FOLFOXIRI plus panitumumab vs mFOLFOX6/PAN for unresectable RAS and BRAF wild-type mCC

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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 about the results of the phase III randomised TRIPLETE study into modified FOLFOXIRI plus panitumumab (mFOLFOXIRI/PAN) versus mFOLFOX6/PAN as initial treatment of patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer.

The intensification of the upfront chemotherapy backbone in combination with panitumumab in molecularly selected and mostly (88%) left-sided mCRC patients does not provide any benefit in terms of treatment activity at the price of a non-negligible increase in gastrointestinal toxicity.

The TRIPLETE study is a phase III randomised trial for RAS and BRAF wild-type metastatic colorectal cancer patients. In the TRIPLETE study we basically aimed at verifying whether the intensification of the up-front chemotherapy backbone makes sense when chemo is combined with a targeted agent in a properly selected population. In other words when we use bevacizumab, which is an antiangiogenic agent and has not a targeted population, the intensification of the chemotherapy backbone up front makes a lot of sense, providing a significant advantage in terms of survival. Is this the same when we use anti-EGFR agents, and in particular panitumumab, in molecularly and clinically selected patients?

So we conducted this trial that was an academic trial, no profit, sponsored by the GONO Foundation. More than 50 Italian oncology centres participated in the trial and 435 patients were randomised. The answer to the question is that it does not make sense to intensify the chemotherapy backbone since the primary endpoint of the study, which was the objective response rate, was not met. Patients treated with the triplet of chemotherapy in combination with panitumumab did not experience a higher objective response rate as compared with those treated with the doublet plus the anti-EGFR panitumumab.

Why did we report a negative result? First of all, properly selecting the patients in terms of molecular characterisation – we only enrolled RAS and BRAF wild-type – and those in terms of primary tumour location because most of our patients, 88%, had a left-side primary tumour then we are able to achieve a really interesting result in terms of treatment activity with doublet plus anti-EGFR. So we have already achieved satisfactory results with doublet plus anti-EGFR and the third chemotherapy agent is not able to improve the performance of this regimen that is already well optimised in the right patient population.

The message for clinical practice is it is not recommended to use the triplet in combination with an anti-EGFR because it provides a higher rate of adverse events, in particular of gastrointestinal toxicity. There is not a benefit in terms of treatment activity or progression free survival.