Department of Oncology, McGill University Health Centre, Cedars Cancer Centre, Montreal, QC, Canada.
Pharmerit North America, Bethesda, MD.
Clin Lung Cancer. 2018 Sep;19(5):401-409.e4. doi: 10.1016/j.cllc.2018.04.023. Epub 2018 May 7.
First-line nab-paclitaxel/carboplatin was associated with a significantly improved overall response rate (primary endpoint) versus paclitaxel/carboplatin in a phase III trial of advanced non-small-cell lung cancer (NSCLC). We report the results of an analysis evaluating the correlation of response and the time to response with survival and quality-adjusted outcomes.
Using a landmark approach, progression-free survival (PFS), overall survival (OS), and quality-adjusted time without symptoms or toxicity (Q-TWiST) were compared between patients with a confirmed partial or complete response at or before 6 weeks (≤ 6-week responders) and those without (≤ 6-week nonresponders). The outcomes were also analyzed in two 12-week landmark analyses: ≤ 12-week responders versus ≤ 12-week nonresponders and early responders (≤ 6 weeks) versus late responders (6-12 weeks) versus ≤ 12-week nonresponders.
The median OS and PFS for the ≤ 6-week responders versus ≤ 6-week nonresponders were 14.5 versus 10.3 months (P < .001) and 5.5 versus 4.5 months (P = .002), respectively. The ≤ 6-week responders gained 2.1 months of mean Q-TWiST. The median OS and PFS for the ≤ 12-week responders versus ≤ 12-week nonresponders were 16.3 versus 8.4 months and 5.3 versus 2.8 months (both P < .001), respectively, and the ≤ 12-week responders gained 3.2 months of mean Q-TWiST. The median OS was 13.1, 16.6, and 8.4 months (P < .001), the median PFS was 4.1, 6.7, and 2.8 months (P < .001), and the mean Q-TWiST was 10.2, 11.7, and 7.8 months for the early responders, late responders, and ≤ 12-week nonresponders, respectively. Both early and late responders had significantly longer Q-TWiST compared with the ≤ 12-week nonresponders (difference, +2.4 and +3.9 months, respectively; P < .05).
These results underscore response as an important surrogate for assessment of long-term treatment outcomes in advanced NSCLC.
在一项 III 期临床试验中，与紫杉醇/卡铂相比，一线纳布紫杉醇/卡铂显著提高了晚期非小细胞肺癌（NSCLC）患者的总缓解率（主要终点）。我们报告了一项分析结果，该分析评估了缓解和缓解时间与生存和质量调整结局之间的相关性。
使用里程碑方法，比较有确认的部分或完全缓解（6 周或之前）的患者（≤6 周应答者）和无缓解的患者（≤6 周无应答者）之间的无进展生存期（PFS）、总生存期（OS）和无症状或毒性的质量调整时间（Q-TWiST）。还对两个 12 周里程碑分析中的结果进行了分析：≤12 周应答者与≤12 周无应答者和早期应答者（≤6 周）与晚期应答者（6-12 周）与≤12 周无应答者。
≤6 周应答者与≤6 周无应答者的中位 OS 和 PFS 分别为 14.5 个月和 10.3 个月（P<0.001）和 5.5 个月和 4.5 个月（P=0.002）。≤6 周应答者获得了 2.1 个月的平均 Q-TWiST。≤12 周应答者与≤12 周无应答者的中位 OS 和 PFS 分别为 16.3 个月和 8.4 个月和 5.3 个月和 2.8 个月（均 P<0.001），≤12 周应答者获得了 3.2 个月的平均 Q-TWiST。中位 OS 为 13.1、16.6 和 8.4 个月（P<0.001），中位 PFS 为 4.1、6.7 和 2.8 个月（P<0.001），早期应答者、晚期应答者和≤12 周无应答者的平均 Q-TWiST 分别为 10.2、11.7 和 7.8 个月。与≤12 周无应答者相比，早期和晚期应答者的 Q-TWiST 均显著延长（差异分别为+2.4 个月和+3.9 个月；P<0.05）。
这些结果强调了缓解作为评估晚期 NSCLC 长期治疗结局的重要替代指标。
