The Fourth Affiliated Hospital of China Medical University, Chongshan East Road #4, Huanggu District, Liaoning, 110032, China.
BMC Cancer. 2023 Oct 10;23(1):962. doi: 10.1186/s12885-023-11472-3.
The PACIFIC study has demonstrated that the administration of durvalumab following concurrent chemoradiotherapy can significantly improve both overall survival and progression-free survival rates in patients with locally advanced unresectable non-small cell lung cancer. While the latest NCCN guidelines recommend this combination regimen, they do not specify the optimal timing for administering durvalumab after completing radiotherapy. The PACIFIC study suggested initiating durvalumab within 42 days of completing radiotherapy, but early administration of the drug may increase the incidence of pneumonitis. Therefore, we conducted this study to investigate whether the time interval between completion of radiotherapy and initiation of durvalumab treatment is associated with the risk of pneumonitis (Grade ≥ 3), which is the primary endpoint, as well as progression-free survival, which is the secondary endpoint.
A comprehensive search of clinical trials in PubMed and EMBASE was conducted up to March 2023 to identify clinical trials involving locally advanced unresectable non-small cell lung cancer patients who were treated with durvalumab following chemoradiotherapy. Meta-analysis was performed on single-arm studies to estimate the incidence of pneumonitis (Grade ≥ 3) and progression-free survival in all studies, as well as in studies that administered durvalumab within 42 days after completion of radiotherapy.
This meta-analysis consisted of nine studies with a total of 2560 patients. The analysis showed that the incidence of pneumonitis (Grade ≥ 3) was 5.36% [95%CI (0.03, 0.08), I = 18.41%, p = 0.29], while the 1-year progression-free survival rate was 57.91% [95%CI (0.53, 0.63), I = 10.57%, p = 0.35]. Furthermore, when the duration between completion of radiotherapy and initiation of durvalumab treatment was shorter than 42 days, the incidence of pneumonitis (Grade ≥ 3) was 4.12% [95%CI (0.02, 0.06), I = 0.00%, p = 0.56], with a 1-year progression-free survival rate of 61.03% [95%CI (0.51, 0.71), I = 59.06%, p = 0.09].
Overall, based on the available evidence, it appears that there is no significant increase in pneumonitis or decrease in progression-free survival (PFS) when the time interval is less than 42 days and a shorter interval between treatment sessions does not necessarily have a detrimental effect on the rate of pneumonitis. We recommend that clinicians carefully evaluate the specific circumstances of each patient to determine the optimal timing for initiating immunotherapy.
PACIFIC 研究表明，在局部晚期不可切除的非小细胞肺癌患者中，同步放化疗后使用 durvalumab 可显著提高总生存率和无进展生存率。尽管最新的 NCCN 指南推荐了这种联合治疗方案，但并未指定在完成放疗后使用 durvalumab 的最佳时机。PACIFIC 研究建议在完成放疗后 42 天内开始使用 durvalumab，但该药的早期给药可能会增加肺炎的发生率。因此，我们进行了这项研究，以调查放疗完成后开始 durvalumab 治疗的时间间隔是否与肺炎（≥3 级）风险（主要终点）以及无进展生存率（次要终点）相关。
对PubMed 和 EMBASE 中的临床试验进行全面检索，截至 2023 年 3 月，以确定接受放化疗后接受 durvalumab 治疗的局部晚期不可切除非小细胞肺癌患者的临床试验。对单臂研究进行荟萃分析，以估计所有研究以及在放疗完成后 42 天内使用 durvalumab 的研究中肺炎（≥3 级）和无进展生存率的发生率。
这项荟萃分析包括 9 项研究，共有 2560 名患者。分析表明，肺炎（≥3 级）的发生率为 5.36%[95%CI（0.03，0.08），I=18.41%，p=0.29]，而 1 年无进展生存率为 57.91%[95%CI（0.53，0.63），I=10.57%，p=0.35]。此外，当放疗完成与 durvalumab 治疗开始之间的时间间隔短于 42 天时，肺炎（≥3 级）的发生率为 4.12%[95%CI（0.02，0.06），I=0.00%，p=0.56]，1 年无进展生存率为 61.03%[95%CI（0.51，0.71），I=59.06%，p=0.09]。
总的来说，根据现有证据，当时间间隔小于 42 天时，肺炎发生率或无进展生存率（PFS）并没有显著增加，较短的治疗间隔不一定会对肺炎发生率产生不利影响。我们建议临床医生仔细评估每位患者的具体情况，以确定开始免疫治疗的最佳时机。
