Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oncologist. 2021 May;26(5):433-438. doi: 10.1002/onco.13752. Epub 2021 Mar 25.
The U.S. Food and Drug Administration (FDA) granted approval to atezolizumab and durvalumab in March of 2019 and 2020, respectively, for use in combination with chemotherapy for first-line treatment of patients with extensive stage small cell lung cancer. These approvals were based on data from two randomized controlled trials, IMpower133 (atezolizumab) and CASPIAN (durvalumab). Both trials demonstrated an improvement in overall survival (OS) with anti-programmed death ligand 1 antibodies when added to platinum-based chemotherapy as compared with chemotherapy alone. In IMpower133, patients receiving atezolizumab with etoposide and carboplatin demonstrated improved OS (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.54-0.91; p = .0069), with median OS of 12.3 months compared with 10.3 months in patients receiving etoposide and carboplatin. In CASPIAN, patients receiving durvalumab with etoposide and either cisplatin or carboplatin also demonstrated improved OS (HR, 0.73; 95% CI, 0.59-0.91; p = .0047) with median OS of 13.0 months compared with 10.3 months in patients receiving etoposide and either cisplatin or carboplatin. The safety profiles of both drugs were generally consistent with known toxicities of immune-checkpoint inhibitor therapies. This review summarizes the FDA perspective and data supporting the approval of these two agents. IMPLICATIONS FOR PRACTICE: Effective therapeutic options for small cell lung cancer (SCLC) are limited, and there has been modest improvement in the overall survival (OS) of patients with SCLC over the past 3 decades. The approvals of atezolizumab and of durvalumab in combination with chemotherapy for first-line treatment of patients with extensive stage SCLC represent the first approved therapies with OS benefit for this patient population since the approval of etoposide in combination with other approved chemotherapeutic agents. Additionally, the efficacy results from IMpower133 and CASPIAN lay the groundwork for possible further evaluation in other treatment settings in this disease.
美国食品和药物管理局（FDA）分别于 2019 年 3 月和 2020 年批准阿替利珠单抗和度伐利尤单抗与化疗联合用于广泛期小细胞肺癌（SCLC）的一线治疗。这些批准基于两项随机对照试验（IMpower133[阿替利珠单抗]和 CASPIAN[度伐利尤单抗]）的数据。这两项试验均表明，与单独化疗相比，抗程序性死亡配体 1 抗体联合铂类化疗可改善总生存期（OS）。在 IMpower133 中，接受阿替利珠单抗联合依托泊苷和顺铂或卡铂治疗的患者 OS 得到改善（风险比[HR]，0.70；95%置信区间[CI]，0.54-0.91；p=0.0069），中位 OS 为 12.3 个月，而接受依托泊苷和顺铂或卡铂治疗的患者中位 OS 为 10.3 个月。在 CASPIAN 中，接受度伐利尤单抗联合依托泊苷和顺铂或卡铂治疗的患者 OS 也得到改善（HR，0.73；95%CI，0.59-0.91；p=0.0047），中位 OS 为 13.0 个月，而接受依托泊苷和顺铂或卡铂治疗的患者中位 OS 为 10.3 个月。这两种药物的安全性概况通常与免疫检查点抑制剂治疗的已知毒性一致。本综述总结了 FDA 的观点和支持这两种药物批准的数据。
小细胞肺癌（SCLC）的有效治疗选择有限，在过去 30 年中，SCLC 患者的总体生存（OS）仅略有改善。阿替利珠单抗和度伐利尤单抗联合化疗用于广泛期 SCLC 患者的一线治疗获得批准，这是自依托泊苷联合其他已批准化疗药物获得批准以来，该患者群体中首次获得 OS 获益的批准疗法。此外，IMpower133 和 CASPIAN 的疗效结果为该疾病其他治疗环境的进一步评估奠定了基础。
