Department of Gynecology and Gynecological Oncology, Medical University of Vienna, Vienna, Austria.
Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria.
J Clin Oncol. 2023 Nov 20;41(33):5118-5130. doi: 10.1200/JCO.23.00126. Epub 2023 Aug 9.
BMI affects breast cancer risk and prognosis. In contrast to cytotoxic chemotherapy, CDK4/6 inhibitors are given at a fixed dose, irrespective of BMI or weight. This preplanned analysis of the global randomized PALLAS trial investigates the impact of BMI on the side-effect profile, treatment adherence, and efficacy of palbociclib.
Patients were categorized at baseline according to WHO BMI categories. Neutropenia rates were assessed with univariable and multivariable logistic regression. Time to early discontinuation of palbociclib was analyzed with Fine and Gray competing risk models. Unstratified Cox models were used to investigate the association between BMI category and time to invasive disease-free survival (iDFS). 95% CIs were derived.
Of 5,698 patients included in this analysis, 68 (1.2%) were underweight, 2,082 (36.5%) normal weight, 1,818 (31.9%) overweight, and 1,730 (30.4%) obese at baseline. In the palbociclib arm, higher BMI was associated with a significant decrease in neutropenia (unadjusted odds ratio for 1-unit change, 0.93; 95% CI, 0.91 to 0.94; adjusted for age, race ethnicity, region, chemotherapy use, and Eastern Cooperative Oncology Group at baseline, 0.93; 95% CI, 0.92 to 0.95). This translated into a significant decrease in treatment discontinuation rate with higher BMI (adjusted hazard ratio [HR] for 10-unit change, 0.75; 95% CI, 0.67 to 0.83). There was no significant improvement in iDFS with the addition of palbociclib to ET in any weight category (normal weight HR, 0.84; 95% CI, 0.63 to 1.12; overweight HR, 1.10; 95% CI, 0.82 to 1.49; and obese HR, 0.95; 95% CI, 0.69 to 1.30) in this analysis early in follow-up (31 months).
This preplanned analysis of the PALLAS trial demonstrates a significant impact of BMI on side effects, dose reductions, early treatment discontinuation, and relative dose intensity. Additional long-term follow-up will further evaluate whether BMI ultimately affects outcome.
BMI 会影响乳腺癌的风险和预后。与细胞毒性化疗不同，CDK4/6 抑制剂是按照固定剂量给药的，而与 BMI 或体重无关。这项针对全球随机 PALLAS 试验的预先计划分析调查了 BMI 对帕博西尼的副作用谱、治疗依从性和疗效的影响。
根据世界卫生组织 BMI 类别，患者在基线时进行分类。使用单变量和多变量逻辑回归评估中性粒细胞减少症的发生率。使用 Fine 和 Gray 竞争风险模型分析早期停用帕博西尼的时间。使用未分层的 Cox 模型研究 BMI 类别与无侵袭性疾病无进展生存（iDFS）时间之间的关联。
在本分析中纳入的 5698 例患者中，68 例（1.2%）体重不足，2082 例（36.5%）体重正常，1818 例（31.9%）超重，1730 例（30.4%）肥胖。在帕博西尼组中，较高的 BMI 与中性粒细胞减少症显著降低相关（1 个单位变化的未调整优势比为 0.93；95%CI，0.91 至 0.94；调整年龄、种族、区域、化疗使用和基线时的东部合作肿瘤学组后，0.93；95%CI，0.92 至 0.95）。这导致较高 BMI 组的治疗停药率显著降低（10 个单位变化的调整后危害比，0.75；95%CI，0.67 至 0.83）。在任何体重类别中，与 ET 联合使用帕博西尼均未显著改善 iDFS（体重正常的 HR，0.84；95%CI，0.63 至 1.12；超重的 HR，1.10；95%CI，0.82 至 1.49；肥胖的 HR，0.95；95%CI，0.69 至 1.30），这是在随访早期（31 个月）进行的这项 PALLAS 试验的预先计划分析。
这项 PALLAS 试验的预先计划分析表明，BMI 对副作用、剂量减少、早期治疗停药和相对剂量强度有显著影响。额外的长期随访将进一步评估 BMI 是否最终影响结局。
