NUTLEY, N.J., June 27, 2024-- Eisai today announced results from a post-hoc analysis from the Phase 3 REFLECT trial, which looked at efficacy outcomes characterized by depth of response in patients with unresectable hepatocellular carcinoma (uHCC) treated with LENVIMA® (lenvatinib) as a first-line systemic therapy. This analysis shows that median overall survival (OS) in patients treated with LENVIMA who achieved a near-complete response (near-CR) was similar to that of patients who experienced a complete response (CR). These data are being presented in a poster display session (#168P) at the 2024 European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress, which is taking place in Munich from June 26–29.
Of the 478 patients randomly assigned to receive LENVIMA in the REFLECT trial, 194 patients (41%) had an objective response, as assessed by independent imaging review per mRECIST, and were included in this analysis; the statistics of this post-hoc analysis are descriptive in nature. Of the 194 patients who had an objective response, 10 had a CR and 184 had a partial response ([PR]: 49 had a near-CR with ≥75% TLR (target lesion reduction); 72 had a PR with ≥50% to <75% TLR; and 63 had a PR with ≥30% to <50% TLR).
In the analysis, OS was similar for patients with CR (25.4 months; 95% CI: 5.5–NE [not estimable]) and near-CR (23.4 months; 95% CI: 12.0–30.1), which were higher compared to patients with PR with ≥50% to <75% TLR (19.8 months; 95% CI: 14.1–23.1) and PR with ≥30% to <50% TLR (14.4 months; 95% CI: 13.1–19.1). OS rates at 12 and 24 months, respectively, were:
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CR: 80.0% (95% CI: 40.9-94.6) and 60.0% (95% CI: 25.3-82.7);
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near-CR with ≥75% TLR: 63.2% (95% CI: 48.1-75) and 48.0% (95% CI: 33.3-61.2);
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PR with ≥50% to <75% TLR: 70.8% (95% CI: 58.9-79.9) and 37.4% (95% CI: 25.7-49.0); and
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PR with ≥30% to <50% TLR: 67.2% (95% CI: 53.9-77.5) and 30.4% (95% CI: 19.3-42.3).
The median duration of response (DOR) was 20.3 months (95% CI: 4.7-NE) for patients with CR. Median DOR was similar among patients with near-CR and PR with ≥50% to <75% TLR, 7.7 months (95% CI: 6.9-9.2) and 7.3 months (95% CI: 5.5-7.4), respectively; while patients with PR with ≥30% to <50% TLR had a median DOR of 3.7 months (95% CI: 3.7-5.6). Of patients with near-CR, 10.2% maintained their response for more than 18 months, and 8.3% of patients with PR with ≥50% to <75% TLR maintained their response for more than 18 months.
"This study, the first to examine near-complete response in this disease, demonstrates that LENVIMA may help these patients live nearly as long as those with a complete response, reinforcing the important role of LENVIMA as a first-line treatment for unresectable hepatocellular carcinoma," said Dr. Takashi Owa, Chief Scientific Officer, Senior Vice President, Eisai Co., Ltd. "These data add to the existing body of knowledge on the activity of LENVIMA in first-line unresectable HCC, which may aid healthcare providers in identifying the most appropriate treatment options for their patients and we're grateful to our investigators for their commitment to this goal."
Improved progression-free survival (PFS) was observed in patients with CR (22.1 months; 95% CI: 6.4-NE) compared to patients with any PR [near-CR: 10.5 months (95% CI: 9.1–11.1); PR with ≥50% to <75% TLR: 9.2 months (95% CI: 7.4–11.1); PR with ≥30% to <50% TLR: 7.4 months (95% CI: 5.5–9.2)].
LENVIMA was approved by the U.S. Food and Drug Administration (FDA) in August 2018 for the treatment of patients with unresectable hepatocellular carcinoma (HCC) based on data from the REFLECT trial.
About the REFLECT Trial (Study 304)
REFLECT was an international, multicenter, randomized, open-label, non-inferiority Phase 3 study to compare the efficacy and safety of LENVIMA versus sorafenib as a first-line systemic treatment in patients with uHCC. Patients (n=954) at 183 trial sites in 21 countries were randomized to receive LENVIMA 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was overall survival. LENVIMA showed non-inferior overall survival compared to sorafenib (median OS for patients treated with LENVIMA was 13.6 months compared to 12.3 months for sorafenib [HR: 0.92; 95% CI: 0.79 – 1.06]). Patients randomized to the LENVIMA arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. The secondary efficacy endpoints of this study were progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR). Independent imaging review based on mRECIST criteria confirmed superiority of LENVIMA to sorafenib on these three tumor response assessments: median PFS with LENVIMA was 7.3 months vs. 3.6 months in the sorafenib arm (HR: 0.64; 95% CI: 0.55-0.75; p<0.001); median TTP with LENVIMA was 7.4 months vs. 3.7 months in the sorafenib arm (HR: 0.60; 95% CI: 0.51-0.71; p<0.0001); ORR with LENVIMA was 41% vs. 12% in the sorafenib arm (odds ratio: 5.01; 95% CI: 3.59-7.01; p<0.001).
The analysis presented at ESMO GI 2024 characterized OS, PFS and duration of response outcomes among the 194 responders with a complete or partial response to LENVIMA (as assessed by independent imaging review per mRECIST), grouped based on their degree of tumor size reduction at best overall response.
About Hepatocellular Carcinoma (HCC)
Hepatocellular carcinoma is the most common type of primary liver cancer and in the United States, liver cancer incidence rates have tripled over the past four decades. Hepatocellular carcinoma accounts for approximately 90% of primary liver cancers. It is estimated that there were more than 866,000 new cases of liver cancer and more than 758,000 deaths from the disease globally in 2022, making it the sixth most frequently diagnosed cancer worldwide and one of the leading causes of cancer deaths around the world. In the United States, it is estimated there will be over 41,000 new cases of liver cancer and approximately 30,000 deaths from this disease in 2024. Risk factors for liver cancer include gender, ethnicity, chronic viral hepatitis (Hep-B or Hep-C) infection, cirrhosis, alcohol use and metabolic syndrome. Hepatocellular carcinoma, which is often diagnosed at an advanced stage, has a five-year relative survival rate of approximately 22% in the United States.
About LENVIMA® (lenvatinib) Capsules
LENVIMA is indicated:
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For the treatment of adult patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC)
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In combination with pembrolizumab, for the first line treatment of adult patients with advanced renal cell carcinoma (RCC)
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In combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
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For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)
In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma (EC) that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
LENVIMA, discovered and developed by Eisai, is a multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRA), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2 alpha (FRS2) phosphorylation. In syngeneic mouse tumor models, the combination of lenvatinib with an anti-PD-1 monoclonal antibody decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity compared to either treatment alone. The combination of LENVIMA and everolimus showed increased antiangiogenic and antitumor activity as demonstrated by decreased human endothelial cell proliferation, tube formation, and VEGF signaling in vitro and tumor volume in mouse xenograft models of human renal cell cancer greater than each drug alone.
About Eisai
Eisai's Corporate Concept is "to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides." Under this Concept [also known as our human health care (hhc) Concept], we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.