Real-World Outcomes of Regorafenib for mCRC Reflect Clinical Trials

Patients with metastatic colorectal cancer (mCRC) treated in the real-world setting experienced comparable survival benefits and safety outcomes compared with clinical trials, despite more than half of patients starting on a dose lower than the approved dose, according to a presentation at the ESMO World Congress on Gastrointestinal Cancer (June 20-23; Barcelona, Spain).

In the randomized, phase III CORRECT and CONCUR trials, regorafenib significantly improved overall survival (OS) versus placebo in patients with mCRC who progressed on standard therapies. CORRELATE was a prospective, observational study with the aim of characterizing the real-world use of regorafenib for the treatment of mCRC in clinical practices across 13 countries. Michel Ducreux, Gustave Roussy Cancer Campus Grand Paris (Villejuif, France), presented the final analysis from the study.

Patients enrolled in the trial had mCRC and were previously treated with approved therapies. The decision to treat with regorafenib must have been made by the treating physician prior to enrollment. Dose interruptions and reductions were permitted for the management of adverse events (AEs). The study evaluated the incidence of treatment-emergent AEs (TEAEs) as a primary endpoint, as well as OS, progression-free survival (PFS), and the disease control rate (DCR) as secondary endpoints.

A total of 1037 patients (61% male, 39% female) were included in the analysis. Baseline patient characteristics were typical of patients with mCRC, Dr Ducreaux observed. At study entry, the median age was 65 years (range: 24–93), most patients were ECOG PS 0–1 (87%) versus PS 2–4 (6%), 56% had KRAS mutations and 37% did not, and the most common metastatic sites were the liver (72%) and the lung (57%). Dr Ducreaux noted that it was very common among patients in the study group to have received 4 or more prior lines of systemic therapy (39% of patients), while 30% received 3 prior lines and 30% received 2 prior lines.

The recommended dose of regorafenib is 160 mg daily administered 3 weeks on/1 week off. However, decisions by physicians to modify the dose of regorafenib were common. The initial daily regorafenib dose was 160 mg in 57% of patients, while 30% and 12% of patients had initial doses of 120 mg and 80 mg, respectively. Overall, 40% of patients had dose reductions and 48% had a dose interruption or delay, while 35% had no dose modifications. The median treatment duration was 2.5 months (range: 0.03–29.5).

TEAEs Grade 3 or greater occurred in 62% of patients and were attributed to regorafenib in 36% of patients. “We observed exactly the same pattern of toxicity as in the clinical trial,” Dr Ducreaux reported. The most common of these TEAEs were fatigue (10%), hypertension (8%), and hand–foot skin reaction (HFSR; 7%), with most being regorafenib related (fatigue 9%; HFSR 7%; hypertension 6%). Dr Ducreaux noted that the HFSR rate was lower than that reported in the clinical trial.

The study was also consistent with the clinical trial in terms of the survival outcomes, which is notable given the non-selected patient population, Dr Ducreaux said. Median OS was 7.6 months (95% CI: 7.1–8.2) and median PFS was 2.8 months (95% CI: 2.6–2.8). DCR was 21.0% by radiologic assessment, with a partial response in 3.1% of patients as best response.

Dr Ducreaux also gave a preview of the study group’s analysis of the relationship between regorafenib dose and outcomes. Surprisingly, no clear differences were observed between patients given different initial doses (160 mg, 120 mg, or 80 mg) in terms of their baseline characteristics. Further analyses are being done to determine the relationship between the initial dose, the last daily dose, and survival outcomes.

The study’s findings are encouraging, Dr Ducreaux concluded, given that median OS and PFS were in the range observed in phase III trials despite great flexibility in regorafenib dosing, and AEs were generally consistent with the known safety profile of regorafenib in mCRC.—Kara Rosania