荷兰癌症研究所Christian U. Blank团队完成高危III期黑色素瘤新辅助治疗ipilimumab和nivolumab后个性化反应导向的手术和辅助治疗的临床试验。这一研究成果于2022年6月5日在线发表在国际学术期刊《自然—医学》上。

Author: Reijers, Irene L. M., Menzies, Alexander M., van Akkooi, Alexander C. J., Versluis, Judith M., van den Heuvel, Nolle M. J., Saw, Robyn P. M., Pennington, Thomas E., Kapiteijn, Ellen, van der Veldt, Astrid A. M., Suijkerbuijk, Karijn P. M., Hospers, Geke A. P., Rozeman, Elisa A., Klop, Willem M. C., van Houdt, Winan J., Sikorska, Karolina, van der Hage, Jos A., Grnhagen, Dirk J., Wouters, Michel W., Witkamp, Arjen J., Zuur, Charlotte L., Lijnsvelt, Judith M., Torres Acosta, Alejandro, Grijpink-Ongering, Lindsay G., Gonzalez, Maria, Jwiak, Katarzyna, Bierman, Carolien, Shannon, Kerwin F., Chng, Sydney, Colebatch, Andrew J., Spillane, Andrew J., Haanen, John B. A. G., Rawson, Robert V., van de Wiel, Bart A., van de Poll-Franse, Lonneke V., Scolyer, Richard A., Boekhout, Annelies H., Long, Georgina V., Blank, Christian U.

Issue&Volume: 2022-06-05

Abstract: 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 6weeks of neoadjuvant ipilimumab 1mgkg1 and nivolumab 3mgkg1. 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 24months 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 12weeks 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.

DOI: 10.1038/s41591-022-01851-x

Source: https://www.nature.com/articles/s41591-022-01851-x