Boyle Frances M, Smith Ian E, O'Shaughnessy Joyce, Ejlertsen Bent, Buzdar Aman U, Fumoleau Pierre, Gradishar William, Martin Miguel, Moy Beverly, Piccart-Gebhart Martine, Pritchard Kathleen I, Lindquist Deborah, Amonkar Mayur, Huang Yingjie, Rappold Erica, Williams Lisa S, Wang-Silvanto Jing, Kaneko Tomomi, Finkelstein Dianne M, Goss Paul E
Mater Hospital, Sydney, Australia.
Royal Marsden Hospital, London, UK.
Eur J Cancer. 2015 Apr;51(6):685-96. doi: 10.1016/j.ejca.2015.02.005. Epub 2015 Mar 6.
To evaluate health related quality of life (HRQOL) in TEACH, a phase III randomized placebo controlled trial of 12 months of adjuvant lapatinib in HER2 positive (HER2+) early breast cancer which demonstrated marginal benefit in disease-free survival.
Women on TEACH completed the Short Form 36-item health survey (version2; SF-36v2) at the baseline, six and 12 months after therapy initiation and six monthly thereafter. Mean changes were compared between treatment groups for two summary measures (Physical and Mental Component Summary scores; PCS and MCS) and eight domain measures (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health), and in patients discontinuing therapy. A five-point change was deemed a Minimally Clinically Important Difference (MCID). Response analysis compared the proportion of patients demonstrating a MCID in HRQOL, and a regression analysis identified predictors of worsening HRQOL.
3074 (97%) subjects completed baseline SF-36v2. During the initial 12 months, summary SF-36v2 scores decreased in both arms but did not reach Minimally Clinically Important Difference (MCID) despite significant incidences of diarrhoea and rash in lapatinib treated patients. At six months, women receiving lapatinib had more significant reductions (p < 0.01 versus placebo) in social functioning. Early treatment discontinuations were more frequent on lapatinib (32% versus 18%), and were associated with more substantial decrements of HRQOL in both arms. For those discontinuing primarily due to adverse events, decrements in HRQOL reached MCID in Mental Summary scores (MCS) only. Lower baseline HRQOL was a significant predictor of worsening HRQOL (p < 0.05).
Despite frequent but usually mild toxicities, adjuvant lapatinib is not associated with clinically significant decreases in overall HRQOL. These placebo-controlled results may also help to inform physicians and patients using lapatinib in metastatic HER2 positive breast cancer.
GlaxoSmithKline. The AVON Foundation NY supported PEG, DF and BM and The Friends of the Mater Foundation supported FB.
在TEACH研究中评估健康相关生活质量（HRQOL），这是一项III期随机安慰剂对照试验，对HER2阳性（HER2+）早期乳腺癌患者进行12个月的辅助拉帕替尼治疗，该试验在无病生存期显示出边际效益。
TEACH研究中的女性患者在基线、治疗开始后6个月和12个月以及此后每6个月完成36项简短健康调查（第2版；SF-36v2）。比较治疗组之间两个汇总指标（身体和心理成分汇总得分；PCS和MCS）以及八个领域指标（身体功能、角色身体、身体疼痛、总体健康、活力、社会功能、角色情感和心理健康）的平均变化，以及中断治疗的患者的变化。五分的变化被视为最小临床重要差异（MCID）。反应分析比较了HRQOL中显示MCID的患者比例，回归分析确定了HRQOL恶化的预测因素。
3074名（97%）受试者完成了基线SF-36v2。在最初的12个月中，两组的SF-36v2汇总得分均下降，但尽管拉帕替尼治疗的患者腹泻和皮疹发生率较高，但未达到最小临床重要差异（MCID）。在6个月时，接受拉帕替尼治疗的女性社会功能下降更为显著（与安慰剂相比，p<0.01）。拉帕替尼组早期治疗中断更为频繁（32%对18%），并且两组的HRQOL下降幅度更大。对于主要因不良事件而中断治疗的患者，HRQOL下降仅在心理汇总得分（MCS）中达到MCID。较低的基线HRQOL是HRQOL恶化的显著预测因素（p<0.05）。
尽管毒性频繁但通常较轻，辅助拉帕替尼治疗与总体HRQOL的临床显著下降无关。这些安慰剂对照结果也可能有助于为使用拉帕替尼治疗转移性HER2阳性乳腺癌的医生和患者提供信息。
葛兰素史克公司。纽约雅芳基金会支持PEG、DF和BM，马特之友基金会支持FB。
