Irene L.M. Reijers , Alexander M. Menzies , Marta Lopez-Yurda , Judith M. Versluis , Elisa A. Rozeman , Robyn P.M. Saw , Winan J. van Houdt , Ellen Kapiteijn , Astrid A.M. van der Veldt , Karijn P.M. Suijkerbuijk , Hanna Eriksson , Geke A.P. Hospers , Willem M.C. Klop , Alejandro Torres Acosta , Lindsay Grijpink-Ongering , Maria Gonzalez , Anja van der Wal , Abrahim Al-Mamgani , Andrew J. Spillane , Richard A. Scolyer , Christian U. Blank
{"title":"个性化反应引导手术和辅助治疗对 III 期黑色素瘤新辅助免疫疗法后生存期的影响:PRADO 和 OpACIN-neo 的 3 年数据比较","authors":"Irene L.M. Reijers , Alexander M. Menzies , Marta Lopez-Yurda , Judith M. Versluis , Elisa A. Rozeman , Robyn P.M. Saw , Winan J. van Houdt , Ellen Kapiteijn , Astrid A.M. van der Veldt , Karijn P.M. Suijkerbuijk , Hanna Eriksson , Geke A.P. Hospers , Willem M.C. Klop , Alejandro Torres Acosta , Lindsay Grijpink-Ongering , Maria Gonzalez , Anja van der Wal , Abrahim Al-Mamgani , Andrew J. Spillane , Richard A. Scolyer , Christian U. Blank","doi":"10.1016/j.ejca.2024.115141","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Pathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies.</div></div><div><h3>Methods</h3><div>The OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma. In OpACIN-neo, all patients underwent therapeutic lymph node dissection (TLND) without subsequent adjuvant therapy. In contrast, PRADO explored a response- directed strategy, where patients achieving a major pathologic response (MPR) omitted TLND and adjuvant therapy, while those without a pathologic response (pNR) received TLND and adjuvant therapy. Here, we provide a descriptive post-hoc comparison of 3-year survival outcomes between the non-personalized approach in OpACIN-neo and the response-directed approach in PRADO.</div></div><div><h3>Results</h3><div>For patients who achieved an MPR, the 3-year recurrence-free survival (RFS) was 93 % for those without TLND versus 96 % for those with TLND (log-rank p = 0.47), and distant metastasis-free survival (DMFS) was 98 % compared to 96 % (log-rank p = 0.49), respectively. For patients with pNR, 3-year RFS rates were 64 % for those receiving adjuvant systemic therapy and 35 % for patients without (log-rank p = 0.10). DMFS rates were 70 % versus 52 % (log-rank p = 0.24), respectively.</div></div><div><h3>Conclusions</h3><div>These data suggest that TLND and adjuvant therapy may be safely omitted in most patients achieving an MPR, while adjuvant systemic therapy following TLND appears to improve RFS and DMFS in patients with pNR. Although these results are hypothesis-generating and require further validation, they offer a potential foundation for developing personalized neoadjuvant immunotherapy approaches.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"214 ","pages":"Article 115141"},"PeriodicalIF":7.6000,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo\",\"authors\":\"Irene L.M. Reijers , Alexander M. Menzies , Marta Lopez-Yurda , Judith M. Versluis , Elisa A. Rozeman , Robyn P.M. Saw , Winan J. van Houdt , Ellen Kapiteijn , Astrid A.M. van der Veldt , Karijn P.M. Suijkerbuijk , Hanna Eriksson , Geke A.P. Hospers , Willem M.C. Klop , Alejandro Torres Acosta , Lindsay Grijpink-Ongering , Maria Gonzalez , Anja van der Wal , Abrahim Al-Mamgani , Andrew J. Spillane , Richard A. Scolyer , Christian U. Blank\",\"doi\":\"10.1016/j.ejca.2024.115141\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Pathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies.</div></div><div><h3>Methods</h3><div>The OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma. In OpACIN-neo, all patients underwent therapeutic lymph node dissection (TLND) without subsequent adjuvant therapy. In contrast, PRADO explored a response- directed strategy, where patients achieving a major pathologic response (MPR) omitted TLND and adjuvant therapy, while those without a pathologic response (pNR) received TLND and adjuvant therapy. Here, we provide a descriptive post-hoc comparison of 3-year survival outcomes between the non-personalized approach in OpACIN-neo and the response-directed approach in PRADO.</div></div><div><h3>Results</h3><div>For patients who achieved an MPR, the 3-year recurrence-free survival (RFS) was 93 % for those without TLND versus 96 % for those with TLND (log-rank p = 0.47), and distant metastasis-free survival (DMFS) was 98 % compared to 96 % (log-rank p = 0.49), respectively. For patients with pNR, 3-year RFS rates were 64 % for those receiving adjuvant systemic therapy and 35 % for patients without (log-rank p = 0.10). DMFS rates were 70 % versus 52 % (log-rank p = 0.24), respectively.</div></div><div><h3>Conclusions</h3><div>These data suggest that TLND and adjuvant therapy may be safely omitted in most patients achieving an MPR, while adjuvant systemic therapy following TLND appears to improve RFS and DMFS in patients with pNR. Although these results are hypothesis-generating and require further validation, they offer a potential foundation for developing personalized neoadjuvant immunotherapy approaches.</div></div>\",\"PeriodicalId\":11980,\"journal\":{\"name\":\"European Journal of Cancer\",\"volume\":\"214 \",\"pages\":\"Article 115141\"},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2024-11-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0959804924017489\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0959804924017489","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo
Background
Pathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies.
Methods
The OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma. In OpACIN-neo, all patients underwent therapeutic lymph node dissection (TLND) without subsequent adjuvant therapy. In contrast, PRADO explored a response- directed strategy, where patients achieving a major pathologic response (MPR) omitted TLND and adjuvant therapy, while those without a pathologic response (pNR) received TLND and adjuvant therapy. Here, we provide a descriptive post-hoc comparison of 3-year survival outcomes between the non-personalized approach in OpACIN-neo and the response-directed approach in PRADO.
Results
For patients who achieved an MPR, the 3-year recurrence-free survival (RFS) was 93 % for those without TLND versus 96 % for those with TLND (log-rank p = 0.47), and distant metastasis-free survival (DMFS) was 98 % compared to 96 % (log-rank p = 0.49), respectively. For patients with pNR, 3-year RFS rates were 64 % for those receiving adjuvant systemic therapy and 35 % for patients without (log-rank p = 0.10). DMFS rates were 70 % versus 52 % (log-rank p = 0.24), respectively.
Conclusions
These data suggest that TLND and adjuvant therapy may be safely omitted in most patients achieving an MPR, while adjuvant systemic therapy following TLND appears to improve RFS and DMFS in patients with pNR. Although these results are hypothesis-generating and require further validation, they offer a potential foundation for developing personalized neoadjuvant immunotherapy approaches.
期刊介绍:
The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.