A Comparative Study Evaluating the Quality of Life and Survival Outcomes in Patients Receiving Chemotherapy Versus Oral Tyrosine Kinase Inhibitor in the Third Line and Beyond Setting for Advanced NSCLC

IF 3 Q2 ONCOLOGY
Vanita Noronha MBBS, MD, DM , Nandini S. Menon MBBS, MD, DrNB , Vijay Maruti Patil MBBS, MD, DM , M.V. Chandrakanth MBBS, MD, DM , Sucheta More BAMS, MSc , Aditya Dhanawat MBBS, MD , Oindrila Roy Chowdhary MSc , Ajaykumar Chandrabhan Singh MBBS, MD, DM , Supriya Goud BAMS, PGDCR , Srushti Shah BHMS, PGDCR , Naveen Karuvandan MBBS, MD, DM , Kunal Naishadh Jobanputra MBBS, MD, DM , Darshit Kalpeshkumar Shah DM , Minit Jalan Shah MBBS, MD, DM , Rupjyoti Sarma MBBS, MD, DM , Dhwaniben Patel MBBS, MD , Ritam Joarder MBBS, MD , Prashant Kumar MBBS, MD , Anupa John MBBS, MD , Jaspreet Kaur MBBS, MD , Kumar Prabhash MBBS, MD, DM
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Chandrakanth MBBS, MD, DM ,&nbsp;Sucheta More BAMS, MSc ,&nbsp;Aditya Dhanawat MBBS, MD ,&nbsp;Oindrila Roy Chowdhary MSc ,&nbsp;Ajaykumar Chandrabhan Singh MBBS, MD, DM ,&nbsp;Supriya Goud BAMS, PGDCR ,&nbsp;Srushti Shah BHMS, PGDCR ,&nbsp;Naveen Karuvandan MBBS, MD, DM ,&nbsp;Kunal Naishadh Jobanputra MBBS, MD, DM ,&nbsp;Darshit Kalpeshkumar Shah DM ,&nbsp;Minit Jalan Shah MBBS, MD, DM ,&nbsp;Rupjyoti Sarma MBBS, MD, DM ,&nbsp;Dhwaniben Patel MBBS, MD ,&nbsp;Ritam Joarder MBBS, MD ,&nbsp;Prashant Kumar MBBS, MD ,&nbsp;Anupa John MBBS, MD ,&nbsp;Jaspreet Kaur MBBS, MD ,&nbsp;Kumar Prabhash MBBS, MD, DM","doi":"10.1016/j.jtocrr.2023.100622","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>The outcomes in advanced NSCLC have improved owing to the availability of more effective systemic and improved supportive care. This has increased the number of patients who seek treatment in the third line and beyond setting. We conducted this study to compare the quality of life (QoL), toxicity, and outcomes in patients receiving chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) in this setting.</p></div><div><h3>Methods</h3><p>In this phase 3, randomized, open-label study, patients with stage III or IV NSCLC with disease progression on at least two prior lines of chemotherapy, with a life expectancy of at least 3 months, without prior EGFR TKI exposure, and stable brain metastases (if any) were included. Patients were randomized to receive chemotherapy (gemcitabine or docetaxel or paclitaxel or vinorelbine) or an EGFR TKI (erlotinib or gefitinib). The primary end point was the change in QoL at 8 to 10 weeks; the secondary outcomes were safety and overall survival (OS). Patients underwent clinical evaluation at every visit, and toxicity was assessed as per Common Terminology Criteria for Adverse Events version 4.03. A radiological tumor response assessment was done every 8 to 12 weeks from the start of therapy. The QoL was assessed using the EORTC QLQ C30 and LC13 questionnaires. The change in QoL scores was calculated as the difference between scores at baseline and scores at 8 to 10 weeks (Δ) for each QoL domain. The Mann-Whitney <em>U</em> test was used to compare the mean difference (Δ) for each domain. OS and progression-free survival (PFS) were determined using the Kaplan-Meier method and Cox proportional regression analysis.</p></div><div><h3>Results</h3><p>A total of 246 patients were enrolled in the study, with 123 in each arm. There was a male predominance with 69.1% male patients in the chemotherapy arm and 70.7% in the EGFR TKI arm. The median age of patients in the chemotherapy arm was 54 years and 55 years in the chemotherapy and EGFR TKI arms, respectively. There was no significant difference in the change in QoL at baseline and the second visit (Δ) in both arms in all domains of EORTC QLQ C30 except cognitive function (<em>p</em> = 0.0045) and LC13 except alopecia (0.01249). The mean Δ Global Health Status was −28 in the chemotherapy arm and −26.8 in the EGFR TKI arm; this was not statistically significant (<em>p</em> = 0.973). The median follow-up was 88.1 months (95% confidence interval [CI]: 39.04–137.15). On the intention-to-treat analysis, the median PFS was 3.13 months (95% CI: 2.15–4.11) in the chemotherapy arm and 2.26 months (95% CI: 2.1–2.43) in the EGFR TKI arm, with hazard ratio at 1.074 (95% CI: 0.83–1.38) (<em>p</em> = 0.58). There were 120 deaths in each arm. The median OS was 7.63 months (95% CI: 5.96–9.30) in the chemotherapy arm and 7.5 months in the EGFR TKI arm (95% CI: 5.85–9.14); hazard ratio at 1.033 (95% CI: 0.80–1.33) (<em>p</em> = 0.805). The toxicity profile was similar in both arms except for a significantly higher incidence of fatigue (<em>p</em> = 0.043), peripheral neuropathy (0.000), alopecia, hypokalemia (0.037), and pedal edema (0.007) in the chemotherapy arm and dry skin (<em>p</em> = 0.000) and skin rash (<em>p</em> = 0.019) in the EGFR TKI arm.</p></div><div><h3>Conclusions</h3><p>There was no significant difference in most QoL scales (except cognitive function and alopecia), OS, and PFS of patients with advanced NSCLC receiving an EGFR TKI as compared with chemotherapy TKI in the third-line setting. 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引用次数: 0

Abstract

Introduction

The outcomes in advanced NSCLC have improved owing to the availability of more effective systemic and improved supportive care. This has increased the number of patients who seek treatment in the third line and beyond setting. We conducted this study to compare the quality of life (QoL), toxicity, and outcomes in patients receiving chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) in this setting.

Methods

In this phase 3, randomized, open-label study, patients with stage III or IV NSCLC with disease progression on at least two prior lines of chemotherapy, with a life expectancy of at least 3 months, without prior EGFR TKI exposure, and stable brain metastases (if any) were included. Patients were randomized to receive chemotherapy (gemcitabine or docetaxel or paclitaxel or vinorelbine) or an EGFR TKI (erlotinib or gefitinib). The primary end point was the change in QoL at 8 to 10 weeks; the secondary outcomes were safety and overall survival (OS). Patients underwent clinical evaluation at every visit, and toxicity was assessed as per Common Terminology Criteria for Adverse Events version 4.03. A radiological tumor response assessment was done every 8 to 12 weeks from the start of therapy. The QoL was assessed using the EORTC QLQ C30 and LC13 questionnaires. The change in QoL scores was calculated as the difference between scores at baseline and scores at 8 to 10 weeks (Δ) for each QoL domain. The Mann-Whitney U test was used to compare the mean difference (Δ) for each domain. OS and progression-free survival (PFS) were determined using the Kaplan-Meier method and Cox proportional regression analysis.

Results

A total of 246 patients were enrolled in the study, with 123 in each arm. There was a male predominance with 69.1% male patients in the chemotherapy arm and 70.7% in the EGFR TKI arm. The median age of patients in the chemotherapy arm was 54 years and 55 years in the chemotherapy and EGFR TKI arms, respectively. There was no significant difference in the change in QoL at baseline and the second visit (Δ) in both arms in all domains of EORTC QLQ C30 except cognitive function (p = 0.0045) and LC13 except alopecia (0.01249). The mean Δ Global Health Status was −28 in the chemotherapy arm and −26.8 in the EGFR TKI arm; this was not statistically significant (p = 0.973). The median follow-up was 88.1 months (95% confidence interval [CI]: 39.04–137.15). On the intention-to-treat analysis, the median PFS was 3.13 months (95% CI: 2.15–4.11) in the chemotherapy arm and 2.26 months (95% CI: 2.1–2.43) in the EGFR TKI arm, with hazard ratio at 1.074 (95% CI: 0.83–1.38) (p = 0.58). There were 120 deaths in each arm. The median OS was 7.63 months (95% CI: 5.96–9.30) in the chemotherapy arm and 7.5 months in the EGFR TKI arm (95% CI: 5.85–9.14); hazard ratio at 1.033 (95% CI: 0.80–1.33) (p = 0.805). The toxicity profile was similar in both arms except for a significantly higher incidence of fatigue (p = 0.043), peripheral neuropathy (0.000), alopecia, hypokalemia (0.037), and pedal edema (0.007) in the chemotherapy arm and dry skin (p = 0.000) and skin rash (p = 0.019) in the EGFR TKI arm.

Conclusions

There was no significant difference in most QoL scales (except cognitive function and alopecia), OS, and PFS of patients with advanced NSCLC receiving an EGFR TKI as compared with chemotherapy TKI in the third-line setting. The toxicity profile is consistent with the known toxicities of the agents.

晚期非小细胞肺癌三线及三线以上治疗中化疗与口服酪氨酸激酶抑制剂对患者生活质量和生存结果的比较评估研究
导言:由于有了更有效的系统疗法和更好的支持性治疗,晚期 NSCLC 的治疗效果有所改善。因此,寻求三线及三线以上治疗的患者人数有所增加。在这项三期随机开放标签研究中,我们纳入了既往接受过至少两线化疗且疾病进展的 III 或 IV 期 NSCLC 患者,他们的预期寿命至少为 3 个月,既往未接受过 EGFR 酪氨酸激酶抑制剂(TKIs)治疗,且脑转移情况稳定(如有)。患者随机接受化疗(吉西他滨或多西他赛或紫杉醇或维诺雷宾)或EGFR TKI(厄洛替尼或吉非替尼)。主要终点是8至10周后的QoL变化;次要终点是安全性和总生存期(OS)。患者每次就诊都要接受临床评估,并根据《不良事件通用术语标准》4.03版评估毒性。自治疗开始起,每8至12周进行一次肿瘤放射学反应评估。QoL 采用 EORTC QLQ C30 和 LC13 问卷进行评估。QoL评分的变化以基线评分与8至10周时各QoL领域评分的差值(Δ)计算。Mann-Whitney U 检验用于比较每个领域的平均差异 (Δ)。采用 Kaplan-Meier 法和 Cox 比例回归分析确定 OS 和无进展生存期 (PFS)。化疗组男性患者占69.1%,EGFR TKI组男性患者占70.7%,男性患者占多数。化疗组和 EGFR TKI 治疗组患者的中位年龄分别为 54 岁和 55 岁。除认知功能(p = 0.0045)和LC13(脱发除外)(0.01249)外,两组患者在EORTC QLQ C30所有领域的基线和第二次就诊时(Δ)的QoL变化均无明显差异。化疗组的平均Δ总体健康状况为-28,EGFR TKI治疗组为-26.8;差异无统计学意义(p = 0.973)。中位随访时间为 88.1 个月(95% 置信区间 [CI]:39.04-137.15)。根据意向治疗分析,化疗组的中位 PFS 为 3.13 个月(95% CI:2.15-4.11),EGFR TKI 组为 2.26 个月(95% CI:2.1-2.43),危险比为 1.074(95% CI:0.83-1.38)(p = 0.58)。两组各有120例死亡病例。化疗组的中位OS为7.63个月(95% CI:5.96-9.30),EGFR TKI组为7.5个月(95% CI:5.85-9.14);危险比为1.033(95% CI:0.80-1.33)(p = 0.805)。除了化疗组的疲劳(p = 0.043)、周围神经病变(0.000)、脱发、低钾血症(0.037)和足底水肿(0.007)发生率显著高于EGFR治疗组,以及皮肤干燥(p = 0.000)和皮疹(p = 0.结论在三线治疗中,晚期 NSCLC 患者接受 EGFR TKI 与化疗 TKI 相比,在大多数 QoL 量表(认知功能和脱发除外)、OS 和 PFS 方面没有显著差异。其毒性与已知药物的毒性一致。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.20
自引率
0.00%
发文量
145
审稿时长
19 weeks
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