ArticleNature communications2020
PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02027961 (A Phase 1 Open-label Study of Safety and Tolerability of MEDI4736 in Subjects With Metastatic or Unresectable Melanoma in Combination With Dabrafenib and Trametinib or With Trametinib Alone), which is not on this map. Cited by 53 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Phase 1 Open-label Study of Safety and Tolerability of MEDI4736 in Subjects With Metastatic or Unresectable Melanoma in Combination With Dabrafenib and Trametinib or With Trametinib Alone
Who cites it
53 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Pooled it
- Efficacy and safety of PD-1 and PD-L1 inhibitors combined with chemotherapy in randomized clinical trials among triple-negative breast cancer.Frontiers in pharmacology · 2022Pooled it
- Triple Combination Therapy With PD-1/PD-L1, BRAF, and MEK Inhibitor for Stage III-IV Melanoma: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- COMBI-I: Long-Term Overall Survival With Spartalizumab Plus Dabrafenib and Trametinib inJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Trial
- Combined MEK/PD-L1 Inhibition Alters Peripheral Cytokines and Lymphocyte Populations Correlating with Improved Clinical Outcomes in Advanced Biliary Tract Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Deciphering protein mutation-phenotype linkages from CRISPR-based tiling mutagenesis screens.Cell systems · 2026Article
- Targeting the noncanonical function of metabolic enzyme PHGDH in driving PD-L1 expression and cancer immune evasion.Cell reports. Medicine · 2026Article
- Single-cell-based identification of drug synergy with immunotherapy via tumor microenvironment remodeling.Journal for immunotherapy of cancer · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Collagen-mediated pro-tumorigenic MAPK activation drives stromal-immune reprogramming in solid cancers.Frontiers in immunology · 2026Article
- Gut microbiota affects PD-L1 therapy and its mechanism in melanoma.Cancer immunology, immunotherapy : CII · 2025Review
- Resistance mechanisms to immune checkpoint inhibitors: updated insights.Molecular cancer · 2025Review
- Combinational therapeutic strategies to overcome resistance to immune checkpoint inhibitors.Frontiers in immunology · 2025Review
- Observational
- Inflammatory signaling in targeted therapy resistance: focus on EGFR-targeted treatment.Cancer biology & medicine · 2024Article
- Genomic and molecular alterations associated with primary resistance to immune checkpoint inhibitors.Cancer immunology, immunotherapy : CII · 2024Review
- Preclinical evidence for employing MEK inhibition in NRAS mutated pediatric gastroenteropancreatic neuroendocrine-like tumors.Translational oncology · 2024Article
- PIKfyve controls dendritic cell function and tumor immunity.bioRxiv : the preprint server for biology · 2024Article
- PIKfyve, expressed by CD11c-positive cells, controls tumor immunity.Nature communications · 2024Article
- Beyond the Barrier: Unraveling the Mechanisms of Immunotherapy Resistance.Annual review of immunology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors.
Funding
Abstract
Combining PD-L1 blockade with inhibition of oncogenic mitogen-activated protein kinase (MAPK) signaling may result in long-lasting responses in patients with advanced melanoma. This phase 1, open-label, dose-escalation and -expansion study (NCT02027961) investigated safety, tolerability and preliminary efficacy of durvalumab (anti-PD-L1) combined with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) for patients with BRAF-mutated melanoma (cohort A, n = 26), or durvalumab and trametinib given concomitantly (cohort B, n = 20) or sequentially (cohort C, n = 22) for patients with BRAF-wild type melanoma. Adverse events and treatment discontinuation rates were more common than previously reported for these agents given as monotherapy. Objective responses were observed in 69.2% (cohort A), 20.0% (cohort B) and 31.8% (cohort C) of patients, with evidence of improved tumor immune infiltration and durable responses in a subset of patients with available biopsy samples. In conclusion, combined MAPK inhibition and anti-PD-L1 therapy may provide treatment options for patients with advanced melanoma.
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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 Socratic graph.