Patterns of Disease Progression with Durvalumab in Stage III Non-small Cell Lung Cancer (PACIFIC)
D. Raben
Purpose/Objective(s): In the ph 3 PACIFIC study of unresectable, Stage III NSCLC pts without progression after chemoradiotherapy (CRT), durvalumab (durva) demonstrated significant improvements versus placebo (pbo) in the primary endpoints progression-free survival and overall survival, with manageable safety and no detrimental effect on pt-reported outcomes. We performed exploratory analyses to characterize patterns of disease progression, including the sites of first progression.
Materials/Methods: Pts with WHO PS 0/1 (any tumor PD-L1 status) who received 2 cycles of platinum-based CRT were randomized (2:1), 1e42 days following CRT, to receive durva or pbo up to 12 months, stratified by age, sex, and smoking history. Disease progression was assessed by blinded independent central review (RECIST v1.1). Scans were re-evaluated for unequivocal new lesions by a new, independent reviewer. New lesions identified within the chest wall, including the diaphragm, were categorized as intra-thoracic (local), with all other lesions categorized as extra-thoracic (distant). The proportions of pts with progression (or death), region of first progression, location and number of organs with new lesions, and number of new lesions at progression were descriptively summarized. Time to progression by region was estimated by Kaplan-Meier method with between- treatment HRs calculated by stratified Log rank test.
Results: 713 ptswere randomized (durva, nZ476; pbo, nZ237). As ofMarch 22, 2018, 45.4% and 64.6% in the durva and pbo groups, respectively, had disease progression or death.Local only (intra-thoracic) progression occurred in 36.6% and 48.1%, respectively; distant only (extra-thoracic) progression in 6.9% and 13.1%; and simultaneous local and distant progression in 1.9% and 3.4%. New extra-thoracic lesions at first progression occurred in 8.8% and 16.5% in the durva and pbo groups, respectively. Most new distant lesions occurred in a single organ (8.4% and 15.6%of all patients). The most common site at progression was the brain, among 61.9% and 66.7% of pts with extrathoracic lesions, of whom pts in the durva and pbo groups presented with 1 (46.2% and 34.6%), 2 (30.8% and 34.6%), 3e5 (23.1% and 19.2%), or > 5 brain lesions (0 and 11.5%). Median time to first progression in each regionwas improvedwith durva versus pbo (local only: 25.2 vs. 9.2 months [HR, 0.55;95% CI, 0.43e0.70]; distant only: not reached [NR] vs. NR [HR, 0.41; 95% CI, 0.27e0.63]; and both: NR vs. NR [HR, 0.48; 95% CI, 0.28e0.82]).
Conclusion: Most pts experienced their first progression inside the thorax regardless of treatment arm; however, fewer pts receiving durva experienced local and/or distant progression. In addition, the time to first progression was improved with durva versus pbo regardless of location. Most new distant lesions were detected in a single organ, with>90% of pts having5 lesions, which suggests that local ablative therapy may extend survival.
LA-NSCLC 同步化放疗
Durvalumab 巩固治疗可改善PFS 但放射性肺炎发生较高
韩国成均馆大学医学院Jung
等报告，在局部晚期非小细胞肺
癌（LA-NSCLC）患者临床实践
中，同步化放疗后Durvalumab 巩
固治疗有助于改善无进展生存期
（PFS）；但因其相关的放射性肺
炎发生率较高，需要仔细遴选患
者及监测和管理。（Lung Cancer.
2020 年5 月31 日在线版 doi:
10.1016/j.lungcan.2020.05.035）
PACIFIC 研究表明，在无法切
除的局部晚期非小细胞肺癌（LANSCLC）
患者中，Durvalumab 巩
固治疗对PFS 和总生存期（OS）
均有益。但在实际操作中，无法
切除的LA-NSCLC 患者的异质性
不同，肿瘤负荷和临床因素也不
同。因此，明确Durvalumab 在临
床实践中的疗效和不良事件非常
重要。该项单机构研究纳入了不
可切除的LA-NSCLC 患者，给予
同步化放疗（CCRT）， 调查了
Durvalumab 巩固治疗的疗效和放
射性肺炎的发生率。
结果显示，总体而言，55.3%
的患者不符合PACIFIC 研究标
准， 但仍在实际操作中接受了
Durvalumab 巩固治疗。在所有人
群以及不符合PACIFIC 研究标
准的患者亚组中，Durvalumab 巩
固治疗与良好的PFS 相关。但Durvalumab 组中放射性肺炎的发生率更高， 尤其是在CCRT 后3~6 个月内。Durvalumab 组的3 级放射性肺炎发生率为14.3%，而观察组为2.5%。
