Oncology Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Cancer. 2023 Sep 15;129(18):2789-2797. doi: 10.1002/cncr.34918. Epub 2023 Jun 24.
Diabetes mellitus (DM) is a highly prevalent chronic metabolic disorder. Although DM has been associated with immune dysfunction, the effect of DM on the efficacy of immunotherapy is unknown. This study aimed to evaluate the impact of DM on the efficacy of pembrolizumab in metastatic non-small cell lung cancer (NSCLC).
The authors reviewed the medical records of consecutive metastatic NSCLC patients treated with first-line pembrolizumab either alone or in combination with chemotherapy at a single tertiary center. For validation, a computerized data from Maccabi Healthcare Services, a 2.5-million-member state health service was used.
Of the 203 eligible patients, 51 (25%) had DM. Patients with DM had a significantly shorter median progression-free survival (PFS) (5.9 vs. 7.1 months, p = .004) and overall survival (OS) (12 vs. 21 months, p = .006). The shorter OS in diabetic patients was more pronounced when pembrolizumab was given alone (12 vs. 27 months, p = .03) than when combined with chemotherapy (14.3 vs. 19.4 months, p = .06). Multivariate analysis confirmed DM as an independent risk factor for shorter PFS (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.11-2.50, p = .01) and OS (HR, 1.73; 95% CI, 1.09-2.76, p = .02). In a validation cohort of 452 metastatic NSCLC patients, the time on pembrolizumab treatment was shorter in diabetic patients (p = .025), with only 19.6% of patients remaining on treatment at 12 months compared to 31.7% of the nondiabetic patients.
This study suggests immunotherapy is less beneficial in diabetic NSCLC patients. More work is needed to verify our findings and explore similar effects in other cancer entities.
糖尿病（DM）是一种高发的慢性代谢紊乱疾病。虽然 DM 与免疫功能障碍有关，但 DM 对免疫疗法疗效的影响尚不清楚。本研究旨在评估 DM 对转移性非小细胞肺癌（NSCLC）患者一线帕博利珠单抗单药或联合化疗疗效的影响。
作者回顾了在一家三级中心接受一线帕博利珠单抗单药或联合化疗治疗的连续转移性 NSCLC 患者的病历。为了验证，还使用了 Maccabi 医疗保健服务的计算机化数据，该服务是一个拥有 250 万成员的国家卫生服务机构。
在 203 名符合条件的患者中，有 51 名（25%）患有 DM。患有 DM 的患者中位无进展生存期（PFS）（5.9 个月 vs. 7.1 个月，p =.004）和总生存期（OS）（12 个月 vs. 21 个月，p =.006）明显更短。当帕博利珠单抗单药治疗时，糖尿病患者的 OS 更短（12 个月 vs. 27 个月，p =.03），而与化疗联合治疗时则更短（14.3 个月 vs. 19.4 个月，p =.06）。多变量分析证实 DM 是较短 PFS（风险比[HR]，1.67；95%置信区间[CI]，1.11-2.50，p =.01）和 OS（HR，1.73；95% CI，1.09-2.76，p =.02）的独立危险因素。在 452 名转移性 NSCLC 患者的验证队列中，糖尿病患者接受帕博利珠单抗治疗的时间更短（p =.025），12 个月时仅有 19.6%的患者仍在接受治疗，而无糖尿病患者为 31.7%。
本研究表明免疫疗法对糖尿病 NSCLC 患者的益处较小。需要进一步的工作来验证我们的发现，并探讨在其他癌症实体中类似的影响。
