Edwards Donna M, Sankar Kamya, Alseri Aaren, Jiang Ralph, Schipper Matthew, Miller Sean, Dess Kathryn, Strohbehn Garth W, Elliott David A, Moghanaki Drew, Ramnath Nithya, Green Michael D, Bryant Alex K
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan.
Department of Medicine, Division of Medical Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Int J Radiat Oncol Biol Phys. 2024 Mar 15;118(4):963-970. doi: 10.1016/j.ijrobp.2023.09.050. Epub 2023 Oct 2.
Adjuvant durvalumab after definitive chemoradiotherapy (CRT) for unresectable stage III non-small cell lung cancer (NSCLC) is well-tolerated in clinical trials. However, pneumonitis rates outside of clinical trials remain poorly defined with CRT followed by durvalumab. We aimed to describe the influence of durvalumab on pneumonitis rates among a large cohort of patients with stage III NSCLC.
We studied patients with stage III NSCLC in the national Veterans Health Administration from 2015 to 2021 who received concurrent CRT alone or with adjuvant durvalumab. We defined pneumonitis as worsening respiratory symptoms with radiographic changes within 2 years of CRT and graded events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. We used Cox regression to analyze risk factors for pneumonitis and the effect of postbaseline pneumonitis on overall survival.
Among 1994 patients (989 CRT alone, 1005 CRT followed by adjuvant durvalumab), the 2-year incidence of grade 2 or higher pneumonitis was 13.9% for CRT alone versus 22.1% for CRT plus durvalumab (unadjusted P < .001). On multivariable analysis, durvalumab was associated with higher risk of grade 2 pneumonitis (hazard ratio, 1.45; 95% CI, 1.09-1.93; P = .012) but not grade 3 to 5 pneumonitis (P = .2). Grade 3 pneumonitis conferred worse overall survival (hazard ratio, 2.51; 95% CI, 2.06-3.05; P < .001) but grade 2 pneumonitis did not (P = .4).
Adjuvant durvalumab use was associated with increased risk of low-grade but not higher-grade pneumonitis. Reassuringly, low-grade pneumonitis did not increase mortality risk. We observed increased rates of high-grade pneumonitis relative to clinical trials; the reasons for this require further study.
在不可切除的III期非小细胞肺癌（NSCLC）的确定性放化疗（CRT）后使用辅助性度伐利尤单抗，在临床试验中耐受性良好。然而，在临床试验之外，CRT联合度伐利尤单抗后的肺炎发生率仍未明确界定。我们旨在描述度伐利尤单抗对一大群III期NSCLC患者肺炎发生率的影响。
我们研究了2015年至2021年期间在美国退伍军人健康管理局接受单独同步CRT或联合辅助性度伐利尤单抗治疗的III期NSCLC患者。我们将肺炎定义为CRT后2年内出现影像学改变且呼吸道症状恶化，并根据美国国立癌症研究所不良事件通用术语标准第4.03版对事件进行分级。我们使用Cox回归分析肺炎的危险因素以及基线后肺炎对总生存期的影响。
在1994例患者中（989例单独接受CRT，1005例CRT后接受辅助性度伐利尤单抗），单独CRT组2级或更高级别肺炎的2年发生率为13.9%，而CRT加度伐利尤单抗组为22.1%（未校正P <.001）。多变量分析显示，度伐利尤单抗与2级肺炎的较高风险相关（风险比，1.45；95%CI，1.09 - 1.93；P =.012），但与3至5级肺炎无关（P =.2）。3级肺炎导致总体生存期更差（风险比，2.51；95%CI，2.06 - 3.05；P <.001），但2级肺炎并非如此（P =.4）。
辅助使用度伐利尤单抗与低级别而非高级别肺炎的风险增加相关。令人放心的是，低级别肺炎并未增加死亡风险。我们观察到相对于临床试验，高级别肺炎的发生率有所增加；其原因需要进一步研究。
