# The efficacy and safety of radiotherapy and immunotherapy with or without anlotinib in driver gene-negative advanced non-small cell lung cancer

**Authors:** Weijian Miao, Jingjing Sun, QiMeng Tao, Yan Zhou, Hao Jiang

PMC · DOI: 10.3389/fonc.2026.1694207 · Frontiers in Oncology · 2026-02-09

## TL;DR

Adding anlotinib to radiotherapy and immunotherapy improved progression-free survival in some lung cancer patients, but did not increase overall survival and caused more side effects.

## Contribution

This study evaluates the impact of adding anlotinib to radiotherapy and immunotherapy in advanced non-small cell lung cancer patients.

## Key findings

- Anlotinib addition improved progression-free survival (10.0 vs 6.0 months) but not overall survival.
- The triple therapy showed a 10% higher objective response rate compared to dual therapy.
- Toxic effects were more frequent with the triple regimen but remained manageable.

## Abstract

Radiotherapy paired with immune checkpoint inhibitors (ICIs) has benefited patients with driver gene-negative NSCLC, although treatment resistance remains an obstacle. Anlotinib, a broad-spectrum tyrosine kinase inhibitor, has potential to reinforce immunotherapy by modifying the tumor environment. This study investigates whether incorporating anlotinib can amplify the efficacy of combined treatment protocols.

A total of 203 individuals diagnosed with stage IIIB-IV NSCLC were retrospectively assessed. Treatment occurred at the First Affiliated Hospital of Bengbu Medical University between 2021 and 2023. Patients were grouped into those receiving radiotherapy and immunotherapy (n=123) and those receiving anlotinib in addition (n=80). Clinical outcomes assessed included PFS, OS, response metrics, and treatment-related side effects.

Over a median follow-up of 26 months, the group receiving anlotinib showed enhanced median PFS (10.0 months vs 6.0 months, P = 0.043 HR: 0.708, 95% CI: 0.496–1.009). However, there was no statistically significant difference in overall survival (OS) between the two groups (median OS: 20.0 vs. 18.0 months; P = 0.344, HR:0.848 95% CI:0.597-1.205). the RT+IO+A regimen demonstrated a 10% higher ORR than the RT+IO regimen (45.0% vs. 35.0%), while the DCR was similar between the two groups (88.8% vs. 91.1%). Toxic effects were manageable but more frequent in the triple-therapy group.

The triple regimen improved disease stabilization but did not yield OS benefits. Due to the increased toxicity associated with the addition of anlotinib, Future research is required to weigh advantages against added toxicity.

## Linked entities

- **Chemicals:** anlotinib (PubChem CID 25017411)
- **Diseases:** non-small cell lung cancer (MONDO:0005233), NSCLC (MONDO:0005233)

## Full-text entities

- **Genes:** CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, ALK (ALK receptor tyrosine kinase) [NCBI Gene 238] {aka ALK1, CD246, NBLST3}, FGFR1 (fibroblast growth factor receptor 1) [NCBI Gene 2260] {aka BFGFR, CD331, CEK, ECCL, FGFBR, FGFR-1}, ROS1 (ROS proto-oncogene 1, receptor tyrosine kinase) [NCBI Gene 6098] {aka MCF3, ROS, c-ros-1}, KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}, PDGFRB (platelet derived growth factor receptor beta) [NCBI Gene 5159] {aka CD140B, IBGC4, IMF1, JTK12, KOGS, OPDKD}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}
- **Diseases:** hypertension (MESH:D006973), Hematological toxicity (MESH:D006402), death (MESH:D003643), neutropenia (MESH:D009503), bone metastasis (MESH:D009362), anemia (MESH:D000740), bone (MESH:D001847), Toxic effects (MESH:D064420), Gastrointestinal toxicity (MESH:D005767), thrombocytopenia (MESH:D013921), stage III disease (MESH:D007676), foot reactions (MESH:D005530), infections (MESH:D007239), liver dysfunction (MESH:D017093), PD (MESH:D018450), IV (MESH:D006011), thyroid dysfunction (MESH:D013959), M (MESH:C566367), nausea/vomiting (MESH:D020250), glioblastoma (MESH:D005909), ECOG-PS (MESH:D000072716), stage IVA/IVB disease (MESH:C538167), dyslipidemia (MESH:D050171), small-cell lung cancer (MESH:D055752), anorexia (MESH:D000855), radiation pneumonitis (MESH:D017564), hand foot skin reactions (MESH:D060831), lung lesion (MESH:D008171), Cancer (MESH:D009369), Lung cancer (MESH:D008175), diarrhea (MESH:D003967), stage IIIB- (MESH:C566890), pneumonia (MESH:D011014), III disease (MESH:D015840), fatigue (MESH:D005221), IV disease (MESH:D020432), autoimmune diseases (MESH:D001327), organ dysfunction (MESH:D009102), bleeding (MESH:D006470), rash (MESH:D005076), leukopenia (MESH:D007970), hypoxia (MESH:D000860), esophagitis (MESH:D004941), squamous cell carcinoma (MESH:D002294), NSCLC (MESH:D002289), itching (MESH:D011537), proteinuria (MESH:D011507), M1 (MESH:D015470)
- **Chemicals:** ALTER-L001 (-), camrelizumab (MESH:C000631724), durvalumab (MESH:C000613593), sintilimab (MESH:C000632826), docetaxel (MESH:D000077143), Anlotinib (MESH:C000625192), platinum (MESH:D010984), bilirubin (MESH:D001663), tislelizumab (MESH:C000707970)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12926104/full.md

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Source: https://tomesphere.com/paper/PMC12926104