Related Experiment Video
Updated: Jul 2, 2025
Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
Efficacy of immunotherapy in patients with oncogene-driven non-small-cell lung cancer: a systematic review and
Jiayan Chen1, Wanjun Lu2, Mo Chen1
1Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Background:
Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced non-small-cell lung cancer (NSCLC). However, only about 20% of NSCLC patients can benefit from this treatment. At present, whether patients with driving gene-positive NSCLC can benefit from immunotherapy is one of the hot issues. Therefore, we conducted a meta-analysis to evaluate the efficacy of immunotherapy in patients with oncogene-driven NSCLC and concluded the efficacy of altered subtypes.
Methods:
A literature search was performed using PubMed, Web of Science, and Cochrane databases. The primary endpoints included the objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients with oncogene-driven NSCLC.
Results:
In all, 86 studies involving 4524 patients with oncogene-driven NSCLC were included in this meta-analysis. The pooled ORRs in clinical trials treated with monoimmunotherapy of EGFR, ALK, and KRAS alteration were 6%, 0%, and 23%, respectively. In retrospective studies, the pooled ORRs of EGFR, ALK, KRAS, BRAF, MET, HER2, RET, and ROS1 alteration were 8%, 3%, 28%, 24%, 23%, 14%, 7%, and 8%, respectively. Among them, the pooled ORRs of KRAS non-G12C mutation, KRAS G12C mutation, BRAF V600E mutation, BRAF non-V600E mutation, MET-exon 14 skipping, and MET-amplification were 33% 40%, 20%, 34%, 17%, and 60%, respectively. In addition, the pooled mPFS rates of EGFR, KRAS, MET, HER2, and RET alteration were 2.77, 3.24, 2.48, 2.31, and 2.68 months, while the pooled mOS rates of EGFR and KRAS alteration were 9.98 and 12.29 months, respectively. In prospective data concerning EGFR mutation, the pooled ORR and mPFS treated with chemo-immunotherapy (IC) reached 38% and 6.20 months, while 58% and 8.48 months with chemo-immunotherapy plus anti-angiogenesis therapy (ICA). Moreover, the pooled mPFS and mOS of monoimmunotherapy was 2.33 months and 12.43 months.
Conclusions:
EGFR-, ALK-, HER2-, RET-, and ROS1-altered NSCLC patients have poor reactivity to monoimmunotherapy but the efficacy of immune-based combined therapy is significantly improved. KRAS G12C mutation, BRAF non-V600E mutation, and MET amplification have better responses to immunotherapy, and more prospective studies are needed for further research.
Insights
Immunotherapy shows limited efficacy in non-small-cell lung cancer (NSCLC) with EGFR, ALK, HER2, RET, or ROS1 alterations. However, combined therapies and specific mutations like KRAS G12C, BRAF non-V600E, and MET amplification demonstrate improved responses.
Area of Science:
- Oncology
- Immunotherapy
- Genetics
Background:
- Immunotherapy offers improved survival for advanced non-small-cell lung cancer (NSCLC) patients.
- Current immunotherapy benefits only about 20% of NSCLC patients.
- The efficacy of immunotherapy in oncogene-driven NSCLC is a key research area.
Purpose of the Study:
- To evaluate the efficacy of immunotherapy in patients with oncogene-driven NSCLC.
- To determine the effectiveness of immunotherapy across different oncogene-altered NSCLC subtypes.
Main Methods:
- A meta-analysis was conducted.
- Literature search performed across PubMed, Web of Science, and Cochrane databases.
- Primary endpoints included objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS).
Main Results:
- 86 studies with 4524 patients were analyzed.
- Pooled ORRs for monoimmunotherapy varied significantly by alteration (e.g., EGFR 6%, KRAS 23%).
- Specific mutations like KRAS G12C (40% ORR) and MET amplification (60% ORR) showed higher response rates. Chemo-immunotherapy (IC) and chemo-immunotherapy plus anti-angiogenesis (ICA) demonstrated improved ORR and mPFS in EGFR-mutated NSCLC.
Conclusions:
- NSCLC patients with EGFR, ALK, HER2, RET, and ROS1 alterations show poor response to monoimmunotherapy.
- Immune-based combination therapies significantly improve efficacy.
- KRAS G12C, BRAF non-V600E, and MET amplification alterations indicate better immunotherapy response, warranting further investigation.
More Related Videos
07:59Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
09:38Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Related Concept Videos
01:27Tumor Immunotherapy
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...