Trial reportRetina (Philadelphia, Pa.)2019
FREQUENT SUBCLINICAL MACULAR CHANGES IN COMBINED BRAF/MEK INHIBITION WITH HIGH-DOSE HYDROXYCHLOROQUINE AS TREATMENT FOR ADVANCED METASTATIC BRAF MUTANT MELANOMA: Preliminary Results From a Phase I/II Clinical Treatment Trial.
Trial report in Retina (Philadelphia, Pa.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- BAMM (BRAF Autophagy and MEK Inhibition in Melanoma): A Phase I/II Trial of Dabrafenib, Trametinib, and Hydroxychloroquine in Advanced BRAFV600-mutant Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study.The Lancet. Oncology · 2020Trial
- Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.JAMA network open · 2020Trial
- Optical Coherence Tomography and Angiography in Hydroxychloroquine Retinopathy: A Narrative Review.Diagnostics (Basel, Switzerland) · 2026Review
- Tasurgratinib in patients with cholangiocarcinoma or gastric cancer: Expansion part of the first-in-human phase I study.Cancer science · 2025Article
- Article
- Review
- Clinical experience with pemigatinib for previously treated metastatic cholangiocarcinoma: practical considerations from clinical cases.Drugs in context · 2023Article
- Molecular Pathways and Mechanisms of BRAF in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Review
- Short-term Assessment of Subfoveal Injection of Adeno-Associated Virus-Mediated hCHM Gene Augmentation in Choroideremia Using Adaptive Optics Ophthalmoscopy.JAMA ophthalmology · 2022Article
- Bardet-Biedl syndrome-7 (Ophthalmic genetics · 2021Article
- Visible Light Optical Coherence Tomography (OCT) Quantifies Subcellular Contributions to Outer Retinal Band 4.Translational vision science & technology · 2021Article
- DCZ5248, a novel dual inhibitor of Hsp90 and autophagy, exerts antitumor activity against colon cancer.Acta pharmacologica Sinica · 2021Article
- [Toxic retinopathies].Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft · 2020Article
- Spectral-Domain Optical Coherence Tomography Is More Sensitive for Hydroxychloroquine-Related Structural Abnormalities Than Short-Wavelength and Near-Infrared Autofluorescence.Translational vision science & technology · 2020Article
- Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology.Nature reviews. Rheumatology · 2020Review
- Safety of Same-Eye Subretinal Sequential Readministration ofMolecular therapy. Methods & clinical development · 2019Article
- The multifaceted role of autophagy in cancer and the microenvironment.Medicinal research reviews · 2019Review
- Reversible Retinopathy Associated with Fibroblast Growth Factor Receptor Inhibitor.Case reports in ophthalmologyArticle
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo assess the potential ocular toxicity of a combined BRAF inhibition (BRAFi) + MEK inhibition (MEKi) + hydroxychloroquine (HCQ) regime used to treat metastatic BRAF mutant melanoma.
methodsPatients with stage IV metastatic melanoma and BRAF V600E mutations (n = 11, 31-68 years of age) were included. Treatment was with oral dabrafenib, 150 mg bid, trametinib, 2 mg/day, and HCQ, 400 mg to 600 mg bid. An ophthalmic examination, spectral domain optical coherence tomography, near-infrared and short-wavelength fundus autofluorescence, and static perimetry were performed at baseline, 1 month, and q/6 months after treatment.
resultsThere were no clinically significant ocular events; there was no ocular inflammation. The only medication-related change was a separation of the photoreceptor outer segment tip from the apical retinal pigment epithelium that could be traced from the fovea to the perifoveal retina noted in 9/11 (82%) of the patients. There were no changes in retinal pigment epithelium melanization or lipofuscin content by near-infrared fundus autofluorescence and short-wavelength fundus autofluorescence, respectively. There were no inner retinal or outer nuclear layer changes. Visual acuities and sensitivities were unchanged.
conclusionBRAFi (trametinib) + MEKi (dabrafenib) + HCQ causes very frequent, subclinical separation of the photoreceptor outer segment from the apical retinal pigment epithelium without inner retinal changes or signs of inflammation. The changes suggest interference with the maintenance of the outer retinal barrier and/or phagocytic/pump functions of the retinal pigment epithelium by effective MEK inhibition.
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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.