Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2022
Tadalafil Enhances Immune Signatures in Response to Neoadjuvant Nivolumab in Resectable Head and Neck Squamous Cell Carcinoma.
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 NCT03238365 (Window of Opportunity Trial of Nivolumab and Tadalafil in Patients With Squamous Cell Carcinoma of the Head and Neck), which is not on this map. Cited by 36 papers, 1 of them a synthesis 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.
Window of Opportunity Trial of Nivolumab and Tadalafil in Patients With Squamous Cell Carcinoma of the Head and Neck
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- A systematic review of neoadjuvant and definitive immunotherapy in locally advanced head and neck squamous cell carcinoma.Cancer medicine · 2023Pooled it
- Pre-existing systemic immune state and dynamic myeloid remodeling shape response to neoadjuvant PD-L1 blockade.Journal for immunotherapy of cancer · 2026Trial
- Extracellular Matrix-MYCAF Signatures Correlate with Resistance to Neoadjuvant aPD-L1 Immune Checkpoint Inhibition with Durvalumab + Metformin in HPV+ HNSCC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Response-Adaptive Surgical Timing in Neoadjuvant Immunotherapy Demonstrates Enhanced Pathologic Treatment Response in Head and Neck Squamous Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Assessment methods of pathological complete response in neoadjuvant head and neck cancer clinical trials: a scoping review.The journal of pathology. Clinical research · 2026Article
- Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor of Survival Outcomes in Head and Neck Squamous Cell Carcinoma Receiving Neoadjuvant Immunotherapy.Cancer medicine · 2026Article
- Targeting inflammatory microenvironments: overcoming therapy resistance and immunosuppression.Molecular cancer · 2026Review
- Immunotherapy in Head and Neck Cancer-Where Are We Now and Where Are We Headed?International journal of molecular sciences · 2026Review
- Evaluation of neoadjuvant immunotherapy regimens for head and neck squamous cell carcinoma: a systematic review and single-arm and network meta-analysis.International journal of surgery (London, England) · 2026Article
- Cationic nanoparticles with disrupting neutrophil extracellular traps inhibit the progression of head and neck squamous cell carcinoma.Frontiers in cell and developmental biology · 2026Article
- Modulating phosphodiesterase-5 activity to suppress the immunosuppressive mechanisms of myeloid-derived suppressor cells in breast cancer.Breast cancer research : BCR · 2025Article
- Article
- Tumor microenvironment governs the prognostic landscape of immunotherapy for head and neck squamous cell carcinoma: A computational model-guided analysis.PLoS computational biology · 2025Article
- T cell dynamics with neoadjuvant immunotherapy in head and neck cancer.Nature reviews. Clinical oncology · 2025Review
- Oncologic outcomes following neoadjuvant immunochemotherapy in locally advanced oral squamous cell carcinoma.Frontiers in immunology · 2025Article
- Evaluation of ctDNA-guided adjuvant therapy de-escalation in head and neck squamous cell carcinoma: a comparative cohort study.Frontiers in immunology · 2025Article
- Improved survival with phosphodiesterase-5 inhibitor use in men with male-predominant cancers: real-world large database study.Frontiers in oncology · 2025Article
- Effective imaging examination evaluation method for surgical pathological complete responds of head and neck squamous cell carcinoma after neoadjuvant immunochemotherapy.Frontiers in oncology · 2025Article
- Platelet signaling in immune landscape: comprehensive mechanism and clinical therapy.Biomarker research · 2024Review
- MDSC: a new potential breakthrough in CAR-T therapy for solid tumors.Cell communication and signaling : CCS · 2024Review
Corrections and comments
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Authors and funding
28 authors at 5 institutions in 1 country.
Funding
Abstract
purposeWe hypothesize that the addition of the phosphodiesterase-5 inhibitor tadalafil to the PD-1 inhibitor nivolumab, is safe and will augment immune-mediated antitumor responses in previously untreated squamous cell carcinoma of the head and neck (HNSCC). PATIENTS AND
methodsWe conducted a two-arm multi-institutional neoadjuvant randomized trial in any-stage resectable HNSCC (NCT03238365). Patients were stratified at randomization by human papillomavirus (HPV) status. Patients in both arms received nivolumab 240 mg intravenously on days 1 and 15 followed by surgery on day 28. Those in the combination therapy arm also received tadalafil 10 mg orally once daily for 4 weeks. Imaging, blood, and tumor were obtained pretreatment and posttreatment for correlative analysis.
resultsNeoadjuvant therapy was well-tolerated with no grade 3 to 5 adverse events and no surgical delays. Twenty-five of 46 (54%) evaluable patients had a pathologic treatment response of ≥20%, including three (7%) patients with a complete pathologic response. Regardless of HPV status, tumor proliferation rate was a negative predictor of response. A strong pretreatment T-cell signature in the HPV-negative cohort was a predictor of response. Tadalafil altered the immune microenvironment, as evidenced by transcriptome data identifying enriched B- and natural killer cell gene sets in the tumor and augmented effector T cells in the periphery.
conclusionsPreoperative nivolumab ± tadalafil is safe in HNSCC and results in more than 50% of the patients having a pathologic treatment response of at least 20% after 4 weeks of treatment. Pretreatment specimens identified HPV status-dependent signatures that predicted response to immunotherapy while posttreatment specimens showed augmentation of the immune microenvironment with the addition of tadalafil.
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What OpenQuestion holds
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.