LuciLenva lenvatinib 4mg/10mg

Product Name: LuciLenva

Chinese Name: Lenvatinib

English Name: Lenvatinib

Specifications: 4 mg/capsule (30 capsules/box); 10 mg/capsule (30 capsules/box)

[Overview]

Lenvatinib is a multi-targeted inhibitor; its targets include VEGFR-1, VEGFR-2, VEGFR-3, FGFR1, PDGFR, cKit, and Ret. It is approved for the treatment of patients with differentiated thyroid cancer (DTC), renal cell carcinoma (RCC), and hepatocellular carcinoma (HCC).

[Indications]

1. Differentiated Thyroid Cancer (DTC): Indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioiodine-refractory differentiated thyroid cancer (DTC).

2. Renal Cell Carcinoma (RCC): In combination with the monoclonal antibody pembrolizumab, indicated for adult patients with advanced renal cell carcinoma (RCC). In combination with everolimus, indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received one prior anti-angiogenic therapy.

3. Hepatocellular Carcinoma (HCC): Indicated for patients with unresectable hepatocellular carcinoma (HCC).

4. Endometrial Carcinoma (EC): In combination with pembrolizumab, indicated for the treatment of patients with advanced endometrial carcinoma (EC).

[Storage]

Store in a dry place at 20°C to 25°C. Excursions are permitted between 15°C and 30°C (59°F and 86°F).

[Dosage and Administration]

I. Monotherapy:

1. DTC: The recommended dosage is 24 mg, taken orally once daily.

2. HCC: The recommended dosage is based on actual body weight: 12 mg orally once daily for patients weighing 60 kg or more; 8 mg orally once daily for patients weighing less than 60 kg.

II. Combination Therapy:

1. EC: The recommended dosage is 20 mg, taken orally once daily, in combination with 200 mg of pembrolizumab.

2. RCC: The recommended dosage is:

① In combination with pembrolizumab: 20 mg orally once daily. ②. When used in combination with everolimus: Administer orally once daily at a dose of 18 mg.

[Adverse Reactions]

The most common adverse reactions associated with lenvatinib (incidence rate ≥ 30%) include hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, weight loss, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, dysphonia, etc.

[Warnings and Precautions]

1. Hypertension:

Blood pressure requires therapeutic control. Grade 3 hypertension requires optimal antihypertensive treatment. Discontinue the drug in cases of life-threatening hypertension.

2. Heart Failure:

Monitor for clinical symptoms or signs of cardiac decompensation. Exercise caution when administering to patients with Grade 3 cardiac dysfunction; discontinue the drug in cases of Grade 4 cardiac dysfunction.

3. Arterial Thromboembolic Events:

Discontinue the drug upon the occurrence of an arterial thromboembolic event.

4. Hepatotoxicity:

Monitor liver function prior to initiating lenvatinib and periodically throughout the course of treatment. Exercise caution in patients with Grade 3 or higher hepatic impairment; discontinue the drug in cases of hepatic failure.

5. Proteinuria:

Monitor for proteinuria prior to initiating lenvatinib and periodically throughout treatment. For proteinuria ≥ 2 g/24 hours, reduce the dosage; discontinue the drug in cases of nephrotic syndrome.

6. Diarrhea:

May be severe and recurrent. Use standard antidiarrheal treatments. Reduce the dosage for Grade 3 diarrhea; discontinue the drug for Grade 4 diarrhea.

7. Renal Failure and Impairment:

Suspend administration in cases of Grade 3 or 4 renal failure or impairment.

8. Gastrointestinal Perforation and Fistula Formation:

Discontinue the drug in patients who develop gastrointestinal perforation or a life-threatening fistula.

9. QT Interval Prolongation:

Monitor for and correct electrolyte abnormalities. Exercise caution in cases of Grade 3 or higher QT interval prolongation.

10. Hypocalcemia:

Monitor serum calcium levels; administer calcium supplementation at least monthly and replace as necessary.

11. Reversible Posterior Leukoencephalopathy Syndrome (RPLS):

Suspend administration until symptoms have completely resolved. 12. Hemorrhagic Events:

For Grade 3 hemorrhage, suspend treatment; for Grade 4 hemorrhage, discontinue treatment.

13. Thyroid-Stimulating Hormone (TSH) Suppression and Thyroid Dysfunction:

Monitor TSH levels; monthly monitoring and the use of thyroid replacement therapy are required.

14. Embryo-Fetal Toxicity:

May cause harm to the fetus. Inform patients of the potential risks and advise the use of effective contraception. If taken during lactation, discontinue breastfeeding.

[Clinical Data]

1. Lenvatinib Data for Thyroid Cancer

1) Median Progression-Free Survival (mPFS) was 18.3 months in the Lenvatinib group vs. 3.6 months in the placebo group;

2) The Objective Response Rate was 64.8% in the Lenvatinib group vs. 1.5% in the placebo group.

2. Lenvatinib Data for Renal Cell Carcinoma

1) Median Progression-Free Survival (mPFS) was 14.6 months in the Lenvatinib + Everolimus combination therapy group vs. 5.5 months in the Everolimus monotherapy group;

2) Overall Survival (OS) was 25.5 months in the Lenvatinib + Everolimus combination therapy group vs. 15.4 months in the Everolimus monotherapy group;

3) The Objective Response Rate was 37% in the Lenvatinib + Everolimus combination therapy group vs. 6% in the Everolimus monotherapy group.

3. Lenvatinib Data for Hepatocellular Carcinoma (HCC)

On June 4, 2017 (local time in Chicago), at the Annual Meeting of the American Society of Clinical Oncology (ASCO), results were presented for the first time regarding the REFLECT study—a randomized, open-label, non-inferiority Phase III clinical trial evaluating Lenvatinib as a first-line treatment for unresectable HCC (uHCC).

The study enrolled a total of 954 patients with uHCC who had not received prior systemic therapy (meeting criteria: ≥ 1 measurable target lesion, Barcelona Clinic Liver Cancer [BCLC] stage B or C, Child-Pugh Class A, and ECOG Performance Status ≤ 1). Patients were randomized to either the Lenvatinib group (478 patients; dosage: 12 mg once daily [qd] for patients weighing ≥ 60 kg, or 8 mg qd for patients weighing < 60 kg) or the Sorafenib group (476 patients; dosage: 400 mg twice daily [bid]). In terms of overall survival (OS), Lenvatinib demonstrated non-inferiority compared to Sorafenib, with median OS values of 13.6 months and 12.3 months, respectively; furthermore, subgroup analyses indicated that among the Asia-Pacific population, first-line Lenvatinib treatment yielded superior OS benefits compared to Sorafenib treatment.

As a first-line treatment regimen for unresectable HCC (uHCC), Lenvatinib and Sorafenib demonstrated statistically and clinically significant differences across PFS, TTP, and ORR endpoints. In the Lenvatinib group, the median PFS was double that of the Sorafenib group (7.4 months vs. 3.7 months; p < 0.00001), the ORR was nearly three times that of Sorafenib (24.1% vs. 9.2%; p < 0.00001), and the median TTP (time to disease progression) was more than double that of Sorafenib (8.9 months vs. 3.7 months; p < 0.00001).

Regarding safety, the number of patients experiencing treatment-emergent adverse events (TEAEs) was similar in both groups. The most common TEAEs associated with Lenvatinib were hypertension (42%), diarrhea (39%), decreased appetite (34%), weight loss (31%), and fatigue (30)—findings consistent with previously reported adverse event profiles for Lenvatinib.

The median duration of treatment for the Lenvatinib and Sorafenib groups was 5.7 months and 3.7 months, respectively. In each group, 13% and 9% of patients, respectively, discontinued treatment due to adverse events, while 33% and 39% of patients, respectively, subsequently received second-line therapy. 4. Lenvatinib Data for Hepatocellular Carcinoma: Chinese Subgroup Analysis

The REFLECT study was a global, multicenter, randomized, open-label, non-inferiority Phase III clinical trial. It enrolled a total of 954 patients with previously untreated, unresectable hepatocellular carcinoma (HCC)—including nearly 300 patients from China (Mainland, Taiwan, and Hong Kong SAR)—with the aim of evaluating the efficacy and safety of lenvatinib as a first-line treatment compared to the current standard of care, sorafenib.

The subgroup analysis of Chinese patients demonstrated that, compared to the median overall survival (OS) of 10.2 months in the sorafenib group, the lenvatinib group significantly extended the median OS to 15.0 months, while simultaneously achieving a significant 27% reduction in the risk of death (HR 0.73).

Regarding secondary endpoints, compared to the sorafenib group, patients in the lenvatinib group experienced significant extensions in both median progression-free survival (PFS: 9.2 vs. 3.6 months; HR 0.55) and median time to disease progression (TTP: 11.0 vs. 3.7 months; HR 0.53)—results that were even more favorable than those observed in the global data set. Additionally, the objective response rate (ORR) showed a clinically meaningful and significant improvement (21.5% vs. 8.3%; OR 3.17).

In terms of safety, the profiles for both the lenvatinib and sorafenib groups were consistent with previously reported results; the use of lenvatinib proved to be safe and manageable, with patients demonstrating good tolerability and adherence.