Swain Sandra M, Baselga José, Kim Sung-Bae, Ro Jungsil, Semiglazov Vladimir, Campone Mario, Ciruelos Eva, Ferrero Jean-Marc, Schneeweiss Andreas, Heeson Sarah, Clark Emma, Ross Graham, Benyunes Mark C, Cortés Javier
The authors' affiliations are listed in the Appendix.
N Engl J Med. 2015 Feb 19;372(8):724-34. doi: 10.1056/NEJMoa1413513.
In patients with metastatic breast cancer that is positive for human epidermal growth factor receptor 2 (HER2), progression-free survival was significantly improved after first-line therapy with pertuzumab, trastuzumab, and docetaxel, as compared with placebo, trastuzumab, and docetaxel. Overall survival was significantly improved with pertuzumab in an interim analysis without the median being reached. We report final prespecified overall survival results with a median follow-up of 50 months.
We randomly assigned patients with metastatic breast cancer who had not received previous chemotherapy or anti-HER2 therapy for their metastatic disease to receive the pertuzumab combination or the placebo combination. The secondary end points of overall survival, investigator-assessed progression-free survival, independently assessed duration of response, and safety are reported. Sensitivity analyses were adjusted for patients who crossed over from placebo to pertuzumab after the interim analysis.
The median overall survival was 56.5 months (95% confidence interval [CI], 49.3 to not reached) in the group receiving the pertuzumab combination, as compared with 40.8 months (95% CI, 35.8 to 48.3) in the group receiving the placebo combination (hazard ratio favoring the pertuzumab group, 0.68; 95% CI, 0.56 to 0.84; P<0.001), a difference of 15.7 months. This analysis was not adjusted for crossover to the pertuzumab group and is therefore conservative. Results of sensitivity analyses after adjustment for crossover were consistent. Median progression-free survival as assessed by investigators improved by 6.3 months in the pertuzumab group (hazard ratio, 0.68; 95% CI, 0.58 to 0.80). Pertuzumab extended the median duration of response by 7.7 months, as independently assessed. Most adverse events occurred during the administration of docetaxel in the two groups, with long-term cardiac safety maintained.
In patients with HER2-positive metastatic breast cancer, the addition of pertuzumab to trastuzumab and docetaxel, as compared with the addition of placebo, significantly improved the median overall survival to 56.5 months and extended the results of previous analyses showing the efficacy of this drug combination. (Funded by F. Hoffmann-La Roche and Genentech; CLEOPATRA ClinicalTrials.gov number, NCT00567190.).
在人表皮生长因子受体2（HER2）阳性的转移性乳腺癌患者中，与安慰剂、曲妥珠单抗和多西他赛相比，一线使用帕妥珠单抗、曲妥珠单抗和多西他赛治疗后，无进展生存期显著改善。在一项中期分析中，帕妥珠单抗显著改善了总生存期，且未达到中位数。我们报告了最终预先设定的总生存期结果，中位随访时间为50个月。
我们将未接受过针对转移性疾病的先前化疗或抗HER2治疗的转移性乳腺癌患者随机分配接受帕妥珠单抗联合治疗或安慰剂联合治疗。报告了总生存期、研究者评估的无进展生存期、独立评估的缓解持续时间和安全性等次要终点。对中期分析后从安慰剂组交叉到帕妥珠单抗组的患者进行了敏感性分析调整。
接受帕妥珠单抗联合治疗组的中位总生存期为56.5个月（95%置信区间[CI]，49.3至未达到），而接受安慰剂联合治疗组为40.8个月（95%CI，35.8至48.3）（有利于帕妥珠单抗组的风险比为0.68；95%CI，0.56至0.84；P<0.001），相差15.7个月。该分析未对交叉到帕妥珠单抗组进行调整，因此较为保守。调整交叉后的敏感性分析结果一致。研究者评估的帕妥珠单抗组中位无进展生存期改善了6.3个月（风险比，0.68；95%CI，0.58至0.80）。经独立评估，帕妥珠单抗将中位缓解持续时间延长了7.7个月。两组中大多数不良事件发生在多西他赛给药期间，长期心脏安全性得以维持。
在HER2阳性转移性乳腺癌患者中，与添加安慰剂相比，在曲妥珠单抗和多西他赛中添加帕妥珠单抗可显著将中位总生存期提高至56.5个月，并扩展了先前分析显示该药物组合疗效的结果。（由F. Hoffmann-La Roche和Genentech资助；CLEOPATRA临床试验注册号，NCT00567190。）
