REGINA meets stage 1 endpoint in rectal cancer and moves to stage 2 with reduced dose regorafenib

The phase 2 REGINA trial yielded encouraging results for the use of neoadjuvant regorafenib together with nivolumab and short-course radiotherapy (SCRT) as a treatment for patients with stage II–III rectal cancer, although toxicities were more common than anticipated.

Regorafenib, an oral multi-kinase inhibitor, targets angiogenic, stromal, and oncogenic receptor tyrosine kinases. Dr Francesco Sclafani (Institut Jules Bordet, Belgium) presented the interim analysis of the REGINA trial (NCT04503694), which investigated the triplet combination of neoadjuvant regorafenib, nivolumab, and SCRT in 36 patients with stage II–III rectal cancer [1]. Participants received 160 mg of regorafenib daily for 3 weeks, followed by a 1-week break, in repeated 28-day cycles, in addition to nivolumab and SCRT treatments. The primary endpoint is the pathological and clinical complete response (pCR and cCR) at 1 year.

The predefined statistical criteria for this interim analysis were met, supporting further investigation of the combination of regorafenib, nivolumab, and SCRT as neoadjuvant therapy for locally advanced rectal cancer. Promising pCR rates and “watch & wait” adoption were observed regardless of mismatch repair or microsatellite stability (MMR/MSS; n=30) status. Of the 36 participants, 8 achieved cCR prior to surgery and moved to “watch & wait”, while 27 underwent surgery. Eight of those participants (30%) achieved pCR, concluding that over one-third (16/36, 44%) of the study population achieved pCR or cCR with this approach.

Given an unexpectedly high toxicity rate, in the second stage of the study the regorafenib dose will be reduced to 60 mg/day in hopes of improving the treatment safety profile. The nature of adverse events was consistent with known profiles, including hand-foot skin reaction, hypertension, and fatigue. Importantly, the trial reported no new safety concerns.

Dr Sclafani concluded: “The phase 2 REGINA trial brings both challenges and hope. The 60% incidence of grade ≥3 serious adverse events underscores the need for meticulous patient management, while a 25% pCR in MRR/MSS patients is promising. Balancing efficacy and toxicity remains crucial.”

1. Sclafani F, et al. Efficacy interim analysis of REGINA, a phase II trial of neoadjuvant regorafenib (Rego), nivolumab (Nivo), and short-course radiotherapy (SCRT) in stage II-III rectal cancer (RC). Abstract LBA2, ESMO Gastrointestinal Cancers Congress 2024, 26–29 June, Munich, Germany.

Copyright ©2024 Medicom Medical Publishers



Posted on 21 August 202421 August 2024