Sekulic Aleksandar, Migden Michael R, Basset-Seguin Nicole, Garbe Claus, Gesierich Anja, Lao Christopher D, Miller Chris, Mortier Laurent, Murrell Dedee F, Hamid Omid, Quevedo Jorge F, Hou Jeannie, McKenna Edward, Dimier Natalie, Williams Sarah, Schadendorf Dirk, Hauschild Axel
Mayo Clinic Scottsdale, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA.
Departments of Dermatology and Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA.
BMC Cancer. 2017 May 16;17(1):332. doi: 10.1186/s12885-017-3286-5.
In the primary analysis of the ERIVANCE BCC trial, vismodegib, the first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed objective response rates (ORRs) by independent review facility (IRF) of 30% and 43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC), respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC). Herein, we present long-term safety and final investigator-assessed efficacy results in patients with mBCC or laBCC.
One hundred four patients with measurable advanced BCC received oral vismodegib 150 mg once daily until disease progression or intolerable toxicity. The primary end point was IRF-assessed ORR. Secondary end points included ORR, duration of response (DOR), progression-free survival, overall survival (OS), and safety.
At data cutoff (39 months after completion of accrual), 8 patients were receiving the study drug (69 patients in survival follow-up). Investigator-assessed ORR was 48.5% in the mBCC group (all partial responses) and 60.3% in the laBCC group (20 patients had complete response and 18 patients had partial response). ORRs were comparable across patient subgroups, including aggressive histologic subtypes (eg, infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC). Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC cohort. Adverse events remained consistent with clinical experience. Thirty-three deaths (31.7%) were reported; none were related to vismodegib.
This long-term update of the ERIVANCE BCC trial demonstrated durability of response, efficacy across patient subgroups, and manageable long-term safety of vismodegib in patients with advanced BCC.
This study was registered prospectively with Clinicaltrials.gov , number NCT00833417 on January 30, 2009.
在ERIVANCE BCC试验的初步分析中，维莫德吉（vismodegib）作为美国食品药品监督管理局批准的首个刺猬通路抑制剂，在转移性基底细胞癌（mBCC）和局部晚期基底细胞癌（laBCC）中，经独立审查机构（IRF）评估的客观缓解率（ORR）分别为30%和43%。经研究者评估的ORR在mBCC中为45%，在laBCC中为60%。在此，我们展示了mBCC或laBCC患者的长期安全性以及研究者最终评估的疗效结果。
104例可测量的晚期基底细胞癌患者每日口服一次150毫克维莫德吉，直至疾病进展或出现无法耐受的毒性。主要终点为IRF评估的ORR。次要终点包括ORR、缓解持续时间（DOR）、无进展生存期、总生存期（OS）和安全性。
在数据截止时（入组完成后39个月），8例患者仍在接受研究药物治疗（69例患者处于生存随访中）。研究者评估的ORR在mBCC组为48.5%（均为部分缓解），在laBCC组为60.3%（20例患者完全缓解，18例患者部分缓解）。各患者亚组的ORR相当，包括侵袭性组织学亚型（如浸润性基底细胞癌）。mBCC的中位DOR为14.8个月，laBCC为26.2个月。mBCC队列的中位OS为33.4个月，laBCC队列无法估计。不良事件与临床经验一致。报告了33例死亡（31.7%）；均与维莫德吉无关。
ERIVANCE BCC试验的这一长期更新显示了维莫德吉在晚期基底细胞癌患者中的缓解持久性、各患者亚组的疗效以及可控的长期安全性。
本研究于2009年1月30日在Clinicaltrials.gov上进行了前瞻性注册，编号为NCT00833417。
