REFLECT Trial: Study Design and Key Data


Dr Gholam reviews the study design and key data from the phase 3 REFLECT trial.

Pierre Gholam, MD: The rationale for using lenvatinib in this patient we discussed comes entirely from the REFLECT study, an open-label, multicenter international trial. This was designed to look at whether lenvatinib is noninferior—that was the conclusion, at least, perhaps not the aim—compared to sorafenib in the setting of unresectable HCC [hepatocellular carcinoma]. The study included broad categories of patients, this included almost exclusively Child-Pugh A patients. Patients had to have an ECOG performance status of 0 to 1. They could not be in the study if they had more than 50% liver tumor invasion. And while they were very liberally included in the study, if they had branch portal vein invasion, they could not be included, only if they had main portal vein invasion. Everybody else with macrovascular invasion was allowed in this study.

The study concluded that lenvatinib was noninferior to sorafenib, with significant improvements in both objective response rate, as well as progression-free survival, both of which were considerably greater with lenvatinib versus sorafenib. Based on these data, the FDA approved the drug as a first-line option in the treatment of HCC. We have had additional interesting information, including some from the most recent ASCO [American Society of Clinical Oncology] meeting, which just occurred. One is a subset of patients that were analyzed by [Amit] Singal, [MD, MS,] and colleagues regarding real-world effectiveness of lenvatinib monotherapy in the United States. This is an analysis of a group of patients whose course and outcomes were recorded.

I will note very interestingly about this, it does include a significant number of Child-Pugh B patients. Those are patients who not only have cirrhosis but typically have some sign of decompensation, the earliest of which would be ascites. That’s an interesting group of patients because we often grapple with what to do with these, and they probably represent easily 30% of the patients we see who have unresectable HCC that present to our offices. They are a very relevant group of patients to address. In this study, there does appear to be a preservation of the benefits of Lenvima in the broader group. It reaffirms some of the objective parameters that REFLECT demonstrated for Lenvima, including overall survival, objective response rate, a fairly generous complete response, interestingly, within that subset, and progression-free survival. Based on that selected group, this is not a randomized group of patients by any means, it does appear to be at minimum a reaffirmation of the end points and parameters shown in REFLECT.

There’s a second study along the same lines from a consortium of 10 Canadian cancer centers. This essentially is another real-world analysis that looks at the efficacy and safety of lenvatinib, and shows more or less the same thing. Again, this is a confirmation of these known improvements in the end points of treatment of unresectable HCC in the setting of a real-world Canadian multicenter database. That certainly is my experience in patients with unresectable HCC who receive lenvatinib, as long as the liabilities in terms of adverse events are accounted for. We’re talking about hypertension. We’re talking about monitoring for potential toxicities and improving adherence to treatment. I think the drug performs as on label in the setting of unresectable HCC and could be a very viable treatment option in that setting.

Transcript edited for clarity.

A 61-Year-Old Woman with Hepatocellular Carcinoma

Initial Presentation

  • A 61-year-old woman complains of fatigue, RUQ pain and nausea and vomiting
  • PMH: medically controlled hypertension; obesity; diabetes managed with oral medication
  • PE: hepatomegaly with tenderness over the RUQ

Clinical Workup

  • CT scan of chest, abdomen and pelvis, with 4 phase liver evaluation: 4.0-cm hepatic mass in the right hepatic lobe
  • Labs: AFP: 1.5 ng/dL; Alb: 3.9 g/dL; INR: 1.45; Bili: 1.1 mg/dL , HbA1c: 7.0; platelet count 90,000
  • Biopsy of the lung metastasis demonstrated evident hepatocellular carcinoma
  • Child-Pugh A
  • ECOG PS 1


  • Initiated lenvatinib 12 mg QD

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