Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Now at Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, PA, USA.
Cancer. 2022 Dec 15;128(24):4203-4212. doi: 10.1002/cncr.34493. Epub 2022 Oct 19.
At an interim analysis (median follow-up, 6.2 months; n = 187), the phase 3 COSMIC-311 trial met the primary end point of progression-free survival (PFS): cabozantinib improved PFS versus a placebo (median, not reached vs. 1.9 months; p < .0001) in patients with previously treated radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). The results from an exploratory analysis using an extended datacut are presented.
Patients 16 years old or older with RAIR-DTC who progressed on prior lenvatinib and/or sorafenib were randomized 2:1 to oral cabozantinib tablets (60 mg/day) or a placebo. Placebo patients could cross over to open-label cabozantinib upon radiographic disease progression. The objective response rate (ORR) in the first 100 randomized patients and the PFS in the intent-to-treat population, both according to Response Evaluation Criteria in Solid Tumors version 1.1 by blinded, independent review, were the primary end points.
At the data cutoff (February 8, 2021), 258 patients had been randomized (cabozantinib, n = 170; placebo, n = 88); the median follow-up was 10.1 months. The median PFS was 11.0 months (96% confidence interval [CI], 7.4-13.8 months) for cabozantinib and 1.9 months (96% CI, 1.9-3.7 months) for the placebo (hazard ratio, 0.22; 96% CI, 0.15-0.32; p < .0001). The ORR was 11.0% (95% CI, 6.9%-16.9%) versus 0% (95% CI, 0.0%-4.1%) (p = .0003) with one complete response with cabozantinib. Forty placebo patients crossed over to open-label cabozantinib. Grade 3/4 treatment-emergent adverse events occurred in 62% and 28% of the cabozantinib- and placebo-treated patients, respectively; the most common were hypertension (12% vs. 2%), palmar-plantar erythrodysesthesia (10% vs. 0%), and fatigue (9% vs. 0%). There were no grade 5 treatment-related events.
At extended follow-up, cabozantinib maintained superior efficacy over a placebo in patients with previously treated RAIR-DTC with no new safety signals.
在中期分析（中位随访 6.2 个月；n=187）时，3 期 COSMIC-311 试验达到了无进展生存期（PFS）的主要终点：卡博替尼与安慰剂相比改善了 PFS（中位无进展生存期，未达到 vs. 1.9 个月；p<.0001），用于治疗先前接受过放射性碘难治性分化型甲状腺癌（RAIR-DTC）的患者。现将使用扩展数据截止点的探索性分析结果呈现如下。
16 岁及以上、接受过 lenvatinib 和/或 sorafenib 治疗后疾病进展的 RAIR-DTC 患者，按 2:1 的比例随机分配接受口服卡博替尼片（60mg/天）或安慰剂治疗。在影像学疾病进展时，安慰剂组患者可交叉接受开放标签卡博替尼治疗。根据盲法独立评估的实体瘤反应评价标准 1.1，100 例随机患者的客观缓解率（ORR）和意向治疗人群的 PFS 是主要终点。
截至数据截止日期（2021 年 2 月 8 日），258 例患者被随机分组（卡博替尼组，n=170；安慰剂组，n=88）；中位随访时间为 10.1 个月。卡博替尼组的中位 PFS 为 11.0 个月（96%置信区间[CI]，7.4-13.8 个月），安慰剂组为 1.9 个月（96%CI，1.9-3.7 个月）（风险比，0.22；96%CI，0.15-0.32；p<.0001）。ORR 分别为 11.0%（95%CI，6.9%-16.9%）和 0%（95%CI，0.0%-4.1%）（p=0.0003），卡博替尼组有 1 例完全缓解。40 例安慰剂患者交叉接受开放标签卡博替尼治疗。卡博替尼组和安慰剂组分别有 62%和 28%的患者发生 3/4 级治疗相关不良事件，最常见的是高血压（12% vs. 2%）、手足综合征（10% vs. 0%）和疲劳（9% vs. 0%）。无 5 级治疗相关不良事件。
在延长随访中，卡博替尼在先前接受过治疗的 RAIR-DTC 患者中，与安慰剂相比，疗效保持优势，无新的安全信号。
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