Efficacy and Safety of Combined Anlotinib and Icotinib in EGFR-Mutant Advanced Non-Squamous NSCLC: Final Analysis of a Prospective Phase II Study

Individuals diagnosed with non-small cell lung cancer (NSCLC) who carry epidermal growth factor receptor (EGFR) mutations together with additional concurrent mutations generally face a worse outlook. This investigation aimed to assess the combination of anlotinib and icotinib as a potential first-line therapy for advanced NSCLC patients with EGFR mutations, regardless of the presence or absence of concomitant mutations. The phase 2, single-arm, multicentre study (ClinicalTrials.gov NCT03736837) took place in five Chinese hospitals from December 2018 through November 2020. Patients with non-squamous NSCLC exhibiting EGFR-sensitising mutations underwent treatment with anlotinib plus icotinib. The main outcome measure was progression-free survival (PFS). Additional outcomes encompassed objective response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse effects. Enrollment included sixty patients, among whom 31 (52%) presented with concurrent mutations and 29 (48%) with pathogenic concurrent mutations. Median follow-up reached 26.9 (range, 15.0–38.9) months. The ORR stood at 68.5% and DCR at 98.2%. Median PFS reached 15.1 (95% CI: 12.6–17.6) months, satisfying the primary objective; median duration of response (DoR) was 13.5 (95% CI: 10.0–17.1) months, while median OS was 30.0 (95% CI: 25.5–34.5) months. For those with pathogenic concurrent mutations, median PFS was 15.6 (95% CI: 12.5–18.7) months and median OS had not been reached (95% CI: 17.46 months to not reached). Every participant experienced treatment-related adverse events (TRAEs), with 26 (43%) encountering grade ≥3 events and 1 (1.7%) facing serious TRAEs. Combining anlotinib with icotinib proved effective and generally well-tolerated when used as first-line therapy in advanced NSCLC cases positive for EGFR mutations, including those with or without additional concurrent mutations.