Manchester University NHS Foundation Trust and University of Manchester, Manchester, United Kingdom.
The Institute of Cancer Research, Clinical Trials and Statistics Unit, London, United Kingdom.
Clin Cancer Res. 2022 Apr 1;28(7):1323-1334. doi: 10.1158/1078-0432.CCR-21-3177.
EPHOS-B aimed to determine whether perioperative anti-HER2 therapy inhibited proliferation and/or increased apoptosis in HER2-positive breast cancer.
This randomized phase II, two-part, multicenter trial included newly diagnosed women with HER2-positive invasive breast cancer due to undergo surgery. Patients were randomized to: part 1 (1:2:2), no treatment (control), trastuzumab or lapatinib; part 2 (1:1:2) control, trastuzumab, or lapatinib and trastuzumab combination. Treatment was given for 11 days presurgery. Coprimary endpoints were change in Ki67 and apoptosis between baseline and surgery tumor samples (biologic response: ≥30% change). Central pathology review scored residual cancer burden (RCB). Relapse-free survival (RFS) explored long-term effects.
Between November 2010 and September 2015, 257 patients were randomized (part 1: control 22, trastuzumab 57, lapatinib 51; part 2: control 29, trastuzumab 32, combination 66). Ki67 response was evaluable for 223 patients: in part 1 Ki67 response occurred in 29/44 (66%) lapatinib versus 18/49 (37%) trastuzumab (P = 0.007) and 1/22 (5%) control (P < 0.0001); in part 2 in 36/49 (74%) combination versus 14/31 (45%) trastuzumab (P = 0.02) and 2/28 (7%) control (P < 0.0001). No significant increase in apoptosis after 11 days was seen in treatment groups. Six patients achieved complete pathologic response (pCR, RCB0) and 13 RCB1, all but two in the combination group. After 6 years median follow-up, 28 (11%) had recurrence and 19 (7%) died. No recurrences or deaths were observed among patients who achieved a pCR. Ki67% falls ≥50% associated with fewer recurrences (P = 0.002).
Early response after short duration anti-HER2 dual therapy identifies cancers dependent on the HER2 pathway providing a strategy for exploring risk-adapted individualized treatment de-escalation.
EPHOS-B 旨在确定围手术期抗 HER2 治疗是否抑制了 HER2 阳性乳腺癌的增殖和/或增加了细胞凋亡。
这是一项随机的、两部分、多中心的Ⅱ期临床试验，纳入了新诊断为 HER2 阳性浸润性乳腺癌且即将接受手术的女性患者。患者被随机分配至：第 1 部分（1:2:2），不治疗（对照组），曲妥珠单抗或拉帕替尼；第 2 部分（1:1:2），对照组、曲妥珠单抗或拉帕替尼联合曲妥珠单抗。治疗在术前进行 11 天。主要终点是肿瘤样本的 Ki67 和凋亡的变化（生物学反应：≥30%的变化）。中心病理学评估了残留癌负荷（RCB）。无复发生存期（RFS）探索了长期效果。
2010 年 11 月至 2015 年 9 月，共 257 名患者被随机分配（第 1 部分：对照组 22 例，曲妥珠单抗组 57 例，拉帕替尼组 51 例；第 2 部分：对照组 29 例，曲妥珠单抗组 32 例，联合组 66 例）。223 名患者可评估 Ki67 反应：第 1 部分，拉帕替尼组 29/44（66%）的 Ki67 反应发生，而曲妥珠单抗组 18/49（37%）（P=0.007）和对照组 1/22（5%）（P＜0.0001）；第 2 部分，联合组 36/49（74%）的 Ki67 反应发生，而曲妥珠单抗组 14/31（45%）（P=0.02）和对照组 2/28（7%）（P＜0.0001）。治疗组在 11 天后没有观察到细胞凋亡的显著增加。6 名患者达到完全病理缓解（pCR，RCB0），13 名患者达到 RCB1，除了两名患者外，其余均来自联合组。中位随访 6 年后，28 名（11%）患者复发，19 名（7%）患者死亡。在达到 pCR 的患者中没有观察到复发或死亡。Ki67%下降≥50%与复发减少相关（P=0.002）。
短时间抗 HER2 双重治疗后的早期反应确定了依赖于 HER2 通路的癌症，为探索风险适应性个体化治疗降级提供了策略。
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