Today glioblastoma is still an aggressive tumour. To date no efficacy drugs are against this aggressive tumour. We performed a trial called REGOMA studying regorafenib drug versus lomustine that actually is really the standard of treatment for second line glioblastoma. This is a randomised study, a multi-centre study, and ten centres in Italy were involved in this study. We used regorafenib because we know that glioblastoma is a highly angiogenesis tumour and so regorafenib is a drug against oncogenesis and stromal invasion. So regorafenib is an optimal drug for this setting of patients. So we performed this study.
How did it go, what were the outcomes?
The endpoint, the primary endpoint, was overall survival and in the study there were secondary endpoints such as progression free survival, quality of life and safety. Very interesting is that the primary endpoint, overall survival, was met. Indeed, patients treated with regorafenib had a statistically significant longer overall survival compared to the lomustine arm. These patients had a median overall survival of 6.5 months compared to 5.5 months. But very interesting is the twelve month overall survival because the patients treated with regorafenib had almost three times higher compared to the lomustine arm. So it’s very important because there was a subgroup of patients responding to regorafenib. Probably the regorafenib effective is with stable disease and so a subset of patients had stable disease during the treatment.
In terms of toxicity, any related events?
Regorafenib in general was a well-tolerated treatment. The toxicity was as expected. Indeed, in other types of tumours, such as colorectal cancer, hepatocellular carcinoma, the toxicity was higher than the toxicity shown in this trial. Moreover, the toxicity was manageable and so most of the patients continued the treatment. About 65% of patients had a grade 3/4 toxicity but it was manageable and in particular it was due to hepatic toxicity but very manageable.
Just to check, in terms of approvals and availability, is regorafenib ready to deploy? Is it clinic ready?
Now in the future we would perform a phase III study to confirm the results shown in this phase II trial. Very important is to identify the patients responding better to this drug. So very important is to find the molecular predictor or clinical factors to sign, to focus the patients, the good patients, to treat with this drug.
Are there plans for this biomarker analysis then?
Yes, we’ve studied eight biomarkers involved in the metabolism, analysed the tissue and focussed research on eight biomarkers involved in the metabolism of the tumour, in particular in the glucose metabolism because regorafenib may interfere with this metabolism. We saw that this metabolism could improve the efficacy of regorafenib.
That covers all my questions, is there anything else to add?
My comment is that this is one of the studies in this aggressive tumour demonstrating an activity and efficacy of a new drug, in this case regorafenib. In the last years, about ten years, no drugs were found with this result. So it’s very interesting, these results, and of course these results will be validated in a subsequent phase III study.