Reckamp Karen L, Lin Huamao M, Cranmer Holly, Wu Yanyu, Zhang Pingkuan, Kay Stephen, Walton Laura J, Shen Junwu, Popat Sanjay, Camidge D Ross
Division of Medical Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Global Evidence and Outcome, Takeda Development Center Americas Inc., Lexington, MA, USA.
Curr Med Res Opin. 2022 Sep;38(9):1587-1593. doi: 10.1080/03007995.2022.2100653. Epub 2022 Jul 29.
Second-generation anaplastic lymphoma kinase ( gene targeted tyrosine kinase inhibitors (TKIs) alectinib and brigatinib have shown efficacy as front-line treatments for -positive non-small cell lung cancer (NSCLC). No head-to-head data are currently available for brigatinib vs alectinib in the ALK-TKI-naive population.
To estimate the relative overall survival (OS) for brigatinib vs alectinib with indirect treatment comparisons (ITCs) using ALEX and ALTA-1L clinical trial data.
The latest aggregate data from the ALEX trial and final patient-level data from ALTA-1L were used. ITCs were conducted with/without treatment crossover adjustments to estimate relative OS. Bucher methods, anchored matching-adjusted indirect comparisons (MAICs) and unanchored MAICs were employed in ITCs without treatment crossover adjustments. An inverse probability of censoring weight Cox model, a marginal structure model and rank-preserving structural failure time models (with/without re-censoring) within an anchored MAIC were used in ITCs with treatment crossover adjustments. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported.
HRs for brigatinib vs alectinib for relative OS generated from ITCs without treatment crossover adjustments ranged from 0.90 (95% CI: 0.59-1.38) in the unanchored MAIC to 1.20 (95% CI: 0.69-2.11) using the Bucher method. Methods employing treatment switching adjustments estimated HRs for relative OS ranging from 0.74 (95% CI: 0.38-1.45) to 1.11 (95% CI: 0.63-1.94). Results from all ITCs did not indicate statistically different survival profiles.
Regardless of ITC methodology, OS is comparable for brigatinib vs alectinib in patients with + NSCLC previously untreated with an ALK inhibitor.
第二代间变性淋巴瘤激酶（ALK）基因靶向酪氨酸激酶抑制剂（TKIs）阿来替尼和布加替尼已显示出作为ALK阳性非小细胞肺癌（NSCLC）一线治疗的疗效。目前尚无布加替尼与阿来替尼在初治ALK-TKI人群中的直接对比数据。
使用ALEX和ALTA-1L临床试验数据，通过间接治疗比较（ITC）估计布加替尼与阿来替尼的相对总生存期（OS）。
使用ALEX试验的最新汇总数据和ALTA-1L的最终患者层面数据。在有/无治疗交叉调整的情况下进行ITC以估计相对OS。在无治疗交叉调整的ITC中采用布彻方法、锚定匹配调整间接比较（MAIC）和非锚定MAIC。在有治疗交叉调整的ITC中，在锚定MAIC内使用删失权重逆概率Cox模型、边际结构模型和秩保持结构失效时间模型（有/无重新删失）。报告风险比（HRs）和95%置信区间（CIs）。
在无治疗交叉调整的ITC中，布加替尼与阿来替尼相对OS的HRs范围从非锚定MAIC中的0.90（95%CI：0.59-1.38）到使用布彻方法的1.20（95%CI：0.69-2.11）。采用治疗转换调整的方法估计相对OS的HRs范围为0.74（95%CI：0.38-1.45）至1.11（95%CI：0.63-1.94）。所有ITC的结果均未表明生存情况有统计学差异。
无论ITC方法如何，在先前未接受过ALK抑制剂治疗的ALK阳性NSCLC患者中，布加替尼与阿来替尼的OS相当。
