辉瑞曲妥珠一线治疗转移性乳腺癌
前情提要
2018年12月20日，英国癌症研究基金会和英国《自然》旗下《英国癌症杂志》在线发表美国辉瑞、斯坦福大学、佛罗里达癌症研究所、乌克兰第聂伯罗彼得罗夫斯克医学院、巴西巴雷图斯肿瘤医院、印度迪纳纳特曼吉什卡尔医院、日本熊本大学、俄罗斯彼得罗夫肿瘤研究所、韩国国家癌症中心、菲律宾圣路加医疗中心、波兰波美拉尼亚省肿瘤医院的双盲随机对照研究报告，对辉瑞曲妥珠单抗仿制药＋紫杉醇、罗氏曲妥珠单抗原研药＋紫杉醇一线治疗HER2阳性转移性乳腺癌进行了比较。
REFLECTIONS B327-02: A Study Of PF-05280014 [Trastuzumab-Pfizer] Or Herceptin [Trastuzumab-EU] Plus Paclitaxel In HER2 Positive First Line Metastatic Breast Cancer Treatment (NCT01989676)
该国际多中心双盲随机对照研究于2014年4月4日～2016年1月22日入组HER2阳性转移性乳腺癌患者707例，按1∶1随机分组接受静脉注射辉瑞曲妥珠单抗＋紫杉醇（352例）或罗氏曲妥珠单抗＋紫杉醇（355例）。曲妥珠单抗首次4mg / kg，随后每周2mg / kg，也可选择从第33周改为每3周6mg / kg，直至疾病进展。紫杉醇首次80mg / m²，随后每个周期28天的第1、8、15天用药，至少6个周期或直至最大缓解获益。主要终点为客观缓解率，评估第25周获得缓解情况，并于第33周确认，由放射科医师集中盲法复核。预设客观缓解率风险比的95%置信区间落入0.80～1.25为统计学等效。
结果，截至2017年1月11日随机分组后378天的数据，辉瑞曲妥珠单抗（PF-05280014）组与罗氏曲妥珠单抗（赫赛汀）组相比：
客观缓解率等效：62.5%比66.5%（风险比：0.940，95%置信区间：0.842～1.049）
中位无进展生存：12.16比12.06个月
一年无进展生存：54%比51%（0.505）
中位总生存相似：两组均未达到半数死亡
一年总生存相似：89.31%比87.36%（P=0.507）
安全性结局和免疫原性相似
因此，该研究结果表明，对于一线治疗HER2阳性转移性乳腺癌，辉瑞曲妥珠单抗＋紫杉醇与罗氏曲妥珠单抗＋紫杉醇的客观缓解率等效，无进展生存、总生存、安全性结局、免疫原性相似。
Br J Cancer. 2018 Dec 20. [Epub ahead of print]
PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study.
Mark D. Pegram, Igor Bondarenko, Marina Moreira Costa Zorzetto, Sachin Hingmire, Hirotaka Iwase, Petr V. Krivorotko, Keun Seok Lee, Rubi K. Li, Joanna Pikiel, Rajesh Aggarwal, Reginald Ewesuedo, Amy Freyman, Ray Li, Alicia Vana, Donghua Yin, Charles Zacharchuk, Elizabeth Tan-Chiu.
Stanford University School of Medicine, Stanford, CA, USA; Dnipropetrovsk Medical Academy, Dnipro, Ukraine; Barretos Cancer Hospital, Sao Paulo, Brazil; Deenanath Mangeshkar Hospital and Research Centre, Erandawne, Pune, Maharashtra, India; Kumamoto University Graduate School of Medical Science, Kumamoto, Japan; Petrov Research Institute of Oncology, Saint Petersburg, Russian; National Cancer Center, Goyang-si, Gyeonggi-do, Korea; St. Luke's Medical Center, Quezon City, Metro Manila, Philippines; Wojewódzkie Centrum Onkologii, Gdańsk, Poland; Pfizer Inc, New York, NY, USA; Pfizer Inc, Cambridge, MA, USA; Pfizer Inc, San Diego, CA, USA; Florida Cancer Research Institute, Plantation, FL, USA.
BACKGROUND: This randomised, double-blind study compared PF-05280014 (a trastuzumab biosimilar) with reference trastuzumab (Herceptin) sourced from the European Union (trastuzumab-EU), when each was given with paclitaxel as first-line treatment for HER2-positive metastatic breast cancer.
METHODS: Between 4 April 2014 and 22 January 2016, 707 participants were randomised 1:1 to receive intravenous PF-05280014 plus paclitaxel (PF-05280014 group; n=352) or trastuzumab-EU plus paclitaxel (trastuzumab-EU group; n=355). PF-05280014 or trastuzumab-EU was administered weekly (first dose 4mg/kg, subsequent doses 2mg/kg), with the option to change to a 3-weekly regimen (6mg/kg) from Week 33. Treatment with PF-05280014 or trastuzumab-EU could continue until disease progression. Paclitaxel (starting dose 80mg/m²) was administered on Days 1, 8 and 15 of 28-day cycles for at least six cycles or until maximal benefit of response. The primary endpoint was objective response rate (ORR), evaluating responses achieved by Week 25 and confirmed by Week 33, based on blinded central radiology review.
RESULTS: The risk ratio for ORR was 0.940 (95% CI: 0.842-1.049). The 95% CI fell within the pre-specified equivalence margin of 0.80-1.25. ORR was 62.5% (95% CI: 57.2-67.6%) in the PF-05280014 group and 66.5% (95% CI: 61.3-71.4%) in the trastuzumab-EU group. As of data cut-off on 11 January 2017 (using data up to 378 days post-randomisation), there were no notable differences between groups in progression-free survival (median: 12.16 months in the PF-05280014 group vs. 12.06 months in the trastuzumab-EU group; 1-year rate: 54% vs. 51%) or overall survival (median: not reached in either group; 1-year rate: 89.31% vs. 87.36%). Safety outcomes and immunogenicity were similar between the treatment groups.
CONCLUSION: When given as first-line treatment for HER2-positive metastatic breast cancer, PF-05280014 plus paclitaxel demonstrated equivalence to trastuzumab-EU plus paclitaxel in terms of ORR.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01989676
DOI: 10.1038/s41416-018-0340-2
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