Department of Medical Oncology, Breast Cancer Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
J Clin Oncol. 2021 Jun 20;39(18):2005-2015. doi: 10.1200/JCO.20.01139. Epub 2021 Mar 29.
In the phase III SOLAR-1 trial (NCT02437318), the PI3Kα-selective inhibitor and degrader alpelisib significantly improved median progression-free survival when added to fulvestrant in patients with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha ()-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. We assessed health-related quality of life using patient-reported outcome measures in these patients.
In the -mutant cohort, 341 patients were randomly assigned 1:1 to receive alpelisib 300 mg daily or placebo plus fulvestrant 500 mg on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day cycles. Patient-reported outcomes were evaluated with the European Organisation for Research and Treatment of Cancer QoL of Cancer Patients and Brief Pain Inventory-Short Form questionnaires. Changes from baseline and time to 10% deterioration were analyzed using repeated measurement models and Cox models, respectively.
Global Health Status/QoL and functional status were maintained from baseline (mean changes < 10 points) in the alpelisib (overall change from baseline [95% CI], -3.50 [-8.02 to 1.02]) and placebo arms (overall change from baseline [95% CI], 0.27 [-4.48 to 5.02]). Overall treatment effect in Global Health Status/QoL was not significantly different between arms (-3.77; 95% CI, -8.35 to 0.80; = .101). Time to 10% deterioration for Global Health Status/QoL was similar between arms (hazard ratio, 1.03; 95% CI, 0.72 to 1.48). Compared with placebo, deterioration in social functioning and in diarrhea, appetite loss, nausea or vomiting, and fatigue symptom subscales occurred with alpelisib. Numerical improvement in Worst Pain was observed with alpelisib versus placebo (42% 32%, week 24; = .090).
In SOLAR-1, there was no statistical difference in deterioration of Global Health Status/QoL between arms, whereas symptom subscales favored placebo for diarrhea, appetite loss, nausea or vomiting, and fatigue, known side effects of alpelisib. Treatment decisions must consider efficacy and tolerability; taken with clinical efficacy, these results support the benefit-risk profile of alpelisib in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative -mutated advanced breast cancer.
在 III 期 SOLAR-1 试验（NCT02437318）中，PI3Kα 选择性抑制剂和降解剂阿培利司与氟维司群联合应用于磷酸肌醇-4,5-二磷酸 3-激酶催化亚单位 α（PIK3CA）突变、激素受体阳性、人表皮生长因子受体 2 阴性的晚期乳腺癌患者，显著改善了中位无进展生存期。我们使用患者报告的结局测量评估了这些患者的健康相关生活质量。
在突变亚组中，341 例患者随机分为 1:1 组，分别接受阿培利司 300 mg 每日或安慰剂联合氟维司群 500 mg 第 1 天和第 15 天，随后每 28 天周期第 1 天。使用欧洲癌症研究与治疗组织生活质量问卷和简明疼痛量表-短表评估患者报告的结果。使用重复测量模型和 Cox 模型分别分析基线和 10%恶化的时间变化。
在阿培利司（总体变化自基线[95%CI]，-3.50[-8.02 至 1.02]）和安慰剂组中，全球健康状况/生活质量和功能状态均自基线保持稳定（平均变化<10 分）（总体变化自基线[95%CI]，0.27[-4.48 至 5.02]）。两组之间的全球健康状况/生活质量总体治疗效果无显著差异（-3.77；95%CI，-8.35 至 0.80；=0.101）。全球健康状况/生活质量恶化的时间在两组之间相似（危险比，1.03；95%CI，0.72 至 1.48）。与安慰剂相比，阿培利司治疗后社会功能以及腹泻、食欲减退、恶心或呕吐和疲劳症状亚量表恶化。与安慰剂相比，阿培利司治疗后最差疼痛的数值改善（第 24 周时，42%比 32%；=0.090）。
在 SOLAR-1 中，两组之间全球健康状况/生活质量恶化没有统计学差异，而腹泻、食欲减退、恶心或呕吐和疲劳症状亚量表对安慰剂有利，这是阿培利司已知的副作用。治疗决策必须考虑疗效和耐受性；与临床疗效结合考虑，这些结果支持阿培利司在激素受体阳性、人表皮生长因子受体 2 阴性、PIK3CA 突变的晚期乳腺癌患者中的获益风险特征。
