Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Solna, Sweden.
ICON Plc, ICO, Stockholm, Sweden.
PLoS One. 2020 May 12;15(5):e0232669. doi: 10.1371/journal.pone.0232669. eCollection 2020.
We assessed the impact of new antineoplastic agents on the overall survival (OS) of advanced non-small cell lung cancer (aNSCLC) patients followed up until 2012. Multivariate regression models were run for OS (outcome) and four proxies for innovation (exposure): Index (InnovInd, for SEER-Research data 1973-2012) and three levels of aggregation of Mean Medication Vintage, i.e. Overall (MMVOverall), using data aggregated at the State Level (MMVState), and using patient-level data (MMVPatient) using data from the US captured in SEER-Medicare 1991-2012. We derived Hazard ratios (HR) from Royston-Parmar models and odds ratios (OR) from a logistic regression on 1-year OS. Including 164,704 patients (median age 72 years, 56.8% stage IV, 61.8% with no comorbidities, 37.8% with adenocarcinoma, 22.9% with squamous-cell, 6.1% were censored). One-year OS improved from 0.22 in 1973 to 0.39 in 2012, in correlation with InnovInd (r = 0.97). Ten new NSCLC drugs were approved and 28 more used off-label. Regression-models results indicate that therapeutic innovation only marginally reduced the risk of dying (HROverall = 0.98 [0.98-0.98], HRMMV-Patient = 0.98 [0.97-0.98], and HRMMV-State = 0.98 [0.98-0.98], and slightly improved 1-year survival (ORMMV-Overall = 1.05 95%CI [1.04-1.05]). These results were validated with data from the Swedish National Health Data registers. Until 2013, aNSCLC patients were treated undifferentiated and the introduction of innovative therapies had statistically significant, albeit modest, effects on survival. Most treatments used off-guidelines highlight the high unmet need; however new advancements in treatment may further improve survival.
我们评估了新的抗肿瘤药物对晚期非小细胞肺癌（aNSCLC）患者总体生存（OS）的影响，这些患者的随访时间截至 2012 年。我们对 OS（结局）和四个创新指标（暴露）进行了多变量回归模型分析：指数（InnovInd，用于 SEER-Research 数据 1973-2012）和三种平均药物使用年限的聚合水平，即总体（MMVOverall），使用州级数据（MMVState）和使用患者级数据（MMVPatient），数据来源于 1991-2012 年 SEER- Medicare 捕获的数据。我们使用 Royston-Parmar 模型得出风险比（HR），使用逻辑回归得出 1 年 OS 的比值比（OR）。纳入 164704 名患者（中位年龄 72 岁，56.8%为 IV 期，61.8%无合并症，37.8%为腺癌，22.9%为鳞状细胞癌，6.1%被删失）。1973 年 1 年 OS 为 0.22，2012 年为 0.39，与 InnovInd 呈正相关（r=0.97）。批准了 10 种新的 NSCLC 药物，28 种药物超适应证使用。回归模型结果表明，治疗创新仅略微降低了死亡风险（HROverall=0.98[0.98-0.98]，HRMMV-Patient=0.98[0.97-0.98]，HRMMV-State=0.98[0.98-0.98]），略微提高了 1 年生存率（ORMMV-Overall=1.0595%CI[1.04-1.05]）。这些结果通过瑞典国家健康数据登记处的数据得到验证。直到 2013 年，aNSCLC 患者的治疗方法都没有区别，创新疗法的引入对生存有统计学意义，但影响较小。大多数超适应证使用的治疗方法突出了高度未满足的需求；然而，新的治疗进展可能会进一步提高生存率。
