Third-Line Cetuximab Rechallenge Demonstrates Therapeutic Effectiveness in Metastatic Colorectal Cancer

Erika Martinelli, MD, PhD, University of Campania “Luigi Vanvitelli”, Naples, Italy, discusses findings from a long-term follow-up analysis of the CRICKET and CAVE trials evaluating cetuximab rechallenge in the third-line setting combined with irinotecan or avelumab for patients with RAS wild-type metastatic colorectal cancer.

These findings were presented at the 2022 ESMO World Congress on Gastrointestinal Cancer in Barcelona, Spain.

Transcript:

Good morning. My name is Erika Martinelli. I'm assistant professor at The University of Vanvitelli in Naples. And today I've presented our works that we did in the setting of rechallenge in metastatic colorectal cancer. So basically our work has been done in patient that initially responded to anti-EGFR receptor drug. They progressed and after a period in which anti-EGFR receptor drug is not given, they become again, sensitive to the anti-EGFR receptor blockade.

This was the background of our analysis. We performed an individual patient data pooled analysis of two Italian trial. The CRICKET and the CAVE trial that explored the activity of Cetuximab in combination with both chemotherapy or immunotherapy in the rechallenge setting. These are two Italian trials, so we have the same inclusion criteria for the study. This trial will do in academic fashion and they were temporarily consecutive. So basically our population consisted of 46 patient, 13 from the CRICKET and 33 from the CAVE trial.

And we selected the patient who were RAS/BRAF wild-type at the plasma (ctDNA) analysis. So the major finding of our analysis when we pooled the data was to demonstrate a PFS of 3.9 months in the pooled population and median overall survival of 16.9 months. We also check about the adverse event and we found that a higher percentage of skin rash was reported in the CAVE. So when we use the anti-EGFR receptor plus immunotherapy, and a higher incidence of hematological and non hematological toxicity were reported in the CRICKET trial. But the treatment were tolerated. In fact, the patient were able to receive a subsequent lines of therapy. So basically our analysis demonstrated that rechallenge with Cetuximab, either with [inaudible 00:02:26] or Plus Avelumab is something that is feasible. Of course, we have to select our patient according to the (ctDNA) analysis.

We can only offer rechallenge strategy in patient that are wild-type at the (ctDNA) analysis [inaudible 00:02:44] biopsy. There are some difference of course, in the toxicity according to the treatment that we use. But we can say that, the rechallenge strategy is something that seem to start to prove the activity. Of course, these are retrospective data. It's an individual patient data pooled analysis of two already published studies. So we have to improve this in a larger study. And in fact, we are running two different trial in which we will improve the activity of rechallenge also in a prospective way in cell in patient that are selected according to little biopsy analysis. Thank you.

Source:

Martinelli E, Martini G, Ciardiello D, et al. Evidence of therapeutic effectiveness of third-line cetuximab rechallenge in appropriately selected patients: Findings from long-term follow-up of CRICKET and CAVE trials. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 29-July 2, 2022. Barcelona, Spain. Abstract O-7.