Merck’s Keytruda Notches Win in First-Line Cervical Cancer

默克公司Keytruda Notches在一线宫颈癌中获胜

2021-10-14 22:30:07 BioSpace


Kena Betancur/Getty Images Merck's bestselling, blockbuster checkpoint inhibitor Keytruda (pembrolizumab) picked up yet another indication, this time with chemotherapy, with or without bevacizumab, for persistent, recurrent or metastatic cervical cancer. These tumors express PD-L1 as determined by an assay approved by the U.S. Food and Drug Administration (FDA).  Keytruda is one of the most tested, if not the most tested, drugs in the industry, with more than 1,600 clinical trials ongoing currently. The company had six specific announcements related to the drug since the beginning of September, not including the FDA’s approval on August 31 for the drug for first-line advanced urothelial (bladder) carcinoma. That announcement was a conversion from an accelerated to a full (regular) approval.  Others include its approval in China in combination with chemotherapy for first-line locally advanced unresectable or metastatic esophageal or gastroesophageal junction (GEJ) carcinoma; a positive recommendation in Europe for Keytruda with chemotherapy in locally recurrent unresectable or metastatic triple-negative breast cancer; full results from the Phase III KEYNOTE-826 trial of the drug with chemotherapy with or without bevacizumab for first-line treatment of persistent, recurrent or metastatic cervical cancer; first results from the Phase III KEYNOTE-716 trial, where the drug as adjuvant treatment demonstrated statistically significant and clinically meaningful improvement in recurrence-free survival in resected high-risk stage II melanoma; and more. Today’s approval was based on the Phase III KEYNOTE-826 trial that evaluated Keytruda and chemotherapy (paclitaxel plus cisplatin or paclitaxel plus carboplatin) with or without bevacizumab compared to the same chemotherapy treatment, with or without bevacizumab. The treatment with Keytruda demonstrated superior overall survival (OS) and progression-free survival (PFS) in patients whose tumors expressed PD-L1.  Also, more patients responded to the Keytruda-chemotherapy than to chemotherapy alone, with an objective response rate (ORR) of 68%. In patients who responded, the median duration of response (DOR) was 18 months for the Keytruda-chemo group and 10.4 months for chemotherapy, with or without bevacizumab. Not only was this study for first-line advanced cervical cancer, but as mentioned above, it was a confirmatory trial for its accelerated approval for cervical cancer. This allowed the FDA to convert the accelerated approval over to a standard approval. KEYNOTE-826 enrolled 617 patients with persistent, recurrent or first-line metastatic cervical cancer who had not received chemotherapy except when used concurrently as a radio-sensitizing agent. They were enrolled no matter what their PD-L1 expression was. However, patients were ineligible who had autoimmune disease requiring systemic therapy within two years of treatment or a condition requiring immunosuppression. Patients were randomized by metastatic status at initial diagnosis and their physician decided whether to use bevacizumab and PD-L1 status. Bevacizumab is Genentech’s Avastin. “Cervical cancer more commonly affects younger women and certain women of color in the U.S., and unfortunately, women diagnosed with persistent, recurrent or metastatic cervical cancer often have a low survival rate,” said Bradley Monk, oncologist with Arizona Oncology, medical director of U.S. Oncology Research Gynecology Program and Professor of Obstetrics and Gynecology at University of Arizona's College of Medicine and Creighton University School of Medicine. “There have been no first-line approvals for women with persistent, recurrent or metastatic cervical cancer in the past seven years. I am excited for today’s approval of a new combination with Keytruda, which offers a new treatment option for appropriate patients.” Roy Baynes, Merck Research Laboratories’ Senior Vice President and Head of Global Clinical Development and Chief Medical Officer, noted that, “Today’s news is a meaningful step forward, as it offers a new therapeutic option for these patients and reinforces the role of Keytruda in treating certain types of cervical cancers, with a second indication for the disease. The data showing a 36% reduction in the risk of death are compelling, and this approval brings an important new first-line treatment option to women with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1.”
Kena Betancur/Getty Images 默克公司最畅销、轰动一时的检查点抑制剂Keytruda(彭布罗利珠单抗)获得了另一个适应症,这一次是化疗,无论是否贝伐单抗,都适用于持续性、复发性或转移性宫颈癌。这些肿瘤表达PD-L1,由美国食品药品监督管理局(FDA)批准的分析确定。 Keytruda是业内测试最多的药物之一,目前正在进行1600多项临床试验。自9月初以来,该公司已经发布了六项与该药物相关的具体公告,不包括美国食品和药物管理局8月31日批准该药物用于一线晚期尿路上皮(膀胱)癌。这一宣布是从加速批准到全面(定期)批准的转换。 其他包括在中国批准与化疗联合治疗一线局部晚期、不可切除或转移性食管或胃食管交界区(GEJ)癌;欧洲对Keytruda联合化疗治疗局部复发、不可切除或转移的三阴性乳腺癌的积极推荐;该药物与化疗联合或不联合贝伐单抗一线治疗持续性、复发性或转移性宫颈癌的III期KEYNOTE-826试验的全部结果;来自III期KEYNOTE-716试验的第一个结果,在该试验中,药物作为辅助治疗证明了在切除的高风险II期黑色素瘤的无复发生存率方面有统计学意义和临床意义;还有更多。 今天的批准是基于III期KEYNOTE-826试验,该试验评估了Keytruda和化疗(紫杉醇加顺铂或紫杉醇加卡铂)加或不加贝伐单抗与相同化疗治疗加或不加贝伐单抗的比较。在肿瘤表达PD-L1的患者中,Keytruda的治疗显示出优越的总生存期(OS)和无进展生存期(PFS)。 此外,更多的患者对Keytruda化疗的反应比单纯化疗,客观反应率(ORR)为68%。在有反应的患者中,Keytruda化疗组的中位反应持续时间(DOR)为18个月,化疗组为10.4个月,无论有无贝伐单抗。 这项研究不仅用于一线晚期宫颈癌,而且如上所述,它是一项验证性试验,加速了宫颈癌的批准。这使得FDA可以将加速批准转换为标准批准。 KEYNOTE-826纳入了617名持续、复发或一线转移性宫颈癌患者,他们没有接受过化疗,除非同时作为放射增敏剂使用。无论PD-L1的表达是什么,他们都被登记。然而,在治疗后两年内患有需要全身治疗的自身免疫性疾病或需要免疫抑制的患者是不符合条件的。患者在最初诊断时根据转移状态随机分组,他们的医生决定是否使用贝伐单抗和PD-L1状态。贝伐单抗是基因泰克的阿瓦斯丁。 亚利桑那州肿瘤学家布拉德利·蒙克(Bradley Monk)说:“宫颈癌更常见地影响美国的年轻女性和某些有色人种女性,不幸的是,被诊断为持续性、复发性或转移性宫颈癌的女性通常存活率很低。”布拉德利·蒙克是亚利桑那州肿瘤学家、美国肿瘤研究妇科项目医学主任、亚利桑那州大学医学院和克莱顿大学医学院妇产科教授。“在过去的七年里,没有针对持续性、复发性或转移性宫颈癌妇女的一线批准。我对今天批准与Keytruda的新组合感到兴奋,这为适当的患者提供了一种新的治疗选择。“ 默克研究实验室高级副总裁兼全球临床开发负责人兼首席医疗官罗伊·贝恩斯(Roy Baynes)指出,“今天的消息是向前迈出的有意义的一步,因为它为这些患者提供了一种新的治疗选择,并加强了Keytruda在治疗某些类型宫颈癌方面的作用,为该疾病提供了第二个适应症。显示死亡风险降低36%的数据令人信服,这一批准为肿瘤表达PD-L1的持续性、复发性或转移性宫颈癌妇女带来了一个重要的新的一线治疗选择。“