دورية أكاديمية
Neoadjuvant Dual Checkpoint Inhibitors vs Anti-PD1 Therapy in High-Risk Resectable Melanoma: A Pooled Analysis.
| العنوان: | Neoadjuvant Dual Checkpoint Inhibitors vs Anti-PD1 Therapy in High-Risk Resectable Melanoma: A Pooled Analysis. |
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| المؤلفون: | Mangla A; Department of Hematology and Oncology, University Hospitals Seidman Cancer Center, Cleveland, Ohio.; Department of Hematology and Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio.; Case Comprehensive Cancer Center, Cleveland, Ohio., Lee C; Department of Internal Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio., Mirsky MM; Department of Hematology and Oncology, University Hospitals Seidman Cancer Center, Cleveland, Ohio.; Department of Hematology and Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Wang M; Department of Internal Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio., Rothermel LD; Case Comprehensive Cancer Center, Cleveland, Ohio.; Department of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, Ohio., Hoehn R; Case Comprehensive Cancer Center, Cleveland, Ohio.; Department of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, Ohio., Bordeaux JS; Case Comprehensive Cancer Center, Cleveland, Ohio.; Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, Ohio., Carroll BT; Case Comprehensive Cancer Center, Cleveland, Ohio.; Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, Ohio., Theuner J; Case Comprehensive Cancer Center, Cleveland, Ohio.; Department of Otolaryngology, University Hospitals Cleveland Medical Center, Cleveland Ohio., Li S; Case Comprehensive Cancer Center, Cleveland, Ohio.; Department of Otolaryngology, University Hospitals Cleveland Medical Center, Cleveland Ohio., Fu P; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio., Kirkwood JM; Department of Medicine and Dermatology, UPMC Hillman Cancer Center and Melanoma and Skin Cancer Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. |
| المصدر: | JAMA oncology [JAMA Oncol] 2024 May 01; Vol. 10 (5), pp. 612-620. |
| نوع المنشور: | Journal Article; Comparative Study; Meta-Analysis |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Medical Association Country of Publication: United States NLM ID: 101652861 Publication Model: Print Cited Medium: Internet ISSN: 2374-2445 (Electronic) Linking ISSN: 23742437 NLM ISO Abbreviation: JAMA Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Chicago, Il : American Medical Association, [2015]- |
| مواضيع طبية MeSH: | Immune Checkpoint Inhibitors*/therapeutic use , Immune Checkpoint Inhibitors*/adverse effects , Immune Checkpoint Inhibitors*/administration & dosage , Melanoma*/drug therapy , Melanoma*/immunology , Melanoma*/pathology , Neoadjuvant Therapy*/adverse effects , Nivolumab*/therapeutic use , Nivolumab*/administration & dosage , Nivolumab*/adverse effects , Programmed Cell Death 1 Receptor*/antagonists & inhibitors, Female ; Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Ipilimumab/therapeutic use ; Ipilimumab/administration & dosage ; Ipilimumab/adverse effects |
| مستخلص: | Importance: Despite the clear potential benefits of neoadjuvant therapy, the optimal neoadjuvant regimen for patients with high-risk resectable melanoma (HRRM) is not known. Objective: To compare the safety and efficacy of dual checkpoint inhibitors with anti-programmed cell death protein-1 (anti-PD1) therapy in a neoadjuvant setting among patients with HRRM. Design, Setting, and Participants: In this pooled analysis of clinical trials, studies were selected provided they investigated immune checkpoint inhibitor treatment, were published between January 2018 and March 2023, and were phase 1, 2, or 3 clinical trials. Participant data included in the analysis were derived from trials evaluating the efficacy and safety of anti-PD1 monotherapy and the combination of anti-cytotoxic T lymphocyte-associated protein-4 with anti-PD1 in the neoadjuvant setting, specifically among patients with HRRM. Interventions: Patients were treated with either anti-PD1 monotherapy; dual checkpoint inhibition (DCPI) with a conventional dose of 3-mg/kg ipilimumab and 1-mg/kg nivolumab; or DCPI with an alternative-dose regimen of 1-mg/kg ipilimumab and 3-mg/kg nivolumab. Main Outcomes and Measures: The main outcomes were radiologic complete response (rCR), radiologic overall objective response (rOOR), and radiologic progressive disease. Also, pathologic complete response (pCR), the proportion of patients undergoing surgical resection, and occurrence of grade 3 or 4 immune-related adverse events (irAEs) were considered. Results: Among 573 patients enrolled in 6 clinical trials, neoadjuvant therapy with DCPI was associated with higher odds of achieving pCR compared with anti-PD1 monotherapy (odds ratio [OR], 3.16; P < .001). DCPI was associated with higher odds of grade 3 or 4 irAEs compared with anti-PD1 monotherapy (OR, 3.75; P < .001). When comparing the alternative-dose ipilimumab and nivolumab (IPI-NIVO) regimen with conventional-dose IPI-NIVO, no statistically significant difference in rCR, rOOR, radiologic progressive disease, or pCR was noted. However, the conventional-dose IPI-NIVO regimen was associated with increased grade 3 or 4 irAEs (OR, 4.76; P < .001). Conventional-dose IPI-NIVO was associated with greater odds of achieving improved rOOR (OR, 1.95; P = .046) and pCR (OR, 2.99; P < .001) compared with anti-PD1 monotherapy. The alternative dose of IPI-NIVO also was associated with higher odds of achieving rCR (OR, 2.55; P = .03) and pCR (OR, 3.87; P < .001) compared with anti-PD1 monotherapy. The risk for grade 3 or 4 irAEs is higher with both the conventional-dose (OR, 9.59; P < .001) and alternative-dose IPI-NIVO regimens (OR, 2.02; P = .02) compared with anti-PD1 monotherapy. Conclusion and Relevance: In this pooled analysis of 6 clinical trials, although DCPI was associated with increased likelihood of achieving pathological and radiologic responses, the associated risk for grade 3 or 4 irAEs was significantly lower with anti-PD1 monotherapy in the neoadjuvant setting for HRRM. Additionally, compared with alternative-dose IPI-NIVO, the conventional dose of IPI-NIVO was associated with increased risk for grade 3 or 4 irAEs, with no significant distinctions in radiologic or pathologic efficacy. |
| التعليقات: | Erratum in: JAMA Oncol. 2024 Jul 11. doi: 10.1001/jamaoncol.2024.3182. (PMID: 38990527) |
| المشرفين على المادة: | 0 (PDCD1 protein, human) |
| تواريخ الأحداث: | Date Created: 20240328 Date Completed: 20240516 Latest Revision: 20240711 |
| رمز التحديث: | 20240711 |
| مُعرف محوري في PubMed: | PMC10979364 |
| DOI: | 10.1001/jamaoncol.2023.7333 |
| PMID: | 38546551 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2374-2445 |
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| DOI: | 10.1001/jamaoncol.2023.7333 |