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【NEJM】Iniparib联合化疗治疗转移性三阴性乳腺癌
O'Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C.
N Engl J Med. 2011 Jan 5. [Epub ahead of print]
http://www.nejm.org/doi/full/10.1056/NEJMoa1011418
Background Triple-negative breast cancers have inherent defects in DNA repair, making this cancer a rational target for therapy based on poly(adenosine diphosphate–ribose) polymerase (PARP) inhibition.
Methods We conducted an open-label, phase 2 study to compare the efficacy and safety of gemcitabine and carboplatin with or without iniparib, a small molecule with PARP-inhibitory activity, in patients with metastatic triple-negative breast cancer. A total of 123 patients were randomly assigned to receive gemcitabine (1000 mg per square meter of body-surface area) and carboplatin (at a dose equivalent to an area under the concentration–time curve of 2) on days 1 and 8 — with or without iniparib (at a dose of 5.6 mg per kilogram of body weight) on days 1, 4, 8, and 11 — every 21 days. Primary end points were the rate of clinical benefit (i.e., the rate of objective response [complete or partial response] plus the rate of stable disease for ≥6 months) and safety. Additional end points included the rate of objective response, progression-free survival, and overall survival.
Results The addition of iniparib to gemcitabine and carboplatin improved the rate of clinical benefit from 34% to 56% (P=0.01) and the rate of overall response from 32% to 52% (P=0.02). The addition of iniparib also prolonged the median progression-free survival from 3.6 months to 5.9 months (hazard ratio for progression, 0.59; P=0.01) and the median overall survival from 7.7 months to 12.3 months (hazard ratio for death, 0.57; P=0.01). The most frequent grade 3 or 4 adverse events in either treatment group included neutropenia, thrombocytopenia, anemia, fatigue or asthenia, leukopenia, and increased alanine aminotransferase level. No significant difference was seen between the two groups in the rate of adverse events.
Conclusions The addition of iniparib to chemotherapy improved the clinical benefit and survival of patients with metastatic triple-negative breast cancer without significantly increased toxic effects. On the basis of these results, a phase 3 trial adequately powered to evaluate overall survival and progression-free survival is being conducted. (Funded by BiPar Sciences [now owned by Sanofi-Aventis]; ClinicalTrials.gov number, NCT00540358.)
py in Metastatic Triple-Negative Breast Cancer.pdf (581.72k) 在线查看 Iniparib plus Chemotherapy in Metastatic Triple-Negative Breast Cancer
Iniparib联合化疗治疗转移性三阴性乳腺癌
Background Triple-negative breast cancers have inherent defects in DNA repair, making this cancer a rational target for therapy based on poly(adenosine diphosphate–ribose) polymerase (PARP) inhibition.
背景：三阴性乳腺癌的DNA修复功能存在先天缺陷，这使其成为多聚二磷酸腺苷核糖聚合酶（PARP）抑制剂的治疗靶标。
Methods We conducted an open-label, phase 2 study to compare the efficacy and safety of gemcitabine and carboplatin with or without iniparib, a small molecule with PARP-inhibitory activity, in patients with metastatic triple-negative breast cancer. A total of 123 patients were randomly assigned to receive gemcitabine (1000 mg per square meter of body-surface area) and carboplatin (at a dose equivalent to an area under the concentration–time curve of 2) on days 1 and 8 — with or without iniparib (at a dose of 5.6 mg per kilogram of body weight) on days 1, 4, 8, and 11 — every 21 days. Primary end points were the rate of clinical benefit (i.e., the rate of objective response [complete or partial response] plus the rate of stable disease for ≥6 months) and safety. Additional end points included the rate of objective response, progression-free survival, and overall survival.
方法：我们进行了一项开放式、Ⅱ期临床，比较吉西他滨+卡铂联合和不联合iniparib（一种小分子PARP抑制剂）治疗转移性三阴性乳腺癌。共计123例患者，随机分组接受吉西他滨（1000 mg/m2）+卡铂（AUC 2）(d1,8)联合和不联合iniparib（5.6 mg/kg）（d1,4,8,11）治疗，21天一疗程。主要研究终点为临床受益率（例如客观有效率（CR或PR）、SD≥6月的比率等）和安全性。额外研究终点包括客观有效率、无病生存（PFS）和总生存（OS）。
Results The addition of iniparib to gemcitabine and carboplatin improved the rate of clinical benefit from 34% to 56% (P=0.01) and the rate of overall response from 32% to 52% (P=0.02). The addition of iniparib also prolonged the median progression-free survival from 3.6 months to 5.9 months (hazard ratio for progression, 0.59; P=0.01) and the median overall survival from 7.7 months to 12.3 months (hazard ratio for death, 0.57; P=0.01). The most frequent grade 3 or 4 adverse events in either treatment group included neutropenia, thrombocytopenia, anemia, fatigue or asthenia, leukopenia, and increased alanine aminotransferase level. No significant difference was seen between the two groups in the rate of adverse events.
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作者:admin@医学,生命科学 2011-01-10 20:01
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