皮肤毒性作为西妥昔单抗联合阿维鲁单抗治疗（CAVE再激发策略）的野生型转移性结直肠癌难治性患者生存预测指标
Skin Toxicity as Predictor of Survival in Refractory Patients with Wild-Type Metastatic Colorectal Cancer Treated with Cetuximab and Avelumab (CAVE) as Rechallenge Strategy.
作者信息
Ciardiello Davide, Famiglietti Vincenzo, Napolitano Stefania, Esposito Lucia, Normanno Nicola, Avallone Antonio, Latiano Tiziana, Maiello Evaristo, Pietrantonio Filippo, Cremolini Chiara, Santabarbara Giuseppe, Pinto Carmine, Troiani Teresa, Martinelli Erika, Ciardiello Fortunato, Martini Giulia
机构信息
Oncologia Medica, Dipartimento di Medicina di Precisione, Università degli Studi della Campania "L. Vanvitelli", 80131 Napoli, Italy.
Oncologia Medica, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.
出版信息
Cancers (Basel). 2021 Nov 15;13(22):5715. doi: 10.3390/cancers13225715.
The single-arm phase II CAVE mCRC trial evaluated the combination of cetuximab plus avelumab as rechallenge strategy in wild-type (WT) metastatic colorectal cancer (mCRC) patients, with clinical response to first-line anti-EGFR-based chemotherapy, who progressed and received a subsequent line of therapy. The correlation of skin toxicity (ST) and different clinico-molecular variables with overall survival (OS), progression-free survival (PFS) and response rate (RR) was assessed at univariate and multivariate analysis. A total of 33/77 (42.9%) patients experienced grade 2-3 ST and displayed median OS (mOS) of 17.8 months (CI 95%, 14.9-20.6); whereas 44/77 (57.1%) patients with grade 0-1 ST exhibited mOS of 8.2 months (CI 95%, 5.5-10.9), (hazard ratio (HR), 0.51; CI 95%, 0.29-0.89; = 0.019). Median PFS (mPFS) was 4.6 months (CI 95%, 3.4-5.7) in patients with grade 2-3 ST, compared to patients with grade 0-1 ST with mPFS of 3.4 months (CI 95%, 2.7-4.1; HR, 0.49; CI 95%, 0.3-0.8; = 0.004). Grade 2-3 ST (HR, 0.51; CI 95%, 0.29-0.89; = 0.019) and WT circulating tumor DNA (ctDNA) (HR, 0.50; CI 95%, 0.27-0.9; = 0.019) had a statistically significant effect on OS at univariate analysis. At the multivariate analysis, WT ctDNA status maintained statistical significance (HR, 0.49; CI 95%, 0.27-0.9; = 0.023), whereas there was a trend towards ST grade 2-3 (HR, 0.54; CI 95%, 0.29-1.01; = 0.054). Skin toxicity is a promising biomarker to identify patients with mCRC that could benefit of anti-EGFR rechallenge.
单臂II期CAVE mCRC试验评估了西妥昔单抗联合阿维鲁单抗作为再挑战策略，用于一线抗表皮生长因子受体（EGFR）化疗有临床反应、病情进展并接受后续治疗的野生型（WT）转移性结直肠癌（mCRC）患者。在单变量和多变量分析中评估了皮肤毒性（ST）以及不同临床分子变量与总生存期（OS）、无进展生存期（PFS）和缓解率（RR）之间的相关性。共有33/77（42.9%）例患者发生2-3级ST，其总生存期（mOS）中位数为17.8个月（95%置信区间，14.9-20.6）；而44/77（57.1%）例0-1级ST患者的mOS为8.2个月（95%置信区间，5.5-10.9），（风险比（HR）为0.51；95%置信区间，0.29-0.89；P=0.019）。2-3级ST患者的无进展生存期（mPFS）中位数为4.6个月（95%置信区间，3.4-5.7），而0-1级ST患者的mPFS为3.4个月（95%置信区间，2.7-4.1；HR为0.49；95%置信区间，0.3-0.8；P=0.004）。单变量分析中，2-3级ST（HR为0.51；95%置信区间，0.29-0.89；P=0.019）和WT循环肿瘤DNA（ctDNA）（HR为0.50；95%置信区间，0.27-0.9；P=0.019）对OS有统计学显著影响。多变量分析中，WT ctDNA状态保持统计学显著性（HR为0.49；95%置信区间，0.27-0.9；P=0.023），而2-3级ST有一定趋势（HR为0.54；95%置信区间，0.29-1.01；P=0.054）。皮肤毒性是一种有前景的生物标志物，可用于识别可能从抗EGFR再挑战中获益的mCRC患者。
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