Ipilimumab alone or in combination with nivolumab in patients with advanced melanoma who have progressed or relapsed on PD-1 blockade: clinical outcomes and translational biomarker analyses
| العنوان: | Ipilimumab alone or in combination with nivolumab in patients with advanced melanoma who have progressed or relapsed on PD-1 blockade: clinical outcomes and translational biomarker analyses |
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| المؤلفون: | Friedman, Claire F, Spencer, Christine, Cabanski, Christopher R, Panageas, Katherine S, Wells, Daniel K, Ribas, Antoni, Tawbi, Hussein, Tsai, Katy, Postow, Michael, Shoushtari, Alexander, Chapman, Paul, Karakunnel, Joyson, Bucktrout, Samantha, Gherardini, Pier, Hollmann, Travis J, Chen, Richard O, Callahan, Margaret, LaVallee, Theresa, Ibrahim, Ramy, Wolchok, Jedd |
| المصدر: | Journal for ImmunoTherapy of Cancer, Vol 10, Iss 1 (2022) Journal for Immunotherapy of Cancer Journal for ImmunoTherapy of Cancer, vol 10, iss 1 |
| بيانات النشر: | BMJ, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Adult, Male, Cancer Research, Immunology, Interferon-gamma, melanoma, Biomarkers, Tumor, Tumor Microenvironment, tumor microenvironment, Humans, Immunology and Allergy, Prospective Studies, Immune Checkpoint Inhibitors, RC254-282, Aged, Clinical/Translational Cancer Immunotherapy, Aged, 80 and over, Pharmacology, Antigen Presentation, Settore BIO/11, Sequence Analysis, RNA, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, Ipilimumab, Nivolumab, Oncology, Molecular Medicine, Female, immunotherapy, Neoplasm Recurrence, Local |
| الوصف: | BackgroundThere are no validated biomarkers that can aid clinicians in selecting who would best benefit from anticytotoxic T lymphocyte-associated antigen 4 monotherapy versus combination checkpoint blockade in patients with advanced melanoma who have progressive disease after programmed death 1 (PD-1) blockade.MethodsWe conducted a randomized multicenter phase II trial in patients with advanced melanoma. Patients were randomly assigned to receive either 1 mg/kg of nivolumab plus 3 mg/kg of ipilimumab or 3 mg/kg of ipilimumab every 3 weeks for up to four doses. Patients were stratified by histological subtype and prior response to PD-1 therapy. The primary clinical objective was overall response rate by week 18. Translational biomarker analyses were conducted in patients with blood and tissue samples.ResultsObjective responses were seen in 5 of 9 patients in the ipilimumab arm and 2 of 10 patients in the ipilimumab+nivolumab arm; disease control rates (DCRs) (66.7% vs 60.0%) and rates of grade 3–4 adverse events (56% vs 50%) were comparable between arms. In a pooled analysis, patients with clinical benefit (CB), defined as Response Evaluation Criteria in Solid Tumors response or progression-free for 6 months, showed increased circulating CD4+ T cells with higher polyfunctionality and interferon gamma production following treatment. Tumor profiling revealed enrichment of NRAS mutations and activation of transcriptional programs associated with innate and adaptive immunity in patients with CB.ConclusionsIn patients with advanced melanoma that previously progressed on PD-1 blockade, objective responses were seen in both arms, with comparable DCRs. Findings from biomarker analyses provided hypothesis-generating signals for validation in future studies of larger patient cohorts.Trial registration numberNCT02731729. |
| وصف الملف: | application/pdf |
| تدمد: | 2051-1426 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ffeb093a9c871f5d5c7ba414f52cdb19Test https://doi.org/10.1136/jitc-2021-003853Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ffeb093a9c871f5d5c7ba414f52cdb19 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20511426 |
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