Reijers Irene L M, Menzies Alexander M, Lopez-Yurda Marta, Versluis Judith M, Rozeman Elisa A, Saw Robyn P M, van Houdt Winan J, Kapiteijn Ellen, van der Veldt Astrid A M, Suijkerbuijk Karijn P M, Eriksson Hanna, Hospers Geke A P, Klop Willem M C, Torres Acosta Alejandro, Grijpink-Ongering Lindsay, Gonzalez Maria, van der Wal Anja, Al-Mamgani Abrahim, Spillane Andrew J, Scolyer Richard A, van de Wiel Bart A, van Akkooi Alexander C J, Long Georgina V, Blank Christian U
Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Melanoma Institute of Australia, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia.
Eur J Cancer. 2025 Jan;214:115141. doi: 10.1016/j.ejca.2024.115141. Epub 2024 Nov 19.
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.
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.
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.
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.
III期黑色素瘤新辅助免疫检查点阻断（ICB）后的病理反应可作为长期预后的替代标志物。这可能支持更个性化的、基于反应的治疗策略。
OpACIN-neo和PRADO试验是评估伊匹木单抗和纳武利尤单抗用于III期黑色素瘤新辅助治疗的2期研究。在OpACIN-neo试验中，所有患者均接受治疗性淋巴结清扫（TLND），随后未接受辅助治疗。相比之下，PRADO探索了一种基于反应的策略，即达到主要病理反应（MPR）的患者省略TLND和辅助治疗，而无病理反应（pNR）的患者接受TLND和辅助治疗。在此，我们对OpACIN-neo试验中的非个性化方法与PRADO试验中的基于反应的方法之间的3年生存结果进行了描述性事后比较。
对于达到MPR的患者，未进行TLND的患者3年无复发生存率（RFS）为93%，进行TLND的患者为96%（对数秩检验p = 0.47），远处无转移生存率（DMFS）分别为98%和96%（对数秩检验p = 0.49）。对于pNR患者，接受辅助全身治疗的患者3年RFS率为64%，未接受辅助全身治疗的患者为35%（对数秩检验p = 0.10）。DMFS率分别为70%和52%（对数秩检验p = 0.24）。
这些数据表明，大多数达到MPR的患者可安全省略TLND和辅助治疗，而TLND后的辅助全身治疗似乎可改善pNR患者的RFS和DMFS。尽管这些结果只是初步的，需要进一步验证，但它们为开发个性化新辅助免疫治疗方法提供了潜在基础。
