阿妥珠單抗聯合nab紫杉醇和蒽環類化療治療早期三陰性乳腺癌療效顯著
作者：
小柯機器人發布時間：2020/9/22 14:33:50
美國布列根和婦女癌症中心Elizabeth A Mittendorf團隊研究了阿妥珠單抗聯合nab紫杉醇和蒽環類化療的新輔助治療對早期三陰性乳腺癌的治療效果。2020年9月20日，該研究發表在《柳葉刀》雜誌上。
早期三陰性乳腺癌（TNBC）的首選新輔助治療方案包括蒽環類環磷醯胺和紫杉烷類化療。研究組比較了阿妥珠單抗與安慰劑聯合nab紫杉醇，阿黴素聯合環磷醯胺作為早期TNBC新輔助治療的有效性和安全性。
研究組進行了一項雙盲、隨機、臨床3期研究，在13個國家的75個學術和社區點招募18歲及以上且組織學上記錄有TNBC的患者。將其按1：1隨機分組，分別接受化療加靜脈注射阿妥珠單抗或安慰劑，每2周一次。採用nab紫杉醇、阿黴素、環磷醯胺進行化療，之後進行手術。共同主要終點是所有隨機人群和PD-L1陽性人群的病理完全緩解。
2017年7月7日至2019年9月24日，研究組共招募了455名患者並對其進行資格評估。在333名符合條件的患者中，165名被隨機分配接受阿妥珠單抗聯合化療，168名接受安慰劑聯合化療。截至2020年4月3日，阿妥珠單抗聯合化療組的中位隨訪時間為20.6個月，安慰劑聯合化療組為19.8個月。
阿妥珠單抗聯合化療組中有95例（58%）患者病理完全緩解，安慰劑聯合化療組中有69例（41%），差異顯著。在PD-L1陽性人群中，阿妥珠單抗聯合化療組中有69%的患者獲病理完全緩解，安慰劑聯合化療組中有49%，差異亦顯著。在新輔助治療階段，兩組間3-4級不良事件發生率相似，分別有37例（23%）和26例（16%）患者發生與治療相關的嚴重不良事件，每組各有1名患者發生治療無關的5級不良事件。
研究結果表明，對於早期TNBC患者，阿妥珠單抗聯合nab紫杉醇和蒽環類化療的新輔助治療可顯著提高患者的病理完全緩解率，且安全耐受。
附：英文原文
Title: Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial
Author: Elizabeth A Mittendorf, Hong Zhang, Carlos H Barrios, Shigehira Saji, Kyung Hae Jung, Roberto Hegg, Andreas Koehler, Joohyuk Sohn, Hiroji Iwata, Melinda L Telli, Cristiano Ferrario, Kevin Punie, Frédérique Penault-Llorca, Shilpen Patel, Anh Nguyen Duc, Mario Liste-Hermoso, Vidya Maiya, Luciana Molinero, Stephen Y Chui, Nadia Harbeck
Issue&Volume: 2020-09-20
Abstract:
Background
Preferred neoadjuvant regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. IMpassion031 compared efficacy and safety of atezolizumab versus placebo combined with nab-paclitaxel followed by doxorubicin plus cyclophosphamide as neoadjuvant treatment for early-stage TNBC.
Methods
This double-blind, randomised, phase 3 study enrolled patients in 75 academic and community sites in 13 countries. Patients aged 18 years or older with previously untreated stage II–III histologically documented TNBC were randomly assigned (1:1) to receive chemotherapy plus intravenous atezolizumab at 840 mg or placebo every 2 weeks. Chemotherapy comprised of nab-paclitaxel at 125 mg/m 2 every week for 12 weeks followed by doxorubicin at 60 mg/m 2 and cyclophosphamide at 600 mg/m 2 every 2 weeks for 8 weeks, which was then followed by surgery. Stratification was by clinical breast cancer stage and programmed cell death ligand 1 (PD-L1) status. Co-primary endpoints were pathological complete response in all-randomised (ie, all randomly assigned patients in the intention-to-treat population) and PD-L1-positive (ie, patients with PD-L1-expressing tumour infiltrating immune cells covering ≥1% of tumour area) populations. This study is registered with ClinicalTrials.gov ( NCT03197935), Eudra (CT2016-004734-22), and the Japan Pharmaceutical Information Center (JapicCTI-173630), and is ongoing.
Findings
Between July 7, 2017, and Sept 24, 2019, 455 patients were recruited and assessed for eligibility. Of the 333 eligible patients, 165 were randomly assigned to receive atezolizumab plus chemotherapy and 168 to placebo plus chemotherapy. At data cutoff (April 3, 2020), median follow-up was 20·6 months (IQR 8·7–24·9) in the atezolizumab plus chemotherapy group and 19·8 months (8·1–24·5) in the placebo plus chemotherapy group. Pathological complete response was documented in 95 (58%, 95% CI 50–65) patients in the atezolizumab plus chemotherapy group and 69 (41%, 34–49) patients in the placebo plus chemotherapy group (rate difference 17%, 95% CI 6–27; one-sided p=0·0044 [significance boundary 0·0184]). In the PD-L1-positive population, pathological complete response was documented in 53 (69%, 95% CI 57–79) of 77 patients in the atezolizumab plus chemotherapy group versus 37 (49%, 38–61) of 75 patients in the placebo plus chemotherapy group (rate difference 20%, 95% CI 4–35; one-sided p=0·021 [significance boundary 0·0184]). In the neoadjuvant phase, grade 3–4 adverse events were balanced and treatment-related serious adverse events occurred in 37 (23%) and 26 (16%) patients, with one patient per group experiencing an unrelated grade 5 adverse event (traffic accident in the atezolizumab plus chemotherapy group and pneumonia in the placebo plus chemotherapy group).
Interpretation
In patients with early-stage TNBC, neoadjuvant treatment with atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy significantly improved pathological complete response rates with an acceptable safety profile.
DOI: 10.1016/S0140-6736(20)31953-X
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31953-X/fulltext