ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Phase I Clinical Trial of Combination Propranolol and Pembrolizumab in Locally Advanced and Metastatic Melanoma: Safety, Tolerability, and Preliminary Evidence of Antitumor Activity.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- The Efficacy and Safety of Beta-blockers and Immune Checkpoint Inhibitors in Patients with Cancer: A Systematic Review and Meta-analysis.Targeted oncology · 2025Pooled it
- Phase II study of propranolol feasibility with neoadjuvant chemotherapy in patients with newly diagnosed breast cancer.Breast cancer research and treatment · 2021Trial
- Review
- Chronic stress and myeloid immunosuppression in cancer: A neuroimmune link to behavioral dysfunction.Brain, behavior, & immunity - health · 2026Review
- Neuromedin U 'innervation' reprograms myeloid immunosuppression in neuroendocrine prostate cancer.Oncogene · 2026Article
- Neural-tumor interactions: bidirectional regulatory mechanisms and nervous system-targeted tumor therapeutic strategies.Biomarker research · 2026Review
- Cancer Neuroscience: From Local Neuro-Immune Microenvironments to Systemic Brain-Body Circuitry.MedComm · 2026Review
- Electroacupuncture enhances CD8+ T cells recruitmentmodulating sympathetic nervous system to suppress tumor growth in mice bearing triple-negative breast cancer.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Neural regulation of tumor immunity: emerging opportunities to enhance cancer immunotherapy.Experimental & molecular medicine · 2026Review
- Neuro-immune crosstalk in the tumor microenvironment: mechanisms and therapeutic implications for cancer immunotherapy.Journal of neuroinflammation · 2026Review
- β-Adrenergic receptors as immunomodulators in T cells: mechanisms of neuroimmune crosstalk and pathophysiological implications.Molecular medicine (Cambridge, Mass.) · 2026Review
- The neuroimmune axis in breast cancer: from mechanistic insights to clinical applications.BMC medicine · 2026Review
- The Neuroimmune Connectome: Understanding how the Peripheral Nervous System shapes Immunity.ImmunoHorizons · 2026Review
- Obesity and Cancer: From Systemic Metabolic Reprogramming to Immunotherapy Paradox.Metabolites · 2026Review
- Article
- Nervous and immune system crosstalk shapes cancer progression and treatment response.Discover oncology · 2026Review
- The impact of concomitant medications on treatment outcomes in patients with cancer receiving immune checkpoint inhibitors.Nature reviews. Cancer · 2026Review
- Lessons from neoadjuvant immunotherapy in melanoma: understanding antitumour immunity and tumour escape.Nature reviews. Immunology · 2026Review
- Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 1 country.
Funding
Abstract
purposeIncreased β-adrenergic receptor (β-AR) signaling has been shown to promote the creation of an immunosuppressive tumor microenvironment (TME). Preclinical studies have shown that abrogation of this signaling pathway, particularly β2-AR, provides a more favorable TME that enhances the activity of anti-PD-1 checkpoint inhibitors. We hypothesize that blocking stress-related immunosuppressive pathways would improve tumor response to immune checkpoint inhibitors in patients. Here, we report the results of dose escalation of a nonselective β-blocker (propranolol) with pembrolizumab in patients with metastatic melanoma. PATIENTS AND
methodsA 3 + 3 dose escalation study for propranolol twice a day with pembrolizumab (200 mg every 3 weeks) was completed. The primary objective was to determine the recommended phase II dose (RP2D). Additional objectives included safety, antitumor activity, and biomarker analyses. Responders were defined as patients with complete or partial response per immune-modified RECIST at 6 months.
resultsNine patients with metastatic melanoma received increasing doses of propranolol in cohorts of 10, 20, and 30 mg twice a day. No dose-limiting toxicities were observed. Most common treatment-related adverse events (TRAEs) were rash, fatigue, and vitiligo, observed in 44% patients. One patient developed two grade ≥3 TRAEs. Objective response rate was 78%. While no significant changes in treatment-associated biomarkers were observed, an increase in IFNγ and a decrease in IL6 was noted in responders.
conclusionsCombination of propranolol with pembrolizumab in treatment-naïve metastatic melanoma is safe and shows very promising activity. Propranolol 30 mg twice a day was selected as RP2D in addition to pembrolizumab based on safety, tolerability, and preliminary antitumor activity.
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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.