Efficacy and Safety of Lenvatinib in Patients with Iodine 131-refractory Thyroid Cancer

5 Feb, 21

Introduction

Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor of the VEGFRs 1, 2, and 3, FGFRs 1 through 4, PDGFR a, RET, and KIT signalling networks

Aim

To assess progression-free survival among patients with iodine-131–refractory thyroid cancer who received lenvatinib as compared with those who received placebo

Patient profile

Patients with progressive thyroid cancer that was refractory to iodine-131

Methods

Phase 3, randomized, double-blind, multicentre study

Endpoints

The primary end point was progression-free survival
Secondary end points included the response rate, overall survival, and safety

Results

The baseline characteristics of the patients were similar in the two groups
A progression-free survival benefit associated with lenvatinib was seen in patients with thyroid cancer of all histologic types examined (papillary, poorly differentiated, follicular, and H?rthle-cell)
The 6-month progression-free survival rates were 77.5% in the lenvatinib group and 25.4% in the placebo group

Figure 1: Progression free survival in lenvatinib group and placebo group

Secondary Endpoints

Lenvatinib was associated with significant improvement in the response rate
The response rate was 64.8% in the lenvatinib group (4 complete responses and 165 partial responses) and 1.5% in the placebo group (P<0.001)
The median overall survival was not reached in either group
- The difference in overall survival between the groups was not significant

Table 1: Secondary efficacy endpoints

Outcome	Lenvatinib (N = 261)	Placebo (N = 131)	Odds Ratio
Overall survival
Median— mo	NE (22.0–NE)	NE (14.3–NE)
Rate, — %
6 mo	90.7	85.3
12 mo	81.6	70.0
18 mo	72.3	63.0
24 mo	58.2	NE
Response rate — no. (%) **	64.8	1.5	28.87
Complete response	1.5	0
Partial response	63.2	1.5
Stable disease	23.0	54.2
Durable stable disease ≥23 wk	15.3	29.8
Progressive disease	6.9	39.7
Could not be evaluated	5.4	4.6
Exploratory efficacy end points
Disease-control rate — no. (%) ††	87.7	55.7	5.05
Clinical-benefit rate — no. (%)	80.1	31.3	7.63
Time to first objective response — mo
Median	2.0	5.6

NE not estimable

** Tumour responses were assessed with the use of Response Criteria in Solid Tumours (RECIST), version 1.1, and were confirmed by independent centralized radiologic review

†† The disease-control rate was calculated as complete response plus partial response plus stable disease

§§ The clinical-benefit rate was calculated as complete response plus partial response plus durable stable disease

Safety

Toxic effects of therapy were considerable, and most toxic effects were managed with dose modification and medical therapy

Figure 2: Safety and Side Effect Profile

Conclusion

The study demonstrated that compared to placebo, lenvatinib was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131– refractory thyroid cancer.
Patients who received lenvatinib had more adverse effects.

Reference

N Engl J Med 2015; 372:621-30.