Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma
| العنوان: | Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma |
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| المؤلفون: | Irene L. M. Reijers, Alexander M. Menzies, Alexander C. J. van Akkooi, Judith M. Versluis, Noëlle M. J. van den Heuvel, Robyn P. M. Saw, Thomas E. Pennington, Ellen Kapiteijn, Astrid A. M. van der Veldt, Karijn P. M. Suijkerbuijk, Geke A. P. Hospers, Elisa A. Rozeman, Willem M. C. Klop, Winan J. van Houdt, Karolina Sikorska, Jos A. van der Hage, Dirk J. Grünhagen, Michel W. Wouters, Arjen J. Witkamp, Charlotte L. Zuur, Judith M. Lijnsvelt, Alejandro Torres Acosta, Lindsay G. Grijpink-Ongering, Maria Gonzalez, Katarzyna Jóźwiak, Carolien Bierman, Kerwin F. Shannon, Sydney Ch’ng, Andrew J. Colebatch, Andrew J. Spillane, John B. A. G. Haanen, Robert V. Rawson, Bart A. van de Wiel, Lonneke V. van de Poll-Franse, Richard A. Scolyer, Annelies H. Boekhout, Georgina V. Long, Christian U. Blank |
| المساهمون: | Medical and Clinical Psychology, Oral and Maxillofacial Surgery, Medical Oncology, Radiology & Nuclear Medicine, Surgery, Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| المصدر: | Nature Medicine, 28(6), 1178-+. NATURE PORTFOLIO Nature Medicine, 28(6), 1178-1188. Nature Publishing Group Nature Medicine Nature medicine, 28(6), 1178-1188. Nature Publishing Group Nature Medicine, 28. Nature Publishing Group |
| بيانات النشر: | Nature Publishing Group, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Skin Neoplasms, General Medicine, BIOMARKER ANALYSES, Ipilimumab, Neoadjuvant Therapy, General Biochemistry, Genetics and Molecular Biology, MORBIDITY, Nivolumab, QUALITY-OF-LIFE, Antineoplastic Combined Chemotherapy Protocols, Quality of Life, BIOPSY, SURVIVAL, Humans, AXILLARY, Neoplasm Recurrence, Local, IMMUNOTHERAPY, Melanoma, DISSECTION, SENTINEL LYMPH-NODE, Neoplasm Staging |
| الوصف: | Neoadjuvant ipilimumab and nivolumab induces high pathologic response rates (pRRs) in clinical stage III nodal melanoma, and pathologic response is strongly associated with prolonged relapse-free survival (RFS). The PRADO extension cohort of the OpACIN-neo trial ( NCT02977052 ) addressed the feasibility and effect on clinical outcome of using pathologic response after neoadjuvant ipilimumab and nivolumab as a criterion for further treatment personalization. In total, 99 patients with clinical stage IIIb-d nodal melanoma were included and treated with 6 weeks of neoadjuvant ipilimumab 1 mg kg-1 and nivolumab 3 mg kg-1. In patients achieving major pathologic response (MPR, ≤10% viable tumor) in their index lymph node (ILN, the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with pathologic partial response (pPR; >10 to ≤50% viable tumor) underwent TLND only, whereas patients with pathologic non-response (pNR; >50% viable tumor) underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy. Primary objectives were confirmation of pRR (ILN, at week 6) of the winner neoadjuvant combination scheme identified in OpACIN-neo; to investigate whether TLND can be safely omitted in patients achieving MPR; and to investigate whether RFS at 24 months can be improved for patients achieving pNR. ILN resection and ILN-response-tailored treatment were feasible. The pRR was 72%, including 61% MPR. Grade 3-4 toxicity within the first 12 weeks was observed in 22 (22%) patients. TLND was omitted in 59 of 60 patients with MPR, resulting in significantly lower surgical morbidity and better quality of life. The 24-month relapse-free survival and distant metastasis-free survival rates were 93% and 98% in patients with MPR, 64% and 64% in patients with pPR, and 71% and 76% in patients with pNR, respectively. These findings provide a strong rationale for randomized clinical trials testing response-directed treatment personalization after neoadjuvant ipilimumab and nivolumab. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1546-170X 1078-8956 0297-7052 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::67d79d3cfe1f3c168f561afa30efdc6cTest https://doi.org/10.1038/s41591-022-01851-xTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....67d79d3cfe1f3c168f561afa30efdc6c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1546170X 10788956 02977052 |
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