ArticleNPJ precision oncology2022
Deletions on 9p21 are associated with worse outcomes after anti-PD-1/PD-L1 monotherapy but not chemoimmunotherapy.
Article in NPJ precision oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 22 citations in OpenAlex.
- Innate [European journal of nuclear medicine and molecular imaging · 2025Trial
- MTAP deficiency enhances collective metastasis in non-small cell lung cancer via WNT3A methylation.Oncogene · 2026Article
- MTAP Deficiency as a Metabolic Vulnerability in Cancer: Implications for Synthetic Lethal Therapy.Cancer science · 2026Review
- Presenting features and outcomes to standard systemic therapies in patients with MTAP-deleted advanced non-small cell lung cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- An immunogenomic classification of solid tumours reveals subtype-specific therapeutic vulnerabilities for immunotherapy.EBioMedicine · 2026Article
- Genomics ofJCO precision oncology · 2026Article
- Somatic copy number alterations profiling in non-small cell lung cancer and their correlation with clinical efficacy in first-line treatment.Genome medicine · 2026Article
- Gene amplification in the premalignant stages of non-small cell lung cancer development.Frontiers in oncology · 2026Review
- Emerging Predictive Biomarkers of Immunotherapy Sensitivity in Patients with Non-Small Cell Lung Cancer.ImmunoTargets and therapy · 2026Review
- Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Review
- Tumor aneuploidy as a prognostic and predictive biomarker in immune checkpoint blockade.Nature genetics · 2025Review
- Molecular characterization of metastatic penile squamous cell carcinoma in developing countries and its impact on clinical outcomes: LACOG 2018 translational study.The oncologist · 2025Article
- Genomic and Immune Landscape Comparison of MET Exon 14 Skipping and MET-Amplified Non-small Cell Lung Cancer.Clinical lung cancer · 2024Article
- Methylthioadenosine Phosphorylase Genomic Loss in Advanced Gastrointestinal Cancers.The oncologist · 2024Article
- CDK4/6 Inhibition Sensitizes Intracranial Tumors to PD-1 Blockade in Preclinical Models of Brain Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Loss of chromosome 9p21 is associated with a poor prognosis in adenosquamous carcinoma of the pancreas.Precision clinical medicine · 2023Article
- Impact of Aneuploidy and Chromosome 9p Loss on Tumor Immune Microenvironment and Immune Checkpoint Inhibitor Efficacy in NSCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023Article
- Article
- Development and validation of an integrative pan-solid tumor predictor of PD-1/PD-L1 blockade benefit.Communications medicine · 2023Article
- Therapy sculpts the complex interplay between cancer and the immune system during tumour evolution.Genome medicine · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NCCN guidelines for first-line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC) patients without targetable driver alterations includes either immunotherapy alone or in combination with chemotherapy. In this study, we investigated genomic predictors of survival after immunotherapy to guide this treatment decision. Cox proportional hazards regression was used to identify genomic correlates of survival in a cohort of EGFR/ALK-, non-squamous NSCLC patients treated with first-line pembrolizumab monotherapy (mono-IO) or pembrolizumab in combination with carboplatin/cisplatin and pemetrexed (chemo-IO) within a real-world clinico-genomic database. The effect of deletions on 9p21 was further evaluated in five additional tumor types. Among mono-IO treated non-squamous NSCLC patients, tumors with 9p21.3 gene deletions (CDKN2A, CDKN2B, MTAP) were associated with worse survival compared to the corresponding deletion-negative tumors (CDKN2A deletion HR = 1.8, P = 0.001). However, this association was not observed among chemo-IO treated patients (CDKN2A deletion HR = 1.1, P = 0.4). This finding remained after adjusting for clinical and genomic features including TMB and PD-L1. Deletions at 9p21.3 were not associated with differences in TMB, PD-L1, or tumor inflammation. Due to the high incidence of 9p21.3 deletions across tumor types, we performed a pan-cancer analysis and found CDKN2A deletion-positive tumors had worse survival following first-line immunotherapy treatment in multiple tumor types (HR = 1.4, P < 0.001). These results indicate deletions at 9p21.3 are a putative negative predictor of clinical benefit from first-line immune checkpoint inhibitors and may have utility in choosing between mono-IO vs chemo-IO regimens in NSCLC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.