ASCO 2015 anit-PD-1 药物的新临床结果

The most advanced data came from a pivotal Phase III study of Bristol-Myers' Opdivo (nivolumab) which bested chemotherapy in non-squamous, non-small cell lung cancer--the most common form of lung cancer. Opdivo was approved for advanced squamous NSCLC back in the spring as Bristol-Myers seized an early lead over Merck in the all-important lung cancer market.

Previously treated patients in the Opdivo arm of the Checkmate-057 study demonstrated a 19.2% response rate, compared to 12.4% for docetaxel. Responses were considerably more durable for Opdivo--an average of 17.1 months vs. 5.6 months--while the median overall survival rate hit 12.2 months in the nivolumab group compared to 9.4 months in the docetaxel group.

Investigators also highlighted that a subgroup of patients identified with high levels of PD-L1 in their tumor were particularly responsive, with the median survival rate for nivolumab beating 17 months, compared to 9 months for those treated with docetaxel.

"This marks the end of the chemotherapy era in second-line treatment of lung cancer," Bristol-Myers' Fouad Namouni told Reuters.

Namouni added that Bristol-Myers will be taking its case for a broader approval of the drug to the FDA, where it's likely to be eagerly awaited. The agency was quick to hand out its first approval for lung cancer and shows no signs of slowing down now.

But the data weren't all in Opdivo's favor. Seamus Fernandez at Leerink wrote today that he was distinctly "disappointed" by the overall hazard ratio of 0.73 in the study, with benefits clearly skewing away from patients whose tumors expressed low levels of PD-L1. That kind of distinction could play in favor of Merck and Roche ($RHHBY), which is coming up close behind the two leaders in the field with a biomarker approach to IO.

Evercore ISI's Mark Schoenebaum also notes that conversely patients with low levels of PD-L1 were far less likely to benefit from Bristol's drug. That "raises questions, including whether patients with non-squamous lung cancer in the 2nd line setting would (rather than simply just taking Opdivo) want to have their tumor tested for PDL1 expression before starting PD1 or PDL1 antibodies. In such a scenario, if a patient is willing to undergo a biopsy (which has some risk - small but real) the possibility arises that patients choose a diagnostic assay and antibody from a different company, such as MRK and Roche," Schoenebaum wrote in a note to investors.

A few weeks ago Roche outlined positive Phase II data for its checkpoint inhibitor MPDL3280A, which scored positive non-small cell lung cancer data specifically in patients with a high level of PD-L1 expression.

Bristol-Myers also touted some early-stage Phase I/II data from its dose-ranging trial evaluating Opdivo in previously treated patients with hepatocellular carcinoma, or advanced liver cancer. "Initial findings demonstrated that the estimated survival rate in evaluable patients (n = 47) was 62% at 12 months," according to the biotech.

Merck was first to grab the spotlight at ASCO early Friday when it announced a partnership with Amgen ($AMGN) that will pair the Big Biotech's T-Vec, a likely near-term winner at the FDA, with Keytruda (pembrolizumab) for metastatic squamous cell carcinoma of the head and neck. And later in the day it succeeded in keeping some of the attention on Keytruda with positive data on head and neck cancer.

Among evaluable patients in the early-stage study the overall response rate to Keytruda was 24.8%, a significant improvement over the 19.6% ORR reported last year at ASCO.

"Based on the results observed to date, we are advancing multiple registrational studies in head and neck cancer including randomized evaluations of overall survival and progression-free survival with Keytruda, as monotherapy and in combination with chemotherapy, compared to standard of care," said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories.

等翻译

from google translate

最先进的数据来自一个关键性III期临床百时美'Opdivo（nivolumab），它击败了化疗的非鳞状非小细胞肺癌 - 肺癌的最常见形式。 Opdivo被批准用于晚期非小细胞肺癌鳞癌早在春天布里斯托尔 - 迈尔斯在所有重要的肺癌抓住市场早期的领先默克。

以前治疗的患者在将死-057研究的Opdivo手臂表现出了19.2％的回应率，比多西他赛为12.4％。反应是相当多的耐用Opdivo - 平均17.1个月对5.6个月 - 而中位总生存率nivolumab组打12.2个月比9.4个月，多西他赛组。

调查人员还强调，查明在其肿瘤的高水平的PD-L1的患者亚组特别敏感，中位生存率nivolumab击败17个月相比，9个月的多西紫杉醇治疗。

“这标志着二线治疗肺癌的化疗时代的结束，”百时美'福阿德Namouni告诉路透社记者。

Namouni补充说，百时美将采取它的情况下对药物使用本品，它很可能是期待已久的一个更广泛的认可。该机构很快交出了首次批准肺癌和显示目前丝毫没有减缓的迹象。

但数据并没有全部Opdivo的青睐。西莫·费尔南德斯在今天Leerink写道，他是明显的“失望”的研究0.73的整体风险比，具有明显的好处从患者的肿瘤表达PD-L1水平低倾斜了。那种区分会赞成默克公司和罗氏（$ RHHBY）中的哪一个来了密切两国领导人的背后在现场用生物标志物的方法来打IO。

ISI是Evercore的马克Schoenebaum还指出，相反患者PD-L1水平低的人不太可能从布里斯托尔的药物中获益。这“提出问题，包括是否与病人非鳞状肺癌二号线将设置（而不是简单地只是把Opdivo）要启动PD1或PDL1抗体之前，他们已经肿瘤测试PDL1表达。在这种情况下，如果病人愿意接受活检（其中有一定的危险 - 小，但真正的）可能出现的情况，患者从不同的公司选择诊断检测和抗体，如MRK和罗氏，“Schoenebaum写在纸条给投资者。

几个星期前，罗氏概述积极的二期数据的检查点抑制剂MPDL3280A，具体患者的PD-L1的表达水平高取得了积极的非小细胞肺癌的数据。

百时美还吹捧一些早期的I / II期数据的剂量范围审判以前治疗肝癌患者，或晚期肝癌评估Opdivo。 “初步调查结果显示，在评估的患者（n = 47）的估计存活率为12个月62％，”根据生物技术。

默克公司是第一个抢​​到聚光灯在ASCO周五早时宣布与安进（$ AMGN）建立伙伴关系，将配对大生物技术的T-VEC，一个可能的短期得主在FDA，与Keytruda（pembrolizumab）转移性鳞癌的头部和颈部的癌。并在当天晚些时候它成功地把一些对Keytruda注意对头部和颈部癌症的积极数据。

在评估患者在早期研究中的整体反应速度Keytruda为24.8％，一显著改善在19.6％ORR报道，去年在ASCO。

“根据观察到迄今为止的结果，我们正在推进的头部和颈部癌症，包括总生存率和无进展生存与Keytruda的随机评价多registrational研究，如单药和联合化疗相比，护理标准，”说罗杰博士Dansey，高级副总裁和治疗领域的头，肿瘤后期开发阶段，默克研究实验室。