Department of Internal Medicine, UC Davis Comprehensive Cancer Center, Sacramento, California, USA
Lungen Clinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.
J Immunother Cancer. 2021 Mar;9(3). doi: 10.1136/jitc-2020-001882.
Treatment-induced accelerated tumor growth is a progression pattern reported with immune checkpoint inhibitors that has never been evaluated in randomized phase III studies because it requires two pretreatment scans. This study aimed to develop clinically relevant and applicable criteria for fast progression (FP), incorporating tumor growth kinetics and early death from disease progression to analyze data from the randomized phase III OAK study.
The OAK study evaluated the efficacy and safety of atezolizumab versus docetaxel as second-line or third-line treatment for stage IIIb/IV non-small cell lung cancer. FP rates and associated baseline factors were analyzed. FP was defined as either a ≥50% increase in the sum of largest diameters (SLDs) within 6 weeks of treatment initiation or death due to cancer progression within 12 weeks (absent post-baseline scan).
Forty-two of 421 patients (10%) receiving atezolizumab and 37 of 402 (9%) receiving docetaxel had FP. Twenty patients with FP (48%) receiving atezolizumab versus 12 (30%) receiving docetaxel had a ≥50% SLD increase within 6 weeks. FP was significantly associated with an ECOG (Eastern Cooperative Oncology Group) performance status of 1 (vs 0), ≥3 metastatic sites at baseline, and failure of preceding first-line treatment within 6 months, but not with epidermal growth factor receptor mutation, programmed cell death 1 ligand 1 or tumor mutational burden. Overall survival in patients with FP and a ≥50% SLD increase at week 6 was similar with atezolizumab and docetaxel (unstratified HR 0.89 (95% CI 0.41 to 1.92)).
FP rates were similar with atezolizumab and docetaxel in the OAK study, suggesting that FP may not be unique to checkpoint inhibitors, although the underlying mechanisms may differ from those of chemotherapy. Applying the FP criteria to other phase III checkpoint inhibitor trials may further elucidate the risk factors for FP.
NCT02008227.
治疗诱导的肿瘤加速生长是一种与免疫检查点抑制剂相关的进展模式，由于需要两次预处理扫描，因此从未在随机 III 期研究中进行评估。本研究旨在制定临床相关和适用的快速进展（FP）标准，纳入肿瘤生长动力学和疾病进展导致的早期死亡，以分析来自随机 III 期 OAK 研究的数据。
OAK 研究评估了阿特珠单抗对比多西他赛作为 IIIB/IV 期非小细胞肺癌二线或三线治疗的疗效和安全性。分析了 FP 发生率和相关的基线因素。FP 定义为治疗开始后 6 周内 SLD 总和增加≥50%或 12 周内因癌症进展而死亡（无基线后扫描）。
接受阿特珠单抗治疗的 421 例患者中有 42 例（10%）和接受多西他赛治疗的 402 例患者中有 37 例（9%）发生 FP。20 例 FP 患者（48%）接受阿特珠单抗治疗，12 例（30%）接受多西他赛治疗，在 6 周内 SLD 增加≥50%。FP 与 ECOG（东部肿瘤协作组）表现状态为 1（vs 0）、基线时≥3 个转移部位和 6 个月内一线治疗失败显著相关，但与表皮生长因子受体突变、程序性死亡配体 1 或肿瘤突变负荷无关。在 6 周时 SLD 增加≥50%的 FP 患者中，阿特珠单抗和多西他赛的总生存期相似（无分层 HR 0.89（95%CI 0.41 至 1.92））。
在 OAK 研究中，阿特珠单抗和多西他赛的 FP 发生率相似，这表明 FP 可能不是检查点抑制剂所特有的，尽管潜在的机制可能与化疗不同。将 FP 标准应用于其他 III 期检查点抑制剂试验可能会进一步阐明 FP 的危险因素。
NCT02008227。
