The VOLFI trial is a phase II trial with nearly 100 patients included, so just a smaller trial. However, it has a very important message because it’s the first trial so far randomising the triplet, FOLFOXIRI, a very active chemotherapy in metastatic colorectal cancer against the triplet plus any monoclonal antibody. So far in every arm in the randomised trials bevacizumab was included and therefore this is the first, in principle, questioning if a monoclonal antibody could add anything on to FOLFOXIRI.
It was a phase II randomised trial in ECOG 0-1 patients, RAS wildtype, very important. We had pre-specified two cohorts, cohort one were patients judged at the original tumour boards by the surgeons as definitely unresectable and the cohort two were the patients with a chance of a secondary resection. I think this is very important for the results. The primary endpoint, objective response rate, was met so we had an increase from 66% with FOLFOXIRI to 86.7% with the FOLFOXIRI plus panitumumab, so a significant increase. We saw the same gain in response rates also in left-sided as well as in right-sided disease and also with small numbers, 16 patients, in BRAF mutated disease. This was somehow surprising but this was an important message, the first finding.
The second finding – there was a significant increase in secondary resections. In the cohort two with a chance of secondary resection there was a 75% resection rate with panitumumab, so three out of four, compared to FOLFOXIRI just 34%. So this was a huge gain for the patients. The PFS was equal which we would somehow expect because the EGFR antibodies in former trials did not increase PFS. But we saw a very good trend in overall survival with a hazard ratio of below 0.7 in favour of panitumumab. If we just look to the cohort two patients we saw an increase in median overall survival from around 41 months to 52 months, so nearly one year longer overall survival in patients resected when they were treated in the conversion treatment with panitumumab and modified FOLFOXIRI. The hazard ratio was below 0.5. I think this data will be confirmed in a phase III trial running actually but these are the main results from the trial.
Were there any adverse effects?
Yes. I think it’s very important if one uses the modified FOLFOXIRI protocol with panitumumab always lower down the dosage of irinotecan to 150mg/m2 or better 130mg/m2 and the 5FU pump to 3,000 or 2,400. Then this protocol can be safely administered, the main toxicities are GI toxicity – mucositis, diarrhoea – together with neutropenia but with the dose modifications and sometimes the use of GCSF it can be managed very well.
How was quality of life of the patients?
Quality of life, we have first data and that will be published at ESMO. The quality of life was not different between the two arms although that was very intensive treatment.
Although it’s just a phase II trial there is a clinical impact because we have done also a central radiology review which was also published in a separate poster today. So far the early tumour shrinkage data, meaning shrinkage more than 20% at week 8, are the highest so far published. For example in the TRIBE trial, FOLFOXIRI plus bevacizumab, we had an early tumour shrinkage rate of around 59% and we have 87-88% in this trial, so a huge increase. Actually also we see the deepest responses, so the maximal shrinkage of the tumour was very, very high. Therefore this treatment, modified FOLFOXIRI plus panitumumab, in my opinion, is the optimal treatment for all patients with high tumour load, with aggressive tumour biology, high LDH and the chance of a secondary metastatic lesion resection in ECOG 0-1 patients. I think this is the best treatment because usually after three, four or a maximum of five cycles the job is done and the patient is out of danger or can be resected.
