Introduction

Lenvatinib is a multi‑kinase inhibitor used at varying doses across cancer settings, yet concerns persist regarding its adverse events. More than 50% of patients experience Grade 3 or higher toxicities, necessitating frequent dose modifications. Indian data on lenvatinib’s efficacy, compliance, and side‑effect profile is scarce.

Aim 

To study the efficacy of lenvatinib and its safety and compliance in dedifferentiated thyroid cancers.

Patient Profile

• N=27
• Adult patients of age ≥ 18 years
• Diagnosed with thyroid cancer
• Treated with lenvatinib
• Time period from January 2018 to December 2021

Methods

• Retrospective Trial
• Patients from a prospectively maintained database at the Head and Neck Medical Oncology Unit, Tata Memorial Centre
• Data on baseline characteristics, prior treatments, details of lenvatinib dosing and compliance, adverse events were extracted from electronic medical records.

Study Endpoints

The primary endpoint was progression‑free survival (PFS), defined as time from lenvatinib initiation to progression or death. Overall survival (OS) was measured from treatment start to death.

Results

Table 1. Baseline Characteristics 

Variable	Value (n = 27)
Age (median)	56 (45–61)
Gender	Male 44.4%, Female 55.6%
ECOG PS	0–1: 66.7%, PS2: 14.8%, PS3: 18.5%
Thyroid Status	Hypothyroid 33.3%, Euthyroid 37%, Hyperthyroid 29.6%
Pathology	Papillary 63%, Follicular 37%
Common Metastatic Sites	Lung 66.7%, Bone 44.4%, Liver 18.5%, Brain 7.4%
Prior Therapy	Surgery 70.4%, RAI 48.1%, RT 29.6%, Sorafenib 14.8%

 

Compliance

• Starting doses ranged from 10–24 mg, with a median starting dose of 20 mg. 
• Frequent dose interruptions in 17 patients) and reductions in15 patient were required. 

Table 2. Starting Dose Distribution

Starting Dose	% of patients
24 mg	37.0%
20 mg	14.8%
18 mg	29.6%
14 mg	11.1%
10 mg	7.4%

 

• Final settled doses ranged from 10–24 mg, with 14 mg and 10 mg each in 25.9% of the cohort. 
• Dose interruptions occurred in >60% of patients; toxicity‑driven discontinuation occurred in four patients (14.8%). 

Table 3. Final Dose Distribution

Settled Dose	% of patients
24 mg	14.8%
20 mg	18.5%
18 mg	14.8%
14 mg	25.9%
10 mg	25.9%

 

Adverse Events

• Hypertension, HFS, proteinuria, oral mucositis and fatigue were the most reported events. 
• Grade ≥3 toxicities were common but manageable. 

Table 4. Adverse Events 

Adverse Event (%)	Grade 1	Grade 2	Grade 3	Grade 4	Grade 5
HFS	11.1%	37%	11.1%	0	0
Proteinuria	11.1%	14.8%	14.8%	0	0
Hypertension	33.3%	0	0	0	0
Oral mucositis	22.2%	14.8%	3.7%	0	0
Anaemia	3.7%	11.1%	0	0	0
Transaminitis	7.4%	7.4%	0	0	0
Diarrhoea	14.8%	18.5%	0	0	0
Fatigue	29.6%	22.2%	11.1%	0	0
Myalgia	29.6%	14.8%	0	0	0
Neutropenia	3.7%	0	0	0	0
Thrombocytopenia	7.4%	0	3.7%	0	0
Itching	3.7%	0	0	0	0
Rash	3.7%	0	0	0	0

 

Objective Response Evaluation

Table 5. Response Rates

Response	n (%)
Overall response rate	62.9%
Stable disease (SD)	25.9%
Progressive disease (PD)	11.1%

 

Progression‑Free Survival (PFS) and Overall Survival (OS)

• There were15 progression events reported and the median PFS was 12.2 months.
• Twelve deaths occurred; The median OS was 35.3 months.
• Starting dose had no significant effect on PFS (HR 1.020; p = 0.764) and OS (HR 1.090; p = 0.303).

Figure 1: Progression free survival and overall survival

              

Conclusion

Real‑world use of lenvatinib shows considerable variability in starting dose. Despite this variation, response rates and overall survival remain consistent with findings from the pivotal study.

Reference

ecancer 2023, 17:1500