Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena.
Medical Oncology and Innovative Therapies, Fondazione 'G. Pascale', National Cancer Institute, Naples.
Ann Oncol. 2015 Apr;26(4):798-803. doi: 10.1093/annonc/mdu577. Epub 2014 Dec 23.
In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination.
This analysis captured the 3-year outcome of MM patients who received ipilimumab combined with fotemustine as first- or second-line treatment. Median overall survival (OS), 3-year survival rates, immune-related (ir) progression-free survival (irPFS), brain PFS, and ir duration of response (irDOR) for the entire population and for patients with brain metastases were assessed. Clinical results were correlated with circulating CD3(+)CD4(+)ICOS(+)CD45RO(+) or CD45RA(+) T cells, neutrophil/lymphocyte (N/L) ratios, and tumorBRAF-V600 mutational status.
Eighty-six MM patients, including 20 with asymptomatic brain metastases that had been pre-treated with radiotherapy in 7 subjects, were enrolled in the study. With a median follow-up of 39.9 months, median OS and 3-year survival rates were 12.9 months [95% confidence interval (CI) 7.1-18.7 months] and 28.5% for the whole study population, and 12.7 months (95% CI 2.7-22.7 months) and 27.8% for patients with brain metastases, respectively. Long-term ir adverse events consisting of G1 rush and pruritus occurred in 21% of patients. The absolute increase from baseline to week 12 in 'memory' but not in 'naïve' T cells identified patients with a better survival (P = 0.002). The N/L ratio correlated with a significantly better survival at early time points. BRAF status did not correlate with clinical outcome.
Long-term analysis of the NIBIT-M1 trial continues to demonstrate efficacy of ipilimumab combined with fotemustine in MM patients. Fotemustine does not seem to impair the immunologic activity of ipilimumab.
2010-019356-50.
NCT01654692.
在 NIBIT-M1 研究中，我们报告了伊匹单抗联合福莫司汀在伴或不伴脑转移的转移性黑色素瘤（MM）患者中的有前景的活性。为了证实这些初步发现，我们现在研究了该联合治疗的长期疗效。
本分析捕获了接受伊匹单抗联合福莫司汀作为一线或二线治疗的 MM 患者的 3 年结果。评估了整个人群和有脑转移的患者的中位总生存期（OS）、3 年生存率、免疫相关（ir）无进展生存期（irPFS）、脑 PFS 和 ir 缓解持续时间（irDOR）。临床结果与循环 CD3(+)CD4(+)ICOS(+)CD45RO(+)或 CD45RA(+)T 细胞、中性粒细胞/淋巴细胞（N/L）比值和肿瘤 BRAF-V600 突变状态相关。
86 名 MM 患者，包括 20 名无症状脑转移患者，其中 7 名患者在研究前接受了放疗，该研究纳入了该人群。中位随访 39.9 个月后，整个研究人群的中位 OS 和 3 年生存率分别为 12.9 个月（95%CI 7.1-18.7 个月）和 28.5%，脑转移患者分别为 12.7 个月（95%CI 2.7-22.7 个月）和 27.8%。长期的 ir 不良事件包括 G1 性皮疹和瘙痒，发生在 21%的患者中。与基线相比，在第 12 周时 '记忆'T 细胞而非 '幼稚'T 细胞的绝对增加可识别出具有更好生存的患者（P=0.002）。N/L 比值与早期时间点的生存显著相关。BRAF 状态与临床结果无关。
NIBIT-M1 试验的长期分析继续证明了伊匹单抗联合福莫司汀在 MM 患者中的疗效。福莫司汀似乎不会损害伊匹单抗的免疫活性。
2010-019356-50。
临床试验.gov 编号：NCT01654692。
