Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Vanderbilt University, Nashville, TN.
J Clin Oncol. 2021 Jul 10;39(20):2247-2256. doi: 10.1200/JCO.21.00280. Epub 2021 May 17.
Predictive biomarkers to identify patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who may benefit from targeted therapy alone are required. We hypothesized that early measurements of tumor maximum standardized uptake value corrected for lean body mass (SULmax) on F-labeled fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) would predict pathologic complete response (pCR) to pertuzumab and trastuzumab (PT).
Patients with stage II or III, estrogen receptor-negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. F-labeled fluorodeoxyglucose positron emission tomography-computed tomography was performed at baseline and 15 days after PT initiation (C1D15). Eighty evaluable patients were required to test the null hypothesis that the area under the curve of percent change in SULmax by C1D15 predicting pCR is ≤ 0.65, with a one-sided type I error rate of 10%.
Eighty-eight women were enrolled (83 evaluable), and 85% (75 of 88) completed all four cycles of PT. pCR after PT alone was 22%. Receiver operator characteristic analysis of percent change in SULmax by C1D15 yielded an area under the curve of 0.72 (80% CI, 0.64 to 0.80; one-sided = .12), which did not reject the null hypothesis. However, between patients who obtained pCR and who did not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8% 41.8%; = .004) and SULmax reduction ≥ 40% was more prevalent (83% 52%; = .03; positive predictive value, 31%). Participants not obtaining a 40% reduction in SULmax by C1D15 were unlikely to obtain pCR (negative predictive value, 91%).
Although the primary objective was not met, early changes in SULmax predict response to PT in estrogen receptor-negative and HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate tailoring of therapy in this setting.
需要预测生物标志物，以确定人表皮生长因子受体 2（HER2）阳性乳腺癌患者是否可能从单独的靶向治疗中获益。我们假设，通过 F 标记的氟脱氧葡萄糖正电子发射断层扫描-计算机断层扫描（PET-CT）对瘦体重校正的肿瘤最大标准化摄取值（SULmax）的早期测量将预测曲妥珠单抗和帕妥珠单抗（PT）治疗的病理完全缓解（pCR）。
Ⅱ期或Ⅲ期、雌激素受体阴性、HER2 阳性乳腺癌患者接受了四个周期的新辅助 PT 治疗。在 PT 开始后第 15 天（C1D15）进行 F 标记的氟脱氧葡萄糖正电子发射断层扫描-计算机断层扫描。需要 80 例可评估患者来检验以下零假设，即 C1D15 时 SULmax 变化百分比曲线下面积预测 pCR 的结果是否≤0.65，单侧Ⅰ型错误率为 10%。
共入组 88 例女性（83 例可评估），85%（75/88）完成了所有四个周期的 PT 治疗。PT 单独治疗后的 pCR 为 22%。C1D15 时 SULmax 变化百分比的受试者工作特征分析得到的曲线下面积为 0.72（80%CI，0.64 至 0.80；单侧 =.12），未拒绝零假设。然而，在获得 pCR 的患者和未获得 pCR 的患者之间，C1D15 时 SULmax 中位数的降低率存在显著差异（63.8% 41.8%； =.004），并且 SULmax 降低≥40%更为常见（83% 52%； =.03；阳性预测值，31%）。在 C1D15 时未获得 SULmax 降低 40%的患者不太可能获得 pCR（阴性预测值，91%）。
尽管主要目标没有达到，但 SULmax 的早期变化可预测雌激素受体阴性和 HER2 阳性乳腺癌对 PT 的反应。一旦得到优化，这种定量成像策略可能有助于在这种情况下调整治疗。
