# Anlotinib Plus Osimertinib in Osimertinib‐Resistant Nonsquamous Nonsmall Cell Lung Cancer With Gradual Progression: A Retrospective Study

## TL;DR

This study shows that combining anlotinib with osimertinib can help patients with lung cancer who have become resistant to osimertinib, offering a manageable safety profile.

## Contribution

The study evaluates the efficacy and safety of anlotinib plus osimertinib in overcoming resistance in nonsquamous nonsmall cell lung cancer patients.

## Key findings

- The combination therapy achieved a median progression-free survival of 10.0 months.
- The disease control rate was 85.7% with manageable treatment-related toxicities.
- Patients had a median progression-free survival of 22.0 months with prior osimertinib treatment.

## Abstract

Previous studies have shown that anlotinib plus third‐generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) overcome acquired resistance to EGFR‐TKIs in patients with advanced EGFR‐mutant nonsmall cell lung cancer (NSCLC). This study aimed to retrospectively evaluate whether anlotinib plus osimertinib overcame acquired resistance in patients with nsq‐NSCLC who gradually progressed after first‐line EGFR‐TKI treatment.

This study included patients with nsq‐NSCLC who developed gradual progression after first‐line osimertinib treatment, underwent an anlotinib plus osimertinib regimen in Tianjin Medical University General Hospital, and had available data from October 8, 2020 to October 14, 2023. Outcomes included the efficacy, assessed by progression‐free survival (PFS), of anlotinib plus osimertinib treatment (PFS1) and prior osimertinib treatment (PFS2), to disease progression, objective response rate (ORR), disease control rate (DCR), and safety as assessed by the incidence of treatment‐related toxicities.

A total of 28 patients with nsq‐NSCLC were included, with a median follow‐up of 12 months (range, 7.8–16.2). Treatment with anlotinib plus osimertinib led to a median PFS1 of 10.0 months (95% confidence interval [CI], 8.4–11.6). With a median follow‐up from prior osimertinib therapy of 31.5 months (range, 20.8–42.2), the median PFS2 was 22.0 months (95% CI, 17.5–26.5). The ORR to combination therapy was 3.6% (95% CI, 0.2–20.2) and the DCR was 85.7% (95% CI, 67.3–96.0). All patients experienced treatment‐related toxicities, with 10.7% showing grade 3, and none were grade ≥ 4.

Anlotinib plus osimertinib exhibited encouraginsg anti‐tumor activity and had a manageable safety profile in patients with nsq‐NSCLC showing gradual progression on osimertinib.

Previous studies have shown that anlotinib plus third‐generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) overcome acquired resistance to EGFR‐TKIs in patients with advanced EGFR‐mutant nonsmall cell lung cancer (NSCLC). This study included patients with nsq‐NSCLC who developed gradual progression after first‐line osimertinib treatment and underwent anlotinib plus osimertinib. A total of 28 patients with nsq‐NSCLC were included, with a median follow‐up of 12 months (range, 7.8–16.2). Treatment with anlotinib plus osimertinib led to a median PFS1 of 10.0 months. With a median follow‐up from prior osimertinib therapy of 31.5 months, the median PFS2 was 22.0 months. The ORR to combination therapy was 3.6% and the DCR was 85.7%. All patients experienced treatment‐related toxicities, with 10.7% showing grade 3 and none were grade ≥ 4. Anlotinib plus osimertinib exhibited encouraging anti‐tumor activity and had a manageable safety profile in patients with nsq‐NSCLC showing gradual progression on osimertinib.