Introduction: Osimertinib is a third‐generation EGFR‐tyrosine kinase inhibitor (TKI). Durvalumab is an anti–programmed death ligand 1 monoclonal antibody. The phase III open‐label CAURAL trial (NCT02454933) investigated osimertinib plus durvalumab versus osimertinib monotherapy in patients with EGFR‐TKI sensitizing and EGFR T790M mutation–positive advanced NSCLC and disease progression after EGFR‐TKI therapy. Methods: Patients were randomly assigned 1:1 to receive orally administered osimertinib (80 mg once daily) with or without durvalumab (10 mg/kg administered intravenously every 2 weeks) until progression. Treatment could continue beyond progression, providing clinical benefit continued (judged by the investigator). The amended primary objective was to assess the safety and tolerability of osimertinib plus durvalumab; efficacy was an exploratory objective. Results: CAURAL recruitment was terminated early because of increased incidence of interstitial lung disease–like events in the osimertinib plus durvalumab arm from the separate phase Ib TATTON trial (NCT02143466). At termination of CAURAL recruitment, 15 patients had been randomly assigned to treatment with osimertinib and 14 to treatment with osimertinib plus durvalumab. The most common AEs were diarrhea (53% [grade ≥3 in 6% of patients]) in the osimertinib arm and rash (67% [grade ≥3 in 0 patients]) in the combination arm. One patient who had been randomized to the combination arm reported grade 2 interstitial lung disease while receiving osimertinib monotherapy (after discontinuing durvalumab therapy after one dose). The objective response rates were 80% in the osimertinib arm and 64% in the combination arm. Conclusion: Limited patient numbers preclude formal safety and efficacy comparisons between the two treatment arms. The combination of programmed cell death 1/programmed death ligand 1 inhibitors and EGFR‐TKIs as therapy for NSCLC is not well understood, but it requires a careful approach if considered in the future.

中文翻译：

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奥希替尼加度伐单抗对比奥希替尼单药治疗既往 EGFR-TKI 治疗后的 EGFR T790M 阳性 NSCLC：CAURAL 简要报告

简介：奥希替尼是第三代EGFR-酪氨酸激酶抑制剂（TKI）。Durvalumab 是一种抗程序性死亡配体 1 单克隆抗体。III 期开放标签 CAURAL 试验 (NCT02454933) 在 EGFR-TKI 致敏和 EGFR T790M 突变阳性晚期 NSCLC 和 EGFR-TKI 治疗后疾病进展的患者中研究了奥希替尼加 durvalumab 与奥希替尼单药治疗。方法：患者按 1:1 随机分配接受口服奥希替尼（80 mg，每天一次），联合或不联合 durvalumab（每 2 周静脉注射 10 mg/kg）直至疾病进展。治疗可以在进展后继续，提供持续的临床益处（由研究者判断）。修订后的主要目标是评估奥希替尼加 durvalumab 的安全性和耐受性；疗效是一个探索性目标。结果：由于来自单独的 Ib 期 TATTON 试验 (NCT02143466) 的 osimertinib 加 durvalumab 组中间质性肺病样事件的发生率增加，CAURAL 招募提前终止。在 CAURAL 招募结束时，15 名患者被随机分配接受奥希替尼治疗，14 名患者接受奥希替尼加 durvalumab 治疗。最常见的 AE 是奥希替尼组的腹泻（53% [6% 的患者≥3 级]）和联合组的皮疹（67% [0 名患者的≥3 级]）。一名随机分配到联合治疗组的患者在接受奥希替尼单药治疗时报告了 2 级间质性肺病（在一剂后停止 durvalumab 治疗后）。奥希替尼组的客观缓解率为 80%，联合组为 64%。结论：有限的患者数量妨碍了两个治疗组之间正式的安全性和有效性比较。程序性细胞死亡 1/程序性死亡配体 1 抑制剂和 EGFR-TKI 联合治疗非小细胞肺癌尚不清楚，但如果将来考虑，需要谨慎处理。