Huang Raymond Y, Youssef Gilbert, Nelson Thomas, Wen Patrick Y, Forsyth Peter, Hodi F Stephen, Margolin Kim, Algazi Alain P, Hamid Omid, Lao Christopher D, Ernstoff Marc S, Moschos Stergios J, Atkins Michael B, Postow Michael A, Reardon David A, Grootendorst Diederik J, Leung David, Askelson Margarita, Ritchings Corey, Tawbi Hussein A
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA.
J Clin Oncol. 2025 Apr;43(10):1210-1218. doi: 10.1200/JCO.24.00953. Epub 2025 Jan 3.
In CheckMate 204, nivolumab + ipilimumab showed high intracranial (IC) objective response rates (icORRs) in patients with melanoma brain metastases (MBMs). Using icORR as a surrogate for overall survival (OS) has prompted use of alternate response criteria. To set the stage for harmonized MBM trials, the aim of this exploratory analysis was to determine icORR using several response criteria and examine correlations of response with survival.
Patients (N = 119) with ≥one unirradiated MBMs received nivolumab + ipilimumab every 3 weeks (four doses), followed by nivolumab every 2 weeks for ≤24 months. Blinded review icORR was assessed with modified RECIST (mRECIST), Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM; 5 mm and 10 mm cutoffs), and volumetric criteria (5 mm and 10 mm). Using a 6-week response landmark, IC progression-free survival (icPFS) and OS were compared for responders versus nonresponders.
icORR was higher with mRECIST and volumetric criteria than with RANO-BM or RECIST. mRECIST and volumetric response also showed stronger correlations with icPFS and OS. mRECIST responders who were RANO-BM 5 mm nonresponders (n = 14) had similar OS to RANO-BM 5 mm responders (n = 41). Clinical deterioration affected RANO-BM icORR; however, when assessed only radiographically without deterioration, RANO-BM 5 mm performed similarly to mRECIST. Among 41 patients with target lesions all <10 mm, responder icPFS and OS were similar to those of responders in the total population, indicating that response could be accurately determined in these patients.
This analysis supports mRECIST or radiographic-only RANO-BM 5 mm as reliable assessment scales in MBM trials. Volumetric response correlated with survival, supporting its application in future trials. Response could be accurately determined in patients with MBMs all <10 mm, supporting the inclusion of patients with MBMs ≥5 mm in future trials.
在CheckMate 204研究中，纳武利尤单抗联合伊匹木单抗在黑色素瘤脑转移（MBM）患者中显示出较高的颅内（IC）客观缓解率（icORR）。将icORR作为总生存期（OS）的替代指标促使人们采用其他缓解标准。为统一MBM试验奠定基础，这项探索性分析的目的是使用多种缓解标准确定icORR，并研究缓解与生存的相关性。
患有≥1处未接受过放疗的MBM的患者（N = 119）每3周接受一次纳武利尤单抗联合伊匹木单抗治疗（共4剂），随后每2周接受纳武利尤单抗治疗≤24个月。采用改良的RECIST（mRECIST）、神经肿瘤脑转移瘤疗效评估（RANO-BM；5 mm和10 mm截断值）以及体积标准（5 mm和10 mm）对盲态审核的icORR进行评估。使用6周缓解界标，比较缓解者与未缓解者的IC无进展生存期（icPFS）和OS。
mRECIST和体积标准的icORR高于RANO-BM或RECIST。mRECIST和体积缓解与icPFS和OS也显示出更强的相关性。mRECIST缓解但RANO-BM 5 mm未缓解的患者（n = 14）的OS与RANO-BM 5 mm缓解的患者（n = 41）相似。临床病情恶化影响RANO-BM的icORR；然而，仅通过影像学评估且无病情恶化时，RANO-BM 5 mm的表现与mRECIST相似。在41例所有靶病灶均<10 mm的患者中，缓解者的icPFS和OS与总体人群中缓解者相似，这表明在这些患者中可以准确确定缓解情况。
该分析支持mRECIST或仅影像学的RANO-BM 5 mm作为MBM试验中可靠的评估量表。体积缓解与生存相关，支持其在未来试验中的应用。对于所有MBM均<10 mm的患者可以准确确定缓解情况，支持在未来试验中纳入MBM≥5 mm的患者。
