Diem S, Kasenda B, Spain L, Martin-Liberal J, Marconcini R, Gore M, Larkin J
Department of Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London SW36JJ, UK.
Department of Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, 119-129, 08035 Barcelona, Spain.
Br J Cancer. 2016 Feb 2;114(3):256-61. doi: 10.1038/bjc.2015.467. Epub 2016 Jan 21.
Treatment with programmed death receptor-1 (PD-1) antibodies is associated with high response rates in patients with advanced melanoma. Reliable markers for early response and outcome are still sparse.
We evaluated 66 consecutive patients with advanced/metastatic melanoma treated with nivolumab or pembrolizumab between 2013 and 2014. The main objectives of this study were to investigate whether, first, serum lactate dehydrogenase (LDH) at baseline (normal vs above the upper limit of normal) correlates with overall survival (OS), and, second, whether the change of LDH during treatment predicts response before the first scan and OS in patients with an elevated baseline LDH.
After a median follow-up of 9 months, patients with an elevated baseline LDH (N=34) had a significantly shorter OS compared with patients with normal LDH (N=32; 6-month OS: 60.8% vs 81.6% and 12-month OS: 44.2% vs 71.5% (log-rank P=0.0292). In those 34 patients with elevated baseline LDH, the relative change during treatment was significantly associated with an objective response on the first scan: the 11 (32%) patients with partial remission had a mean reduction of -27.3% from elevated baseline LDH. In contrast, patients with progressive disease (N=15) had a mean increase of +39%. Patients with a relative increase over 10% from elevated baseline LDH had a significantly shorter OS compared with patients with ⩽ 10% change (4.3 vs 15.7 months, log-rank P<0.00623).
LDH could be a useful marker at baseline and during treatment to predict early response or progression in patients with advanced melanoma who receive anti-PD-1 therapy.
程序性死亡受体-1(PD-1)抗体治疗晚期黑色素瘤患者的缓解率较高。早期反应和预后的可靠标志物仍然很少。
我们评估了2013年至2014年间连续接受纳武单抗或帕博利珠单抗治疗的66例晚期/转移性黑色素瘤患者。本研究的主要目的是,首先,调查基线时血清乳酸脱氢酶(LDH)(正常与高于正常上限)是否与总生存期(OS)相关;其次,对于基线LDH升高的患者,治疗期间LDH的变化是否能在首次扫描前预测反应和OS。
中位随访9个月后,基线LDH升高的患者(N = 34)的OS明显短于LDH正常的患者(N = 32;6个月OS:60.8%对81.6%,12个月OS:44.2%对71.5%(对数秩检验P = 0.0292)。在这34例基线LDH升高的患者中,治疗期间的相对变化与首次扫描时的客观反应显著相关:11例(32%)部分缓解的患者基线LDH升高后平均降低了-27.3%。相比之下,疾病进展的患者(N = 15)平均升高了+39%。与变化≤10%的患者相比,基线LDH升高后相对升高超过10%的患者OS明显更短(4.3个月对15.7个月,对数秩检验P<0.00623)。
LDH可能是晚期黑色素瘤患者接受抗PD-1治疗时预测早期反应或进展的有用基线和治疗期间标志物。