College of Medicine and Public Health, Flinders Medical Centre, Flinders University, Bedford Park, Adelaide, SA, Australia.
AdventHealth Cancer Institute, Orlando, FL, USA.
BMC Cancer. 2024 Mar 25;24(1):379. doi: 10.1186/s12885-024-12132-w.
Multiple studies have indicated that patients with high body mass index (BMI) may have favourable survival outcomes following treatment with an immune checkpoint inhibitor (ICI). However, this evidence is limited by several factors, notably the minimal evidence from randomised controlled trials (RCTs), the use of categorised BMI with inconsistent cut point definitions, and minimal investigation of contemporary combination ICI therapy. Moreover, whether overweight and obese patients gain a larger benefit from contemporary frontline chemoimmunotherapy in non-small cell lung cancer (NSCLC) is unclear.
This secondary analysis pooled individual patient data from the intention-to-treat population of the IMpower130 and IMpower150 RCTs comparing chemoimmunotherapy versus chemotherapy. Co-primary outcomes were overall survival (OS) and progression-free survival (PFS). The potentially non-linear relationship between BMI and chemoimmunotherapy treatment effect was evaluated using Multivariable Fractional Polynomial Interaction (MFPI). As a sensitivity analysis, chemoimmunotherapy treatment effect (chemoimmunotherapy versus chemotherapy) on survival was also estimated for each BMI subgroup defined by World Health Organisation classification. Exploratory analyses in the respective chemoimmunotherapy and chemotherapy cohort were undertaken to examine the survival outcomes among BMI subgroups.
A total of 1282 patients were included. From the MFPI analysis, BMI was not significantly associated with chemoimmunotherapy treatment effect with respect to either OS (p = 0.71) or PFS (p = 0.35). This was supported by the sensitivity analyses that demonstrated no significant treatment effect improvement in OS/PFS among overweight or obese patients compared to normal weight patients (OS: normal BMI HR = 0.74 95% CI 0.59-0.93, overweight HR = 0.78 95% CI 0.61-1.01, obese HR = 0.84 95% CI 0.59-1.20). Exploratory analyses further highlighted that survival outcomes were not significantly different across BMI subgroups in either the chemoimmunotherapy therapy cohort (Median OS: normal BMI 19.9 months, overweight 17.9 months, and obese 19.5 months, p = 0.7) or the chemotherapy cohort (Median OS: normal 14.1 months, overweight 15.9 months, and obese 16.7 months, p = 0.7).
There was no association between high BMI (overweight or obese individuals) and enhanced chemoimmunotherapy treatment benefit in front-line treatment of advanced non-squamous NSCLC. This contrasts with previous publications that showed a superior treatment benefit in overweight and obese patients treated with immunotherapy given without chemotherapy.
多项研究表明，接受免疫检查点抑制剂（ICI）治疗的高体重指数（BMI）患者可能有更好的生存结果。然而，这一证据受到多种因素的限制，尤其是随机对照试验（RCT）的证据有限、使用分类 BMI 且不一致的切点定义，以及对当代联合 ICI 治疗的研究不足。此外，超重和肥胖患者在非小细胞肺癌（NSCLC）的非一线化疗免疫治疗中是否能获得更大的获益尚不清楚。
本二次分析汇总了比较化疗免疫治疗与化疗的 IMpower130 和 IMpower150 RCT 意向治疗人群的个体患者数据。主要终点为总生存期（OS）和无进展生存期（PFS）。使用多变量分数多项式交互（MFPI）评估 BMI 与化疗免疫治疗治疗效果之间的潜在非线性关系。作为敏感性分析，还根据世界卫生组织（WHO）分类定义的 BMI 亚组，估计了 BMI 对每种治疗的治疗效果（化疗免疫治疗与化疗）对生存的影响。在相应的化疗免疫治疗和化疗队列中进行了探索性分析，以检查 BMI 亚组的生存结果。
共纳入 1282 例患者。从 MFPI 分析来看，BMI 与 OS（p=0.71）或 PFS（p=0.35）的化疗免疫治疗治疗效果均无显著相关性。敏感性分析也支持了这一结果，与正常体重患者相比，超重或肥胖患者的 OS/PFS 无显著治疗效果改善（OS：正常 BMI HR=0.74，95%CI 0.59-0.93，超重 HR=0.78，95%CI 0.61-1.01，肥胖 HR=0.84，95%CI 0.59-1.20）。进一步的探索性分析还强调，在化疗免疫治疗组（中位 OS：正常 BMI 19.9 个月，超重 17.9 个月，肥胖 19.5 个月，p=0.7）或化疗组（中位 OS：正常 BMI 14.1 个月，超重 15.9 个月，肥胖 16.7 个月，p=0.7）中，BMI 亚组之间的生存结果无显著差异。
在晚期非鳞状 NSCLC 的一线治疗中，高 BMI（超重或肥胖）与增强化疗免疫治疗的疗效无相关性。这与之前的研究结果相反，之前的研究表明，在不联合化疗的情况下，接受免疫治疗的超重和肥胖患者的治疗获益更高。
