Lenvatinib 10mg is suitable for the treatment of hepatocellular carcinoma, renal cell carcinoma, differentiated cancer, and endometrial cancer.

Lenvatinib instructions

Product Name: LuciLenva

Manufacturer: Lucius Pharmaceuticals

Chinese name: Lenvatinib

English Name: Lenvatinib

Drug approval number: 03 L 1080/24

 

 

【Summary】

Lenvatinib is a multi-target inhibitor, including 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 cancer (DTC): used to treat patients with locally recurrent or metastatic, progressive, and radioactive iodine-refractory differentiated cancer (DTC).

2. Renal cell carcinoma: In combination with pembrolizumab, it is used for adult patients with advanced renal cell carcinoma (RCC). In combination with everolimus, it is used to treat adult patients with advanced renal cell carcinoma (RCC) who have received one anti-angiogenic therapy.

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

4. Endometrial cancer (EC): Used in combination with pembrolizumab to treat patients with advanced endometrial cancer (EC).

 

【Specification】

10mg/capsule 30 capsules/box

 

【Storage】

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

 

【Usage and Dosage】

1. Single-dose treatment:

1. DTC: The recommended dose is 24 mg, taken orally once a day.

2. HCC: The recommended dose is based on actual body weight: patients weighing 60 kg or more take 12 mg orally per day, and patients weighing less than 60 kg take 8 mg orally per day.

2. Combined therapy:

1. EC: The recommended dose is 20 mg once daily, used in combination with 200 mg pembrolizumab.

2. RCC: recommended dose:

①. Used in combination with pembrolizumab, take orally once a day, 20 mg each time.

②. Used in combination with everolimus, take orally once a day, 18 mg each time.

 

【Adverse Reactions】
The most common adverse reactions to lenvatinib (incidence greater than or equal to 30%) are hypertension, fatigue, diarrhea, arthralgia and myalgia, decreased appetite, weight loss, nausea, stomatitis, headache, vomiting, proteinuria, and hand-foot syndrome dysphonia.

 

【Warnings and Precautions】

1. Hypertension:

Treatment is required to control blood pressure. Grade 3 hypertension requires optimal antihypertensive treatment. If life-threatening hypertension occurs, medication should be discontinued.

2. Heart failure:

Monitor for clinical symptoms or signs of cardiac decompensation. Grade 3 cardiac insufficiency requires cautious use of medication, and grade 4 cardiac insufficiency requires discontinuation of medication.

3. Arterial thrombotic events:

If arterial thromboembolic events are detected, please discontinue the drug.

4. Hepatotoxicity:

Monitor liver function before starting lenvatinib and regularly throughout treatment. Use with caution in patients with grade 3 or higher liver impairment and discontinue the drug in patients with liver failure.

5. Proteinuria

Monitor proteinuria before starting lenvatinib and periodically throughout. If proteinuria is ≥ 2 g in 24 hours, the dose should be reduced and nephrotic syndrome should be discontinued.

6. Diarrhea:

May be severe and recurrent. Use standard anti-diarrhea therapy. Reduce dose for grade 3 diarrhea and discontinue for grade 4 diarrhea.

7. Renal failure and impairment:

Withhold the drug for Grade 3 or 4 renal failure.

8. Gastrointestinal perforation and fistula formation:

Discontinue medication in patients who develop gastrointestinal perforation or life-threatening fistula.

9. QT interval prolongation:

Monitor and correct electrolyte abnormalities. Use with caution for Grade 3 or higher QT prolongation.

10. Hypocalcemia:

Monitor blood calcium levels and supplement calcium at least monthly and replace if necessary.

11. Reversible posterior leukoencephalopathy syndrome (RPLS):

Discontinue use until fully resolved.

12. Bleeding events:

For grade 3 bleeding, the medication should be suspended; for grade 4 bleeding, the medication should be discontinued.

13. Thyroid stimulating hormone suppresses thyroid dysfunction:

Monitor TSH levels, monthly monitoring and use of thyroid replacement medication as needed.

14. Embryo-fetal toxicity:

May cause fetal harm. Inform the potential risks and use effective contraceptive measures. If taking during breastfeeding, discontinue breastfeeding.

 

【Clinical Data】

1. Lenvatinib Thyroid Cancer Data

1) The median progression-free survival (mPFS) in the lenvatinib group was 18.3 months vs 3.6 months in the placebo group;

2) The objective response rate in the lenvatinib group was 64.8% VS 1.5% in the placebo group.

2. Lenvatinib renal cancer data

1) The median progression-free survival (mPFS) of the lenvatinib + everolimus combination group was 14.6 months vs 5.5 months of the everolimus monotherapy group;

2) The overall survival (OS) of the lenvatinib + everolimus combination group was 25.5 months vs 15.4 months of the everolimus monotherapy group;

3) The objective response rate of the lenvatinib + everolimus combination group was 37% VS 6% of the everolimus monotherapy group.

3. Lenvatinib liver cancer data

The results of the randomized, open, non-inferiority Phase III clinical trial (REFLECT) of lenvatinib as a first-line treatment for uHCC were announced for the first time at the American Society of Oncology (ASCO) annual meeting in Chicago on June 4, 2017.

A total of 954 patients with previously untreated uHCC (≥ 1 measurable target lesion, Barcelona stage B or C, Child-Pugh A, ECOG PS ≤ 1) were enrolled in the study and randomly assigned to the lenvatinib group (478 patients, body weight ≥ 60 kg: 12 mg qd; body weight < 60 kg: 8 mg qd) or the sorafenib group (476 patients, 400 mg bid).

In terms of OS, lenvatinib was non-inferior to sorafenib, with median OS of 13.6 months and 12.3 months, respectively. Subgroup analysis showed that first-line lenvatinib treatment had better OS benefit than sorafenib treatment in the Asia-Pacific population.

As first-line treatment options for uHCC, there were statistically and clinically significant differences in PFS, TTP, and ORR between lenvatinib and sorafenib. The median PFS in the lenvatinib group was twice 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 (median time to disease progression) was more than twice that of sorafenib (8.9 months vs. 3.7 months, p< 0.00001).

In terms of safety, the number of patients experiencing treatment-related adverse events (TEAEs) in the two groups was similar. Most TEAEs of lenvatinib were hypertension (42%), diarrhea (39%), decreased appetite (34%), weight loss (31%) and fatigue (30%), which were similar to previously reported adverse events of lenvatinib.

The median treatment duration for lenvatinib and sorafenib was 5.7 and 3.7 months, respectively. 13% and 9% of patients in the two groups discontinued treatment due to adverse reactions, and 33% and 39% of patients received second-line treatment, respectively.

4. Lenvatinib liver cancer Chinese subgroup data

The REFELECT study is a global, multicenter, randomized, open-label, non-inferiority Phase III clinical trial that enrolled 954 previously untreated patients with unresectable HCC, including nearly 300 patients from China (mainland, Taiwan Province, and Hong Kong Special Administrative Region). It aims to evaluate the efficacy and safety of first-line lenvatinib (lenvatinib is translated as lenvatinib in China, the same as lenvatinib above) and the current standard of treatment sorafenib.

Subgroup analysis of Chinese patients showed that compared with the median OS of 10.2 months in the sorafenib group, the lenvatinib group significantly prolonged the patients' median OS to 15.0 months, while significantly reducing the risk of death by 27% (HR 0.73).

In terms of secondary endpoints, compared with the sorafenib group, the 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) of patients in the lenvatinib group were significantly prolonged, which was more advantageous than the global data; the objective response rate (ORR) also achieved clinically significant improvement (21.5% vs 8.3%, OR 3.17).

In terms of safety, both the lenvatinib group and the sorafenib group were consistent with previously reported results. The use of lenvatinib was safe and controllable, and patients had good tolerance and compliance.