Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2022
Afatinib and Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (ALPHA Study): A Phase II Study with Biomarker Analysis.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03695510 (Afatinib and Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma, A Single-Arm, Phase II Study), which is not on this map. Cited by 44 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Afatinib and Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma, A Single-Arm, Phase II Study (ALPHA Study)
Who cites it
44 citing papers in PubMed, 3 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Immunotherapy plus targeted therapy for recurrent or metastatic head and neck squamous cell carcinoma: an updated meta-analysis and subgroup analysis by target mechanism.Frontiers in oncology · 2026Pooled it
- Gene sequencing applications to combat oral-cavity related disorders: a systematic review with meta-analysis.BMC oral health · 2024Pooled it
- Efficacy of cetuximab plus PD-1 inhibitor differs by HPV status in head and neck squamous cell carcinoma: a systematic review and meta-analysis.Journal for immunotherapy of cancer · 2022Pooled it
- Neoadjuvant chemoimmunotherapy with afatinib for locally advanced head and neck squamous cell carcinoma (neoCHANCE-2): an open-label, single-arm, phase 2 study.Journal for immunotherapy of cancer · 2026Trial
- Neoadjuvant tislelizumab with afatinib for locally advanced head and neck squamous cell carcinoma (neoCHANCE-1): a phase 2 clinical trial.Nature communications · 2025Trial
- Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- EGFR activation disrupts immunotherapy response via SHP2-mediated suppression of tumor-intrinsic response to IFN-γ.The Journal of clinical investigation · 2026Article
- Multi-tyrosine kinase inhibitors: exploring immunomodulatory effects on various immune cell types in cancer.Cancer cell international · 2026Review
- EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- 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
- Precision therapy targeting CAMK2 to overcome resistance to EGFR inhibitors in FAT1 -mutated oral squamous cell carcinoma.Chinese medical journal · 2025Article
- Molecular Crosstalk and Therapeutic Synergy: Tyrosine Kinase Inhibitors and Cannabidiol in Oral Cancer Treatment.Current issues in molecular biology · 2025Review
- Innovative Approaches in Cancer Treatment: Emphasizing the Role of Nanomaterials in Tyrosine Kinase Inhibition.Pharmaceutics · 2025Review
- Immunotherapeutic strategies in head and neck cancer: challenges and opportunities.The Journal of clinical investigation · 2025Review
- Sex differences in prognostic factors and genomic variations in oral squamous cell carcinoma: A 5-year retrospective study.Journal of dental sciences · 2025Article
- Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma.Oncology reports · 2025Article
- VSIG4Journal of experimental & clinical cancer research : CR · 2025Article
- Pathomics-based machine learning model predicts interferon-gamma expression in head and neck squamous cell carcinoma patients.Frontiers in immunology · 2025Article
- Identification of gastric cancer subtypes based on disulfidptosis-related genes: GPC3 as a novel biomarker for prognosis prediction.Discover oncology · 2024Article
- Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeEGFR pathway inhibition may promote anti-programmed cell death protein 1 (PD-1) responses in preclinical models, but how EGFR inhibition affects tumor antigen presentation during anti-PD-1 monotherapy in humans remain unknown. We hypothesized that afatinib, an irreversible EGFR tyrosine kinase inhibitor, would improve outcomes in patients treated with pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) by promoting antigen presentation and immune activation in the tumor microenvironment. PATIENTS AND
methodsThe ALPHA study (NCT03695510) was a single-arm, Phase II study with Simon's 2-stage design. Afatinib and pembrolizumab were administered to patients with platinum-refractory, recurrent, or metastatic HNSCC. The primary endpoint was the objective response rate (ORR). The study applied gene expression analysis using a NanoString PanCancer Immune Profiling Panel and next-generation sequencing using FoundationOne CDx.
resultsFrom January 2019 to March 2020, the study enrolled 29 eligible patients. Common treatment-related adverse events were skin rash (75.9%), diarrhea (58.6%), and paronychia (44.8%). Twelve patients (41.4%) had an objective partial response to treatment. The median progression-free survival was 4.1 months, and the median overall survival was 8.9 months. In a paired tissue analysis, afatinib-pembrolizumab were found to upregulate genes involved in antigen presentation, immune activation, and natural killer cell-mediated cytotoxicity. Unaltered methylthioadenosine phosphorylase and EGFR amplification may predict the clinical response to the therapy.
conclusionsAfatinib may augment pembrolizumab therapy and improve the ORR in patients with HNSCC. Bioinformatics analysis suggested the enhancement of antigen presentation machinery in the tumor microenvironment.
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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.