Simultaneous Durvalumab and Platinum-Based Chemoradiotherapy in Unresectable Stage III Non-Small Cell Lung Cancer: The Phase III PACIFIC-2 Study.

Earlier administration of immunotherapy, simultaneously with cCRT, may improve outcomes further.

更早地与cCRT同时进行免疫治疗可能会进一步改善预后。

Methods

Eligible patients were randomly assigned (2:1) to receive either durvalumab or placebo administered from the start of cCRT.

符合条件的患者按2:1的比例随机分配接受durvalumab或安慰剂治疗，从cCRT开始时给药。

Patients without progression after completing cCRT received consolidation durvalumab or placebo (per initial random assignment) until progression.

在完成cCRT后没有进展的患者继续接受巩固治疗，使用durvalumab或安慰剂（根据最初的随机分配），直至疾病进展。

The primary end point was progression-free survival(PFS) by blinded independent central review.

主要终点是通过双盲独立中央审查的无进展生存期（PFS）

Key secondary end points included objective response rate(ORR), overall survival(OS), the proportion of patients alive at 24 months (OS24), and safety.

关键次要终点包括客观缓解率（ORR）、总生存期（OS）、24个月时存活的患者比例（OS24）以及安全性。

Results

In total, 328 patients were randomly assigned to receive durvalumab (n = 219) or placebo (n = 109).

共有328名患者被随机分配接受durvalumab治疗（n = 219）或安慰剂（n = 109）。

There was no statistically significant difference with durvalumab versus placebo in PFS (hazard ratio[HR], 0.85 [95% CI, 0.65 to 1.12]; P = .247) or OS (HR, 1.03 [95% CI, 0.78 to 1.39]; P = .823); OS24 was 58.4% versus 59.5%, respectively.

在无进展生存期（PFS）和总生存（OS）方面，durvalumab与安慰剂相比没有统计学显著差异（PFS的危险比[HR]为0.85 [95%置信区间，0.65至1.12]；P = .247；OS的HR为1.03 [95%置信区间，0.78至1.39]；P = .823）；24个月的总生存率分别为58.4%和59.5%。

Confirmed ORR was 60.7% with durvalumab versus 60.6% with placebo (difference, 0.2% [95% CI, -15.2 to 16.3%]; P = .976).

确认的客观缓解率(ORR)为60.7%使用durvalumab治疗，与使用安慰剂的60.6%相比（差异，0.2% [95% 置信区间, -15.2 到 16.3%]；P = .976）。

With durvalumab versus placebo, respectively, maximum grade 3 or 4 adverse events (AEs) occurred in 53.4% versus 59.3% of patients, pneumonitis or radiation pneumonitis (group term) in 28.8% (grade ≥3: 4.6%) versus 28.7% (grade ≥3: 5.6%), AEs leading to discontinuation of durvalumab or placebo in 25.6% versus 12.0%, and fatal AEs in 13.7% versus 10.2%.

使用durvalumab与安慰剂相比，分别有53.4%和59.3%的患者出现了最大级别的3级或4级不良事件(AEs)，其中肺炎或放射性肺炎（组术语）的发生率为28.8%（3级或以上：4.6%）与28.7%（3级或以上：5.6%），导致durvalumab或安慰剂停药的不良事件发生率为25.6%与12.0%，致命不良事件的发生率为13.7%与10.2%。

Conclusions

Among patients with unresectable stage III NSCLC, durvalumab administered from the start of cCRT failed to demonstrate additional benefit compared with cCRT plus placebo.

在不可切除的III期非小细胞肺癌患者中，从cCRT开始时给予的durvalumab与cCRT加安慰剂相比，未能显示出额外的益处。

Consolidation durvalumab following definitive cCRT remains the standard of care in this setting.

在这一背景下，巩固性durvalumab治疗在完成根治性cCRT后仍然是标准治疗。