The combination of regorafenib, nivolumab and SCRT shows promising efficacy as neoadjuvant therapy for locally advanced RC
Dr Francesco Sclafani - Institut Jules Bordet, Brussels, Belgium
The REGINA study is an ongoing single-arm phase II study testing the combination of nivolumab plus regorafenib and short-course radiotherapy for patients with stage II or III rectal cancer.
What was the study design?
Patients who were recruited into the REGINA study, they were treated with an induction treatment including two administrations of nivolumab, 240mg once every two weeks, and regorafenib, 80mg once daily for two weeks. Then, they received a short-course of radiotherapy, so 25Gy in five fractions, and then again they received a systemic treatment, a consolidation therapy including three administrations of nivolumab, 240mg once every two weeks, and three weeks of regorafenib at a dose of 80mg once daily. Then, a few weeks later, patients had either surgery or they could opt for watch and wait if the reassessment scans showed clinical complete response. Then, the use of adjuvant chemotherapy for those patients who had surgery was left to the discretion of the investigator.
What were the results of this study?
At this stage, we have completed the first part of the study, because the study has a Simon two-stage design and we have got the interim data from the first 36 patients. First of all, in terms of efficacy we had quite interesting results because in the entire patient population we had 30% of patients who had a pathological complete response, 64% of patients who had a major pathological response, so what we call a tumour regression grade 3 or 4 according to the Dvorak system. But then, we had also 8 patients who had a clinical complete response and they are currently managed with a watch and wait approach. The most interesting result, though, comes from the patient population with mismatch-repair proficient or microsatellite stable tumours, because out of the 36 patients recruited in the study, 30 patients had mismatch-repair proficient or microsatellite stable tumours. Of these 30 patients, 24 had surgery and six, so 25% of them, had a pathological complete response. 58% had a major pathological response. There are an additional five patients who had a clinical complete response and are currently managed with a watch and wait strategy.
These are the activity and efficacy data. When it comes to the safety data, we had approximately 60% of patients who had a grade 3 or higher adverse event and approximately, again, 60% of patients who had a serious adverse event. The most common toxicity were gastrointestinal disorders.
What is the clinical impact of these results?
The preliminary results of the REGINA trial are quite promising, because we have seen a rate of complete response or other pathological or clinical complete response which is definitely higher than what we would normally expect when we treat patients by short-course radiotherapy only. However, the study is still ongoing, and of course these preliminary results will need to be confirmed in the second part of the study, and of course in a larger independent series. We have to acknowledge that, because the study is still ongoing, this is a non-randomised study. Of course, ideally, we would need to compare this investigational combination treatment against standard of care therapy.
The other thing is that we have seen quite a unexpectedly high rate of serious adverse events and severe adverse events, likely related to the combination treatment, and this is why in the second part of the study we will reduce the dose of regorafenib from 80mg to 60mg per day to hopefully improve the overall treatment safety profile.
