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

The phase 2 REGINA trial has yielded encouraging results for the use of neoadjuvant regorafenib together with nivolumab and short-course radiotherapy (SCRT) in treating 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 short-course radiotherapy (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 standard nivolumab and SCRT treatments. The primary endpoint for REGINA is 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; 8 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 GI, 26-29 June 2024. Munich, Germany.

Medical writing support was provided by Dr Rachel Giles.
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Posted on 2 July 20242 July 2024