Chemotherapy for advanced non-small cell lung cancer in the elderly population

Santos Fábio Nasser; Castria Tiago Biachi de; Cruz Marcelo Rocha Souza; Riera Rachel

摘要

ABSTRACT BACKGROUND: Approximately 50% of patients with newly diagnosed non-small cell lung cancer (NSCLC) are over 70 years of age at diagnosis. Despite this fact, these patients are underrepresented in randomized controlled trials (RCTs). As a consequence, the most appropriate regimens for these patients are controversial, and the role of single-agent or combination therapy is unclear. In this setting, a critical systematic review of RCTs in this group of patients is warranted. OBJECTIVES: To assess the effectiveness and safety of different cytotoxic chemotherapy regimens for previously untreated elderly patients with advanced (stage IIIB and IV) NSCLC. To also assess the impact of cytotoxic chemotherapy on quality of life. METHODS: Search methods: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE (1966 to 31 October 2014), EMBASE (1974 to 31 October 2014), and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 31 October 2014). In addition, we handsearched the proceedings of major conferences, reference lists from relevant resources, and the ClinicalTrial.gov database. Selection criteria: We included only RCTs that compared non-platinum single-agent therapy versus non-platinum combination therapy, or non-platinum therapy versus platinum combination therapy in patients over 70 years of age with advanced NSCLC. We allowed inclusion of RCTs specifically designed for the elderly population and those designed for elderly subgroup analyses. Data collection and analysis: Two review authors independently assessed search results, and a third review author resolved disagreements. We analyzed the following endpoints: overall survival (OS), one-year survival rate (1yOS), progression-free survival (PFS), objective response rate (ORR), major adverse events, and quality of life (QoL). MAIN RESULTS: We included 51 trials in the review: non-platinum single-agent therapy versus non-platinum combination therapy (seven trials) and non-platinum combination therapy versus platinum combination therapy (44 trials). Non-platinum single-agent versus non-platinum combination therapy Low-quality evidence suggests that these treatments have similar effects on overall survival (hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.72 to 1.17; participants = 1062; five RCTs), 1yOS (risk ratio (RR) 0.88, 95% CI 0.73 to 1.07; participants = 992; four RCTs), and PFS (HR 0.94, 95% CI 0.83 to 1.07; participants = 942; four RCTs). Non-platinum combination therapy may better improve ORR compared with non-platinum single-agent therapy (RR 1.79, 95% CI 1.41 to 2.26; participants = 1014; five RCTs; low-quality evidence). Differences in effects on major adverse events between treatment groups were as follows: anemia: RR 1.10, 95% 0.53 to 2.31; participants = 983; four RCTs; very low-quality evidence; neutropenia: RR 1.26, 95% CI 0.96 to 1.65; participants = 983; four RCTs; low-quality evidence; and thrombocytopenia: RR 1.45, 95% CI 0.73 to 2.89; participants = 914; three RCTs; very low-quality evidence. Only two RCTs assessed quality of life; however, we were unable to perform a meta-analysis because of the paucity of available data. Non-platinum therapy versus platinum combination therapy Platinum combination therapy probably improves OS (HR 0.76, 95% CI 0.69 to 0.85; participants = 1705; 13 RCTs; moderate-quality evidence), 1yOS (RR 0.89, 95% CI 0.82 to 0.96; participants = 813; 13 RCTs; moderate-quality evidence), and ORR (RR 1.57, 95% CI 1.32 to 1.85; participants = 1432; 11 RCTs; moderate-quality evidence) compared with non-platinum therapies. Platinum combination therapy may also improve PFS, although our confidence in this finding is limited because the quality of evidence was low (HR 0.76, 95% CI 0.61 to 0.93; participants = 1273; nine RCTs). Effects on major adverse events between treatment groups were as follows: anemia: RR 2.53, 95% CI 1.70 to 3.76; participants = 1437; 11 RCTs; low-quality evidence; thrombocytopenia: RR 3.59, 95% CI 2.22 to 5.82; participants = 1260; nine RCTs; low-quality evidence; fatigue: RR 1.56, 95% CI 1.02 to 2.38; participants = 1150; seven RCTs; emesis: RR 3.64, 95% CI 1.82 to 7.29; participants = 1193; eight RCTs; and peripheral neuropathy: RR 7.02, 95% CI 2.42 to 20.41; participants = 776; five RCTs; low-quality evidence. Only five RCTs assessed QoL; however, we were unable to perform a meta-analysis because of the paucity of available data. AUTHORS' CONCLUSIONS: In people over the age of 70 with advanced NSCLC who do not have significant co-morbidities, increased survival with platinum combination therapy needs to be balanced against higher risk of major adverse events when compared with non-platinum therapy. For people who are not suitable candidates for platinum treatment, we have found low-quality evidence suggesting that non-platinum combination and single-agent therapy regimens have similar effects on

机译：摘要背景：大约50％的新诊断的非小细胞肺癌（NSCLC）患者在诊断时年龄超过70岁。尽管有这个事实，但这些患者在随机对照试验（RCT）中的代表性不足。结果，对于这些患者最合适的方案存在争议，并且单药或联合治疗的作用尚不清楚。在这种情况下，有必要对这一组患者进行严格的RCT系统评价。目的：评估不同细胞毒性化疗方案对先前未经治疗的晚期（IIIB和IV期）NSCLC老年患者的有效性和安全性。还要评估细胞毒性化疗对生活质量的影响。方法：搜索方法：我们搜索了以下电子数据库：Cochrane对照试验中央登记册（中央; 2014年，第10期），MEDLINE（1966年至2014年10月31日），EMBASE（1974年至2014年10月31日）和拉丁美洲加勒比海地区健康科学文献（LILACS）（1982年至2014年10月31日）。此外，我们还手动搜索了主要会议的会议记录，相关资源的参考文献列表以及ClinicalTrial.gov数据库。选择标准：我们仅纳入了比较70岁以上晚期NSCLC患者中非铂类单药治疗与非铂类联合治疗或非铂类治疗与铂类联合治疗的RCT。我们允许纳入专门针对老年人群的RCT和针对老年人亚组分析的RCT。数据收集和分析：两位评论作者独立评估搜索结果，而第三位评论作者解决了分歧。我们分析了以下终点：总体生存期（OS），一年生存率（1yOS），无进展生存期（PFS），客观缓解率（ORR），主要不良事件和生活质量（QoL）。主要结果：我们纳入了51项试验：非铂单药治疗与非铂联合治疗（七项试验）和非铂联合治疗与铂联合治疗（44项试验）。非铂单药与非铂联合疗法低质量证据表明，这些疗法对总体生存率具有相似的影响（危险比（HR）0.92，95％置信区间（CI）0.72至1.17;参与者= 1062;五个RCT），1yOS（风险比（RR）0.88，95％CI 0.73至1.07;参与者= 992;四个RCT）和PFS（HR 0.94，95％CI 0.83至1.07;参与者= 942;四个RCT）。与非铂单药疗法相比，非铂联合疗法可能更好地改善ORR（RR 1.79，95％CI 1.41至2.26;参与者= 1014;五个RCT;低质量证据）。治疗组之间对主要不良事件的影响差异如下：贫血：RR 1.10，95％0.53至2.31;参与者= 983;四个RCT;证据质量很差;中性粒细胞减少症：RR 1.26，95％CI 0.96至1.65;参与者= 983;四个RCT;低质量的证据;血小板减少症：RR 1.45，95％CI 0.73至2.89;参与者= 914;三个RCT;质量很差的证据。只有两个RCT评估了生活质量。但是，由于缺乏可用数据，我们无法执行荟萃分析。非铂疗法与铂类联合疗法铂类联合疗法可能会改善OS（HR 0.76，95％CI 0.69至0.85;参与者= 1705; 13个RCT;中等质量的证据），1yOS（RR 0.89，95％CI 0.82至0.96; RR = 0.85，CI为0.96）。与非铂疗法相比，参与者= 813; 13个RCT;中等质量的证据）和ORR（RR 1.57，95％CI 1.32至1.85;参与者= 1432; 11个RCT;中等质量的证据）。铂类联合疗法也可能改善PFS，尽管由于证据质量低（HR 0.76，95％CI 0.61至0.93;参与者= 1273; 9个RCT），我们对这一发现的信心有限。治疗组之间对主要不良事件的影响如下：贫血：RR 2.53，95％CI 1.70至3.76;参与者= 1437; 11个RCT;低质量的证据;血小板减少症：RR 3.59，95％CI 2.22至5.82;参与者= 1260;九个RCT;低质量的证据;疲劳：RR 1.56，95％CI 1.02至2.38;参与者= 1150;七个RCT;呕吐：RR 3.64，95％CI 1.82至7.29;参与者= 1193;八个RCT;和周围神经病变：RR 7.02，95％CI 2.42至20.41;参与者= 776;五个RCT;低质量的证据。只有五个RCT评估了生活质量。但是，由于缺乏可用数据，我们无法执行荟萃分析。作者的结论：对于70岁以上晚期NSCLC并没有明显合并症的人，与非铂疗法相比，铂类联合疗法的生存率增加与重大不良事件的高风险之间需要取得平衡。对于不适合铂类治疗的人，我们发现低质量的证据表明，非铂类联合治疗和单药治疗方案对铂类药物的治疗效果相似。

Chemotherapy for advanced non-small cell lung cancer in the elderly population

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