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A phase 2 study of E7080 in subjects with advanced thyroid cancer

A phase 2 study of E7080 in subjects with advanced thyroid cancer

51

Overall, the median age was 61.0 years (range: 21 to 84 years), and 30 of 51 subjects (58.8%) were female. The median age was 58.0 years (range: 21 to 74 years) in DTC subjects, 58.0 years (range: 41 to 79 years) in MTC subjects, and 65.0 years (range: 36 to 84 years) in ATC subjects. The median weight was 55.45 kg (range: 39.5 to 98.7 kg) overall. The median weight was 57.10 kg (range: 43.9 to 98.7 kg) in DTC subjects, 52.00 kg (range: 39.5 to 77.5 kg) in MTC subjects, and 54.15 kg (range: 39.9 to 85.3 kg) in ATC subjects. All subjects were Asian (Japanese). The baseline ECOG scores were either 0 or 1 in all histologic subtypes except for 2 ATC subjects with a score of 2.

A total of 51 subjects were enrolled into the study (25 with DTC, 9 with MTC, and 17 with ATC). All these 51 subjects received at least one dose of study drug. Of the 51 subjects, 23 discontinued due to the termination of the study after approval of lenvatinib in Japan, 26 discontinued study drug due to disease progression, 1 discontinued study drug due to AEs, and 1 discontinued study drug due to subject choice. All of the 51 subjects were included in the Full Analysis Set and Safety Analysis Set.

All of the 51 subjects (100.0%) experienced at least one TEAE and each of these 51 subjects (100.0%) had at least one TEAE reported as treatment-related by the investigator. Forty two of 51 subjects (82.4%) had at least one CTCAE Grade 3 or 4 TEAE. Overall, the most frequently reported TEAE was hypertension (90.2%, 46/51 subjects), followed by decreased appetite (78.4%, 40/51 subjects), palmar-plantar erythrodysaesthesia syndrome (76.5%, 39/51 subjects), fatigue (72.5%, 37/51 subjects), proteinuria (60.8%, 31/51 subjects), stomatitis (56.9%, 29/51 subjects), diarrhoea (54.9%, 28/51 subjects), nausea (41.2%, 21/51 subjects), and dysphonia (41.2%, 21/51 subjects). The most frequently reported Grade 3 or Grade 4 TEAE was hypertension (43.1%, 22/51 subjects [15 with DTC, 2 with MTC, and 5 with ATC]), followed by decreased appetite (11.8%, 6/51 subjects [1 with DTC, 2 with MTC and 3 with ATC]). Four subjects experienced at least one Grade 4 TEAE (hypocalcaemia, hyponatraemia, laryngeal stenosis, suicide attempt, and thrombocytopenia).

Not applicable

In DTC subjects, 17 of 25 subjects (68.0%) had a BOR of PR and 8 subjects (32.0%) had a BOR of SD. In MTC subjects, 2 of 9 subjects (22.2%) had a BOR of PR and 7 subjects (77.8%) had a BOR of SD. In ATC subjects, 4 of 17 subjects (23.5%) had a BOR of PR, 12 subjects (70.6%) had a BOR of SD, and 1 subject (5.9%) had a BOR of PD. The ORR (CR+PR) based on the investigator assessment was 68.0% in DTC subjects, 22.2% in MTC subjects, and 23.5% in ATC subjects. The DCR (CR+PR+SD) was 100.0% in both DTC and MTC subjects and 94.1% in ATC subjects. The CBR (CR+PR+dSD) was 84.0% in DTC subjects, 77.8% in MTC subjects, and 70.6% in ATC subjects. The median PFS was 25.8 months in DTC subjects, 9.2 months in MTC subjects, and 7.4 months in ATC subjects. The median OS was 31.8 months in DTC subjects, 12.1 months in MTC subjects, and 10.6 months in ATC subjects.

The oral administration of lenvatinib at a starting dose of 24 mg QD achieved an acceptable and manageable safety profile by following prespecified dose reduction or interruption instructions in subjects with advanced thyroid cancer including DTC, MTC, and ATC. There were no toxicities leading to deaths or withdrawal from the study. Efficacy results confirmed the antitumor activity of lenvatinib in all histologic subtypes of advanced thyroid cancer.

Mar. 01, 2017

https://pubmed.ncbi.nlm.nih.gov/28299283/

Yes

https://www.eisai.com/company/business/research/clinical/index.html

Eisai Co., Ltd.

(医療関係者)https://inquiry.eisai.co.jp/webapp/form/17713_hfab_2/index.do(患者様／一般の方)https://inquiry.eisai.co.jp/webapp/form/17713_hfab_1/index.do

Eisai Co., Ltd.

(医療関係者)https://inquiry.eisai.co.jp/webapp/form/17713_hfab_2/index.do(患者様／一般の方)https://inquiry.eisai.co.jp/webapp/form/17713_hfab_1/index.do

completed

Sept. 03, 2012

Interventional

A multicenter, non-randomized, open-label study

treatment purpose

2

1. Histologically or cytologically diagnosed with thyroid cancer
2. ECOG-PS 0-2
3. Adequate laboratory values/organ function tests

1. Brain metastasis
2. Systemic severe infection
3. Significant cardiovascular impairment
4. QTc greater than 480 milliseconds
5. Active hemoptysis
6. Bleeding or thrombotic disorders
7. Having greater than 1+proteinuria on urine dipstick testing will undero 24-hour urine collection for quantitative assessment of proteinuria
8. Gastrointestinal malabsorption or any other condition in the opinion of the investigator that might affect the absorption of E7080
9. Major surgery within 3 weeks before enrollment
10. With co-existing effusion requiring drainage

Both

Thyroid cancer

investigational material(s)
Generic name etc : E7080
INN of investigational material : Lenvatinib
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : 24 mg once daily

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

safety
Adverse events, serious adverse events
Adverse events and serious adverse events will be collected for 2 years from the treatment start.

safety
pharmacokinetics
-

Aug. 01, 2012