Further Evaluation of Regorafenib/Nivolumab Is Recommended in Rectal Cancer
An interim analysis of the phase 2 REGINA trial met predefined statistical criteria and suggests the need for further evaluation of the combination of regorafenib, nivolumab, and short-course radiation therapy in patients with locally advanced rectal cancer.
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An interim analysis of the phase 2 REGINA trial (NCT04503694) met predefined statistical criteria and suggests the need for further evaluation of the combination of regorafenib (Stivarga), nivolumab (Opdivo), and short-course radiation therapy in patients with locally advanced rectal cancer.
“Despite improvements in the way we treat rectal cancer, we still need novel treatment strategies to improve outcomes for these patients,” Francesco Sclafani, MD, a consultant medical oncologist at the Institut Jules Bordet, Brussels, Belgium, said during a presentation of the data at the European Society for Medical Oncology Gastrointestinal Cancers Congress, June 26 to 29, 2024, in Munich, Germany.
REGINA is a single-arm study in which patients with stage II and III rectal cancer with either proficient mismatch repair status or who are mismatch repair deficient (dMMR) are treated with an induction phase of 240 mg of nivolumab every 2 weeks for a total of 2 doses and 80 mg of regorafenib for 2 weeks. After these first 2 weeks of induction treatment, patients receive a short course of radiotherapy, followed by a consolidation treatment. Seven to nine weeks after receiving radiation, patients undergo surgery.
The primary end point is complete response (CR) consisting of a pathologic CR and a clinical CR and there are 2 safety interim analyses planned after 6 and 12 patients are accrued.
“In the first stage of the study, we had to recruit 36 patients. In order to move to the second part of the study, we had to have at least 5 patients with CR,” Sclafani said.
Half of the 36 patients were male, and the median age was 64.5 years. There were 89% of patients who had an ECOG performance status of 0.
“I would like to point out that the majority of patients were cT3 stage [92%] and lymph node positive,” Sclafani said. “Forty-four percent had more than 1 RAPIDO [Rectal Cancer and Preoperative Induction Therapy Followed by Dedicated Operation] high-risk feature, and 5 patients [14%] had dMMR/microsatellite instability-high tumors,” continued Sclafani.
Sclafani said that 83% of patients completed induction therapy, and of those, 97% completed the short course of radiotherapy. A total of 94% of patients started consolidation therapy with 61% completing that stage of treatment. Treatment delays due to toxicity occurred in 6% of patients who received radiotherapy and 14% of patients who underwent surgery.
Reviewing aggregate safety data, all patients experienced any-grade adverse events (AEs) with 61% experiencing grade 3 or higher AEs and 56% experiencing grade 3 or higher treatment-related AEs (TRAEs). Sixty-four percent had serious AEs with 53% of patients experiencing serious TRAEs.
“The data on complications, any grade post-operation or grade 3 or higher post-operation, were in line with what we would normally expect for this patient population,” Sclafani said.
Regarding the most common any-grade AEs, 92% of patients reported gastrointestinal disorders, followed by general disorders and administration site conditions (69%), metabolism and nutrition disorders (58%), and musculoskeletal and connective tissue disorders (58%). The grade 3 events for these most common AEs were 28%, 14%, 17%, and 11%, respectively.
Among the 36 patients enrolled, 27 patients underwent surgery. Of these patients, 30% had a pathologic CR (pCR), 64% had a major pCR, and 8 patients had a clinical CR and opted for watch and wait treatment.
Reviewing patients with proficient mismatch repair, 24 had surgery; of these, 25% had a CR, 58% had a major pCR, and 5 patients were treated with a watch and wait strategy.
“In the second part of the study, we have seen a promising rate of pCR and watch and weight adoption,” Sclafani said. “This was irrespective of the mismatch repair status of these patients.”
Because of the unexpectedly high toxicity rate in the second part of the study, the dose of regorafenib will be reduced to 60 mg per day to improve the safety profile, Sclafani said.
