Update From ALTER-L004: First-Line Anlotinib Plus Icotinib in EGFR-Mutated NSCLC

By: Julia Fiederlein
Posted: Thursday, February 3, 2022

In the ALTER-L004 trial, the oral multikinase inhibitor anlotinib plus the oral EGFR tyrosine kinase inhibitor icotinib demonstrated “encouraging” efficacy in patients with untreated, EGFR-mutated advanced non–small cell lung cancer (NSCLC). The updated results, which were presented by Dingzhi Huang, MD, of the Tianjin Medical University Cancer Institute and Hospital, China, and colleagues during the European Society for Medical Oncology (ESMO) Congress 2021 (Abstract 1219P) and published in the Annals of Oncology, further supported these findings.

“[Anlotinib plus icotinib] may represent a new treatment option for patients with concomitant mutations,” the investigators commented. “The combination was well tolerated, and the adverse events were manageable.”

A total of 56 patients with locally advanced and/or metastatic stage IIIb to IV nonsquamous NSCLC who were treated with anlotinib plus icotinib underwent at least one tumor assessment. The median duration of progression-free survival was 15.1 months. The disease control and objective response rates were 98.2% and 67.9%, respectively. By the first evaluation, more than half of the patients (58.9%) experienced a reduction in tumor size of at least 30%; this defined early tumor shrinkage. The median duration of progression-free survival was 15.6 months in patients with concomitant mutations and 14.9 months in those with pathogenic concomitant mutations. Patients with concomitant or pathogenic concomitant mutations achieved rates of objective response, disease control, and early tumor shrinkage of more than 80%, 100%, and 70%, respectively.

Adverse events were reported in 100% of patients, and the incidence rate of grade 3 or 4 adverse events was 40%. Hypertriglyceridemia, diarrhea, hypercholesterolemia, hypertension, rash, proteinuria, hand and foot skin reaction, increased alanine aminotransferase, hypothyroidism, increased thyroid-stimulating hormone, increased aspartate aminotransferase, and urine occult blood were among the most frequently reported adverse events. The most common grade 3 or 4 adverse events were hypertension and diarrhea. The investigators reported one drug-related serious adverse event due to acute coronary syndrome. A total of 26.7% of patients had to adjust the treatment dosage.

Disclosure: The study authors reported no conflicts of interest.

Annals of Oncology

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