度伐利尤单抗联合铂类-依托泊苷与铂类-依托泊苷一线治疗广泛期小细胞肺癌的患者报告结局（CASPIAN）：一项随机、对照、开放标签的III期研究。
Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study.
作者信息
Goldman Jonathan W, Garassino Marina Chiara, Chen Yuanbin, Özgüroğlu Mustafa, Dvorkin Mikhail, Trukhin Dmytro, Statsenko Galina, Hotta Katsuyuki, Ji Jun Ho, Hochmair Maximilian J, Voitko Oleksandr, Havel Libor, Poltoratskiy Artem, Losonczy György, Reinmuth Niels, Patel Nikunj, Laud Peter J, Shire Norah, Jiang Haiyi, Paz-Ares Luis
机构信息
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
出版信息
Lung Cancer. 2020 Nov;149:46-52. doi: 10.1016/j.lungcan.2020.09.003. Epub 2020 Sep 10.
OBJECTIVES
In the phase III CASPIAN study, first-line durvalumab plus etoposide in combination with either cisplatin or carboplatin (EP) significantly improved overall survival (primary endpoint) versus EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) at the interim analysis. Here we report patient-reported outcomes (PROs).
MATERIALS AND METHODS
Treatment-naïve patients with ES-SCLC received 4 cycles of durvalumab plus EP every 3 weeks followed by maintenance durvalumab every 4 weeks until progression, or up to 6 cycles of EP every 3 weeks. PROs, assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) version 3 and its lung cancer module, the Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), were prespecified secondary endpoints. Changes from baseline to disease progression or 12 months in prespecified key disease-related symptoms (cough, dyspnea, chest pain, fatigue, appetite loss) were analyzed with a mixed model for repeated measures. Time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization was analyzed.
RESULTS
In the durvalumab plus EP and EP arms, 261 and 260 patients were PRO-evaluable. Patients in both arms experienced numerically reduced symptom burden over 12 months or until progression for key symptoms. For the improvements from baseline in appetite loss, the between-arm difference was statistically significant, favoring durvalumab plus EP (difference, -4.5; 99% CI: -9.04, -0.04; nominal p = 0.009). Patients experienced longer TTD with durvalumab plus EP versus EP for all symptoms (hazard ratio [95% CI] for key symptoms: cough 0.78 [0.600‒1.026]; dyspnea 0.79 [0.625‒1.006]; chest pain 0.76 [0.575‒0.996]; fatigue 0.82 [0.653‒1.027]; appetite loss 0.70 [0.542‒0.899]), functioning, and global health status/QoL.
CONCLUSION
Addition of durvalumab to first-line EP maintained QoL and delayed worsening of patient-reported symptoms, functioning, and global health status/QoL compared with EP.
目的
在III期CASPIAN研究中，中期分析显示，对于广泛期小细胞肺癌（ES-SCLC）患者，一线度伐利尤单抗联合依托泊苷并与顺铂或卡铂（EP）联合使用，相较于单纯EP，显著改善了总生存期（主要终点）。在此，我们报告患者报告结局（PRO）。
材料与方法
初治的ES-SCLC患者每3周接受4个周期的度伐利尤单抗联合EP治疗，随后每4周接受度伐利尤单抗维持治疗直至疾病进展，或每3周接受6个周期的EP治疗。使用欧洲癌症研究与治疗组织（EORTC）生活质量问卷核心30（QLQ-C30）第3版及其肺癌模块生活质量问卷-肺癌13（QLQ-LC13）评估的PRO是预先设定的次要终点。采用重复测量混合模型分析从基线到疾病进展或12个月时预先设定的关键疾病相关症状（咳嗽、呼吸困难、胸痛、疲劳、食欲减退）的变化。分析了从随机分组开始症状、功能以及总体健康状况/生活质量（QoL）恶化的时间（TTD）。
结果
在度伐利尤单抗联合EP组和EP组中，分别有261例和260例患者可进行PRO评估。两组患者在12个月或直至疾病进展期间，关键症状的症状负担在数值上均有所减轻。在食欲减退方面，与基线相比的改善情况，两组间差异具有统计学意义，度伐利尤单抗联合EP组更具优势（差异为-4.5；99%CI：-9.04，-0.04；名义p = 0.009）。对于所有症状（关键症状的风险比[95%CI]：咳嗽0.78[0.600‒1.026]；呼吸困难0.79[0.625‒1.006]；胸痛0.76[0.575‒0.996]；疲劳0.82[0.653‒1.027]；食欲减退0.70[0.542‒0.899]）、功能以及总体健康状况/QoL，度伐利尤单抗联合EP组患者的TTD长于EP组。
结论
与EP相比，一线EP方案中加入度伐利尤单抗可维持QoL，并延迟患者报告的症状、功能以及总体健康状况/QoL的恶化。
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