Lenvatinib in the Treatment of Recurrent or Metastatic Adenoid Cystic Carcinoma

Adenoid cystic carcinomas are malignant rare tumorsarising mainly from the salivary glands. Their main treatment at an early stage is surgery and adjuvant (postoperative protective) radiotherapy, whereas recurrent or metastatic adenoid cystic carcinomas have a variable clinical course and limited treatment options. Chemotherapy is known to be not very effective against these tumors. Recently, however, oral anticancer agents of the multitargeted tyrosine kinase inhibitor type have shown modest activity, with objective response rates of %0 to %11. One drug investigated for this purpose is lenvatinib.

A smart drug taken orally as a pill, lenvatinib, previously received approvals for thyroid (2015), kidney (2016) and liver cancer (2018), respectively, from the FDA .

Journal of Clinical Oncology published, on 2 April 2019, a single-center study by Tchekmedyian and colleagues, a phase 2 clinical trial, showing that lenvatinib was active in progressive recurrent or metastatic adenoid cystic carcinoma.

Study details

In the study conducted at Memorial Sloan Kettering Cancer Center, 32 patients with recurrent or metastatic adenoid cystic carcinoma were treated with oral lenvatinib at 24 mg daily. Any previous treatment except lenvatinib was allowed.

The primary endpoint was overall response rate. Among 32 patients, a response in 4 or more would make the study positive. Overall, % 78 had adenoid cystic carcinoma in the salivary glands, and % 96.9 had distant metastases.

Findings

• Five patients (% 15.6) had an objective response, and 24 (% 75) had stable disease.
• Median progression-free survival was 17.5 months.
• Overall, 8 patients had progression; 5 withdrew because of side effects.

Side effects

Overall, 23 patients required at least one dose modification (reduction), and of 32 patients, 18 (% 56) discontinued lenvatinib because of drug-related side effects. The most common severe (grade 3 or 4) side effects were hypertension (% 28.1) and oral pain (% 9.4). Grade 4 effects included myocardial infarction (heart attack), posterior reversible encephalopathy syndrome and intracranial (brain) hemorrhage.

Conclusion

This study shows that lenvatinib can produce meaningful responses in patients with recurrent or metastatic adenoid cystic carcinoma and meets its primary endpoint. Side effects are similar to previous studies and require monitoring and treatment.