Results of REARRANGE trial: A randomized phase 2 study comparing different dosing approaches for regorafenib (REG) during the first cycle of treatment in patients (pts) with metastatic colorectal cancer (mCRC)

Argilés, Guillem; Margalef, N. Mulet; Valladares‐Ayerbes, Manuel; Prado, J. Vieitez de; Grávalos, Cristina; Alfonso, Pilar; Santos, Catarina; Tobeña, M.; Sastre, Javier; Benavides, Manuel; Cano, T.; Loupakis, Fotios; Garrote, M. Rodriguez; Rivera, Fernando; Goldberg, Richard M.; Falcone, Alfredo; Bennouna, Jaafar; Tabernero, Josep; Aranda, Enrique

doi:10.1093/annonc/mdz154.025

Cited by 22 publications

(18 citation statements)

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“…In real-world studies, overall treatment effectiveness in patients initiated on a lower regorafenib dose, therefore requiring fewer doses reductions to manage AEs, remained similar to that observed in clinical trials [20][21][22][23]. The potential benefit of starting regorafenib at a lower dose in Cycle 1 is being investigated in three phase 2 dose-adaptation trials, ReDOS, REGOCC-12, and REARRANGE [30][31][32]. ReDOS was a randomized study (N = 123) designed to evaluate weekly dose escalation in Cycle 1 (from 80 mg to 160 mg/day) versus standard 160 mg/day dosing [30].…”

Section: Dose-optimization Strategiesmentioning

confidence: 69%

“…Dose optimization may also have an impact on treatment duration, with no adverse impact on outcome; in the phase 2 ReDOS study, more patients in the dose-escalation arm initiated Cycle 3 compared with the standard regimen, and OS was 9.8 versus 6.0 months (HR = 0.72; P = 0.12), respectively [30]. Other dose-optimization studies, REGOCC-12 and REARRANGE (Table 1) [31,32], are discussed further in the Dose-optimization strategies section.…”

Section: Mcrcmentioning

confidence: 99%

“…Grade ≥ 3 AEs were observed in 55% of patients receiving regorafenib in REGOCC-12, versus 80% (Japanese) and 51% (non-Japanese) receiving regorafenib in CORRECT [18]. The randomized, phase 2 REARRANGE study (N = 299) compared dosing approaches for regorafenib during Cycle 1 in patients with refractory mCRC [32]. Although the study failed to meet its primary endpoint of improving tolerability through a reduced regorafenib dose of 120 mg/day (3 weeks on/1 week off) or an intermittent 160 mg/day dose (1 week on/1 week off), it showed a numerical improvement in relevant AEs including fatigue, HFSR, and hypertension, without jeopardizing efficacy [32].…”

Section: Dose-optimization Strategiesmentioning

confidence: 99%

“…The randomized, phase 2 REARRANGE study (N = 299) compared dosing approaches for regorafenib during Cycle 1 in patients with refractory mCRC [32]. Although the study failed to meet its primary endpoint of improving tolerability through a reduced regorafenib dose of 120 mg/day (3 weeks on/1 week off) or an intermittent 160 mg/day dose (1 week on/1 week off), it showed a numerical improvement in relevant AEs including fatigue, HFSR, and hypertension, without jeopardizing efficacy [32]. The results from these studies suggest that a flexible first-cycle dose-optimization approach may help some patients with mCRC to manage toxicity and stay on treatment.…”

Section: Dose-optimization Strategiesmentioning

confidence: 99%

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Evolving role of regorafenib for the treatment of advanced cancers

Grothey

Blay

Pavlakis

et al. 2020

Cancer Treatment Reviews

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Regorafenib is an oral tyrosine kinase inhibitor (TKI) approved for the treatment of refractory metastatic colorectal cancer (mCRC), advanced gastrointestinal stromal tumors (GIST) previously treated with imatinib and sunitinib, and unresectable hepatocellular carcinoma (HCC) following progression on sorafenib. Regorafenib was initially approved for mCRC based on improved overall survival (OS) in the randomized, placebo-controlled, phase 3 CORRECT trial, which was confirmed in an expanded population of Asian patients in the randomized, placebo-controlled phase 3 CONCUR trial. Approvals in GIST, and more recently in HCC, were based on the results from the randomized, placebocontrolled, phase 3 GRID and RESORCE trials, respectively. In this review, we provide a comprehensive summary of the clinical evidence for approval of regorafenib in mCRC, GIST, and HCC, present emerging evidence of regorafenib activity in other tumor types (namely, gastroesophageal cancer, sarcomas, biliary tract cancer, and glioblastoma), and discuss trials in progress within the context of regorafenib's mechanism of action. We describe recent advances and key lessons learned with regorafenib, including the importance of managing common drug-related toxicities using doseoptimization strategies, the search for biomarkers to predict response to treatment, and highlight some of the unaddressed questions and future directions for regorafenib across tumors.

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Section: Dose-optimization Strategiesmentioning

confidence: 69%

Section: Mcrcmentioning

confidence: 99%

Section: Dose-optimization Strategiesmentioning

confidence: 99%

Section: Dose-optimization Strategiesmentioning

confidence: 99%

See 2 more Smart Citations

Evolving role of regorafenib for the treatment of advanced cancers

Grothey

Blay

Pavlakis

et al. 2020

Cancer Treatment Reviews

View full text Add to dashboard Cite

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“…29 The percentage of patients who started the third cycle with 160 mg/d was significantly higher in the experimental arm and, in addition, they had longer OS, better QoL, and less G3 to 4 toxicities (high blood pressure, 7% vs. 15% and asthenia, 13% vs. 18%). In the REARRANGE study, 30 flexible dosing showed numerical improvement on several parameters that improved tolerance, such as fatigue, hypertension, or hand-foot syndrome, although the study did not meet its primary endpoint of improving regorafenib global tolerability in the reduced-and intermittent-dose groups. The average treatment duration was 3.2 months in the standard group; 3.7 months in the reduced-dose group; and 3.8 months in that with alternating weeks.…”

Section: Regorafenibmentioning

confidence: 99%

Current Options for Third-line and Beyond Treatment of Metastatic Colorectal Cancer. Spanish TTD Group Expert Opinion

Férnández-Montes

Grávalos

Pericay

et al. 2020

Clinical Colorectal Cancer

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Colorectal cancer (CRC) is a public health problem: it is the third most common cancer in men (746,000 new cases/ year) and the second in women (614,000 new cases/year), representing the second leading cause of death by cancer worldwide. The survival of patients with metastatic CRC (mCRC) has increased prominently in recent years, reaching a median of 25 to 30 months. A growing number of patients with mCRC are candidates to receive a treatment in third line or beyond, although the optimal drug regimen and sequence are still unknown. In this situation of refractoriness, there are several alternatives: (1) To administer sequentially the 2 oral drugs approved in this indication: trifluridine/ tipiracil and regorafenib, which have shown a statistically significant benefit in progression-free survival and overall survival with a different toxicity profile. (2) To administer cetuximab or panitumumab in treatment-naive patients with RAS wild type, which is increasingly rare because these drugs are usually indicated in firstor second-line. (3) To reuse drugs already administered that were discontinued owing to toxicity or progression (oxaliplatin, irinotecan, fluoropyrimidine, antiangiogenics, anti-epidermal growth factor receptor [if RAS wild-type]). High-quality evidence is limited, but this strategy is often used in routine clinical practice in the absence of alternative therapies especially in patients with good performance status. (4) To use specific treatments for very selected populations, such as trastuzumab/lapatinib in mCRC human epidermal growth factor receptor 2-positive, immunotherapy in microsatellite instability, intrahepatic therapies in limited disease or primarily located in the liver, although the main recommendation is to include patients in clinical trials.

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