Department of Medicine (Hematology/Oncology), University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria, Australia.
J Natl Cancer Inst. 2021 Nov 29;113(12):1733-1743. doi: 10.1093/jnci/djab108.
In the phase III IMpassion130 study, atezolizumab plus nab-paclitaxel (A+nP) showed clinical benefit in advanced or metastatic triple-negative breast cancer patients who were programmed death-ligand 1 (PD-L1)+ (tumor-infiltrating immune cells [IC] ≥1%) using the SP142 immunohistochemistry assay. Here we evaluate 2 other PD-L1 assays for analytical concordance with SP142 and patient-associated clinical outcomes.
Samples from 614 patients (68.1% of intention-to-treat population) were centrally evaluated by immunohistochemistry for PD-L1 status on IC (VENTANA SP142, SP263, Dako 22C3) or as a combined positive score (CPS; 22C3).
Using SP142, SP263, and 22C3 assays, PD-L1 IC ≥1% prevalence was 46.4% (95% confidence interval [CI] = 42.5% to 50.4%), 74.9% (95% CI = 71.5% to 78.3%), and 73.1% (95% CI = 69.6% to 76.6%), respectively; 80.9% were 22C3 CPS ≥1. At IC ≥1% (+), the analytical concordance between SP142 and SP263 and 22C3 was 69.2% and 68.7%, respectively. Almost all SP142+ cases were captured by other assays (double positive), but several SP263+ (29.6%) or 22C3+ (29.0%) cases were SP142- (single positive). A+nP clinical activity vs placebo+nP in SP263+ and 22C3+ patients (progression-free survival [PFS] hazard ratios [HRs] = 0.64 to 0.68; overall survival [OS] HRs = 0.75 to 0.79) was driven by double-positive cases (PFS HRs = 0.60 to 0.61; OS HRs = 0.71 to 0.75) rather than single-positive cases (PFS HRs = 0.68 to 0.81; OS HRs = 0.87 to 0.95). Concordance for harmonized cutoffs for SP263 (IC ≥4%) and 22C3 (CPS ≥10) to SP142 (IC ≥1%) was subpar (approximately 75%).
22C3 and SP263 assays identified more patients as PD-L1+ (IC ≥1%) than SP142. No inter-assay analytical equivalency was observed. Consistent improved A+nP efficacy was captured by the SP142 PD-L1 IC ≥1% subgroup nested within 22C3 and SP263 PD-L1+ (IC ≥1%) populations.
在 III 期 IMpassion130 研究中，阿替利珠单抗联合 nab-紫杉醇（A+nP）在程序性死亡配体 1（PD-L1）阳性（肿瘤浸润免疫细胞 [IC]≥1%，采用 SP142 免疫组化检测）的晚期或转移性三阴性乳腺癌患者中显示出临床获益。在此，我们评估了另外 2 种 PD-L1 检测方法与 SP142 的分析一致性以及与患者相关的临床结局。
614 例患者（意向治疗人群的 68.1%）的样本采用免疫组化法，使用 VENTANA SP142、SP263、Dako 22C3 检测 PD-L1 在 IC 上的状态（PD-L1 IC）或作为联合阳性评分（CPS；22C3）进行中心评估。
采用 SP142、SP263 和 22C3 检测，PD-L1 IC≥1%的患病率分别为 46.4%（95%置信区间 [CI] = 42.5%至 50.4%）、74.9%（95% CI = 71.5%至 78.3%）和 73.1%（95% CI = 69.6%至 76.6%）；80.9%为 22C3 CPS≥1。在 PD-L1 IC≥1%（+）时，SP142 与 SP263 和 22C3 的分析一致性分别为 69.2%和 68.7%。几乎所有 SP142+病例都被其他检测方法（双阳性）捕获，但有一些 SP263+（29.6%）或 22C3+（29.0%）病例为 SP142-（单阳性）。SP263+和 22C3+患者中 A+nP 的临床活性（无进展生存期 [PFS]风险比 [HR] = 0.64 至 0.68；总生存期 [OS] HR = 0.75 至 0.79）与安慰剂+nP 相比，主要是由双阳性病例（PFS HR = 0.60 至 0.61；OS HR = 0.71 至 0.75）驱动，而不是单阳性病例（PFS HR = 0.68 至 0.81；OS HR = 0.87 至 0.95）。SP263（IC≥4%）和 22C3（CPS≥10）与 SP142（IC≥1%）的协调截断值的一致性欠佳（约 75%）。
22C3 和 SP263 检测方法比 SP142 检测方法识别出更多的 PD-L1+（IC≥1%）患者。未观察到各检测方法之间的分析等效性。在 SP142 PD-L1 IC≥1%亚组内嵌套的 22C3 和 SP263 PD-L1+（IC≥1%）人群中，观察到 A+nP 疗效一致改善。
