老年患者术后曲妥珠＋化疗生活质量
对于HER2阳性早期乳腺癌，曲妥珠单抗＋化疗是术后全身辅助治疗的标准方案，疗效显著优于单用化疗。不过，对于难以耐受化疗的老年患者，单用曲妥珠单抗能否取代曲妥珠单抗＋化疗？2020年，美国临床肿瘤学会《临床肿瘤学杂志》发表日本全国乳腺癌术后辅助治疗研究协作组（N-SAS BC）RESPECT研究结果表明，HER2阳性早期乳腺癌老年患者术后单用曲妥珠单抗与曲妥珠单抗＋化疗相比，虽然3年无病生存（主要终点）未达非劣效，但是3年时平均生存时间相差<1个月、毒性反应发生率较低、健康相关生活质量较高，故对某些无法耐受化疗的老年患者，单用曲妥珠单抗可以作为术后辅助治疗选择之一。虽然术后辅助化疗对老年乳腺癌患者生活质量的不良影响显而易见，但是其程度和持续时间尚不明确。
RESPECT (NCT01104935): Evaluation of Trastuzumab Without Chemotherapy as a Postoperative Adjuvant Therapy in HER2 Positive Elderly Breast Cancer Patients: Randomized Controlled Trial (National Surgical Adjuvant Study of Breast Cancer: N-SAS BC 07)
2021年4月9日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表日本冈山大学医院、爱知癌症中心医院、国立国际医疗研究中心、埼玉红十字医院、鹿儿岛相良医院、东京癌症研究基金会有明医院、青森市立医院、静冈综合医院、龟田综合医院、筑波大学医院、北海道癌症中心、久留米综合医院、大阪市立大学医院、大阪国际癌症中心、京都足立医院、三重大学医院、熊本大学医院、中央大学医院、国立癌症研究中心东医院、东京大学医院的RESPECT研究二次分析报告，对HER2阳性乳腺癌老年患者术后曲妥珠单抗单药与曲妥珠单抗＋标准化疗的健康相关生活质量恶化程度和持续时间进行了比较。
该全国多中心非盲随机对照非劣效研究于2009年10月～2014年11月从日本全国99家医院入组年龄70～80岁的HER2阳性早期乳腺浸润癌术后患者275例（平均年龄73.5岁）按1∶1的比例随机分为两组：单用曲妥珠单抗137例或曲妥珠单抗＋化疗138例。治疗前和治疗开始后第2、12、36个月时，利用癌症治疗功能评定总表（FACT-G）、费城老年医学中心精神量表、医院焦虑和抑郁量表、患者神经毒性问卷、东京都健康长寿医疗研究中心活动能力指数对患者的生活质量进行评定。通过精确检验或混合模型重复测量对治疗前后个体变化进行比较。
结果，剔除其中治疗前退出研究和治疗前未完成生活质量问卷调查的35例患者，对其余231例（84%，平均年龄74岁）进行生活质量分析。
治疗前、治疗开始后第2、12、36个月时，231、198、177、178例患者完成生活质量问卷调查，FACT-G平均评分：
单用曲妥珠单抗组：78.9、80.4、82.7、79.1
曲妥珠单抗化疗组：79.5、74.5、78.4、78.5
单用曲妥珠单抗组与曲妥珠单抗化疗组相比，生活质量恶化（FACT-G评分比治疗前降低≥5分）比例：
2个月时较低：31%比48%（P=0.016）
12个月时较低：19%比38%（P=0.009）
36个月时相似：31%比36%（P=0.613）
单用曲妥珠单抗组与曲妥珠单抗化疗组相比：
2个月时医院焦虑和抑郁量表评分较低（P=0.003）
2个月时严重感觉周围神经病比例较低（P=0.001）
12个月时精神量表评分较高（P=0.024）
12个月时活动能力指数较高（P=0.042）
因此，该研究结果首次证实，HER2阳性早期乳腺癌老年患者术后曲妥珠单抗＋化疗对整体生活质量、精神和活动能力的不良影响至少持续1年，但是3年后未再发现，这些结果为寻求化疗联合曲妥珠单抗标准治疗的患者提供了信心。对于老年乳腺癌术后患者，进行抗HER2治疗＋辅助化疗时，需要提供至少1年的医疗支持和社会支持。
相关链接
J Clin Oncol. 2021 Apr 9. Online ahead of print.
Health-Related Quality of Life With Trastuzumab Monotherapy Versus Trastuzumab Plus Standard Chemotherapy as Adjuvant Therapy in Older Patients With HER2-Positive Breast Cancer.
Taira N, Sawaki M, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Ohashi Y, Mukai H, Kawahara T; RESPECT Study Group.
Okayama University Hospital, Okayama, Japan; Aichi Cancer Center Hospital, Nagoya, Japan; National Center for Global Health and Medicine, Tokyo, Japan; Japanese Red Cross Saitama Hospital, Saitama, Japan; Sagara Hospital, Kagoshima, Japan; The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan; Aomori City Hospital, Aomori, Japan; Shizuoka General Hospital, Shizuoka, Japan; Kameda Medical Center, Kamogawa, Japan; University of Tsukuba, Tsukuba, Japan; NHO Hokkaido Cancer Center, Sapporo, Japan; JCHO Kurume General Hospital, Kurume, Japan; Osaka City University Graduate School of Medicine, Osaka, Japan; Osaka International Cancer Institute, Osaka, Japan; Adachi Breast Clinic, Kyoto, Japan; Mie University Hospital, Tsu, Japan; Kumamoto University, Kumamoto, Japan; Chuo University, Tokyo, Japan; National Cancer Center Hospital East, Kashiwa, Japan; The University of Tokyo Hospital, Tokyo, Japan.
PURPOSE: We report findings on quality of life (QoL) in the RESPECT trial, which compared adjuvant trastuzumab monotherapy with trastuzumab plus chemotherapy in older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC).
PATIENTS AND METHODS: Patients age 70-80 years with human epidermal growth factor receptor 2-positive surgically treated breast cancer were randomly assigned to receive trastuzumab (T) or trastuzumab plus chemotherapy (T + C). QoL was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G), Philadelphia Geriatric Center Morale Scale, Hospital Anxiety and Depression Scale, Patient Neurotoxicity Questionnaire, and Tokyo Metropolitan Institute of Gerontology Index of Competence at baseline and after 2, 12, and 36 months. Comparisons were based on individual changes from baseline and were performed by Fisher's test or mixed-model repeated-measures.
RESULTS: Among 275 patients in the parent study, 231 (84%) (average age: 74 years) were included in the analysis. At 2, 12, and 36 months, 198, 177, and 178 patients completed surveys, and the mean FACT-G scores at each survey point were 78.9, 80.4, 82.7, and 79.1 in group T and 79.5, 74.5, 78.4, and 78.5 in group T + C. Compared with group T + C, the proportion of patients showing QoL deterioration (≥ 5 points decrease from baseline in FACT-G) was significantly lower at 2 months (31% v 48%; P = .016) and 12 months (19% v 38%; P = .009). In group T, the Hospital Anxiety and Depression Scale score (P = .003) and the proportion of severe sensory peripheral neuropathy (P = .001) were significantly lower at 2 months, and Philadelphia Geriatric Center Morale Scale and Tokyo Metropolitan Institute of Gerontology Index of Competence scores were significantly higher (P = .024, .042) at 12 months. At 36 months, there were no significant differences in any QoL items.
CONCLUSION: Detrimental effects of adjuvant chemotherapy on global QoL, morale, and activity capacity lasted for at least 12 months but were not observed at 36 months.
KEY OBJECTIVE: The adverse effects of adjuvant chemotherapy on quality of life (QoL) are clear, but knowledge of their extent and duration is limited, especially in older patients with breast cancer (BC). To our knowledge, our study is the first randomized controlled trial that focuses on the risks and benefits of chemotherapy in older patients with human epidermal growth factor receptor 2 (HER2)-positive BC, and we evaluated QoL in this trial.
KNOWLEDGE GENERATED: The addition of adjuvant chemotherapy to anti-HER2 therapy had a significant effect on global QoL, physical and functional well-being, morale, and activity capacity, and these effects persisted for at least 12 months. After 36 months, no detrimental effects of chemotherapy were observed in any of the evaluated QoL items.
RELEVANCE: These findings provide relief for patients seeking standard treatment with a combination of chemotherapy and trastuzumab. Care and social support for at least 1 year is required when adjuvant chemotherapy is given in addition to anti-HER2 therapy in older patients with BC.
PMID: 33835842
DOI: 10.1200/JCO.20.02751