic colorectal cancer patients anti-EGFR based regimens.