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2015年ASCO年會即將揭幕。6月1日上午的乳腺癌口頭報告專場上，將公布的一項2期臨床研究，評估了12周的新輔助TDM1聯合或不聯合內分泌治療對於HER2陽性激素受體陽性的早期乳腺癌的療效（摘要號506）。醫脈通對此進行了報導。
有證據表明，根據激素受體（HR）狀態不同，標準新輔助化療聯合靶向治療在HER2+早期乳腺癌（eBC）的療效有所不同。ADAPT HER2+/HR+研究旨在確定雙靶向治療的應答者，這一問題也一直沒有得到廣泛的探討。
380例患者（pts）接受12周的新輔助治療。A/B 組：T-DM1(3.6mg/kg q3w）± 內分泌治療（ET）（絕經前：他莫昔芬；絕經後：芳香化酶抑制劑）；C 組（對照組）：q3w曲妥珠單抗+ ET。手術後，患者每周接受4xEC–12x 紫杉醇（調查人員自由裁量）並完成1年曲妥珠單抗治療。試驗檢測A和B 組患者的 pCR（達到yPN0 和 ypT0），檢測值與C 組比較。生物標記物在基線和3周後測量。
預先計劃中期分析（N=130）的目的是確定一個早應答的生物標記物（如Ki-67的下降），並驗證試驗的假設。患者中位年齡為49歲；55%為絕經前的患者；40%患者的腫瘤為cT1，51% 為cT2; 68% 為cN0，27%為cN1; 75%為G3。Ki67為中位基線的佔30%。三組患者中，95－100%的患者接受了全部4個周期的治療。12例患者（A組4例; B組6例; C組2例）中發生了15件嚴重不良事件，大多數是CTC2級（9例）或3級（4例）；所有患者完全恢復，無後遺症。
總pCR 率為30.8%：A、B和C三組分別為40.5%、45.8%和6.7％。A或B與C組之間的差異是具有統計學意義的（p< 0.001），但A、B兩組間差異不大。探索性分析表明，對於絕經前患者，在T-DM1中加入內分泌治療 是有益處的(pCR:單藥T-DM1為28.6% vs. T-DM1＋ET為47.6%)，但這對於絕經後患者卻不是如此（pCR: 64.3% vs. 50%）。有43.1%的患者3周內活檢時不可能實現Ki-67的定量，主要是由於低腫瘤細胞計數（< 500）；其餘的腫瘤中，治療一周期後，有21.6%（16/74）的腫瘤中Ki-67≤10%。這些結果也可能受不同內分泌治療選擇（Tam vs. AI）而影響，仍然需要最終的數據來證實。
中期分析首次證明了，對於HER2+/HR+早期乳腺癌患者，僅12周的T-DM1±ET（沒有全身化療）獲得的pCR 率（> 40%）具有臨床意義。正在進行的生物標記物分析包括PI3K突變和內在的亞型。在2015年1月，有449例患者完成註冊。臨床試驗信息：NCT01745965
更多精彩內容》》》2015年ASCO年會專題報導
網址http://meeting.medlive.cn/detail/index-8531.html
摘要原文（摘要號506）
Background: Evidence suggests differential efficacy of standard neoadjuvant chemo- + targeted therapy in HER2+ early breast cancer (eBC) according to hormone-receptor (HR) status. ADAPT HER2+/HR+ aims to identify responders to dual targeted therapy, which has not been widely explored.
Methods: 380 patients (pts) receive 12 weeks of neoadjuvant therapy. Arms A/B: T-DM1 (3.6 mg/kg q3w) ± endocrine therapy (ET) (pre-: tamoxifen; postmenopausal: aromatase inhibitor); Arm C (control): q3w trastuzumab + ET. After surgery, pts are to receive 4xEC – 12xpaclitaxel weekly (investigators』 discretion) and complete 1y trastuzumab. Trial tests pCR (yPN0 and ypT0/is) in Arms A and B compared to control (C). Biomarkers are measured at baseline and after 3 weeks.
Results: Pre-planned interim analysis (n = 130) aimed to identify an early-response biomarker (e.g. Ki-67 drop) and to validate trial assumptions. Median age was 49 years; 55% were pre-menopausal; 40% had cT1 tumors, 51% cT2; 68% had cN0, 27% cN1; 75% had G3. Median baseline Ki67 was 30%. In all arms, 95-100% received all 4 therapy cycles. 15 SAEs occurred in 12 pts (A:4; B:6; C:2), majority are CTC grades 2 (9) or 3 (4); all pts completely recovered without sequelae. Overall pCR rate was 30.8%: A: 40.5%, B: 45.8%, C: 6.7%. The difference between either arm A or B vs. C was significant (p < 0.001), but not A vs. B. Exploratory analysis suggests benefit of adding ET to T-DM1 in pre- (pCR: 28.6% for T-DM1 single agent vs. 47.6% with ET) but not in postmenopausal pts (pCR: 64.3% vs. 50%). Ki-67 quantification in the 3-week biopsy was not possible in 43.1%, mostly due to low tumor cell counts ( < 500); of the remaining tumors, 21.6% (16/74) had Ki-67 ≤ 10% after first cycle. Final data set is required to substantiate these findings which may also be impacted by the different ET options (Tam vs. AI).
Conclusions: The interim analysis demonstrates for the first time clinically meaningful pCR rates ( > 40%) after only 12 weeks of T-DM1 ± ET without systemic chemotherapy in HER2+/HR+ eBC. Ongoing biomarker analyses include PI3K mutations and intrinsic subtypes. In 1/2015, registration phase was completed at 449 pts. Clinical trial information: NCT01745965
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