On May 29, 2015 Bristol-Myers Squibb reported that Opdivo (nivolumab) is the first PD-1 inhibitor to demonstrate superior overall survival versus standard of care (docetaxel) in an open-label, randomized Phase III study (CheckMate -057) evaluating previously-treated patients with advanced, non-squamous non-small cell lung cancer (NSCLC) (Press release, Bristol-Myers Squibb, MAY 29, 2015, View Source [SID:1234504895]). Schedule your 30 min Free 1stOncology Demo! A 27% reduction in the risk of progression or death – the primary study endpoint – was reported for Opdivo (n=292) versus docetaxel (n=290) based upon a hazard ratio of 0.73 (96% CI, 0.59-0.89; P = 0.0015). Opdivo was associated with a doubling of overall median survival across the continuum of PD-L1 expression, starting at 1% level of expression, in the trial. The safety profile of Opdivo in CheckMate -057 was favorable versus docetaxel with grade 3–5 treatment-related adverse events reported in 10% of patients who were treated with Opdivo versus 54% in the docetaxel arm.
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These data will be featured today, May 29, during the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) press briefing at 1:00 – 2:00 PM CDT and presented during a clinical science symposium on Saturday, May 30 from 8:51 – 9:03 AM CDT (Late Breaking Abstract #109).
"CheckMate -057 results reported today mark a milestone in the development of new treatment options for lung cancer, as Opdivo is the first PD-1 inhibitor to show a significant improvement in overall survival in a Phase III trial in non-squamous non-small cell lung cancer compared with the current standard of care, docetaxel," said Luis Paz-Ares, MD, Hospital Universitario Doce de Octubre, Madrid, Spain. "Our goal with clinical cancer research is to always look for new options that may improve upon, or in some cases replace, current standard of care. The CheckMate -057 results represent progress toward establishing a new standard of care that may replace docetaxel in PD-L1 expressers."
Lung cancer is the leading cause of cancer deaths globally, resulting in more than 1.5 million deaths each year, according to the World Health Organization. Lung cancer results in more deaths worldwide than colorectal, breast and prostate cancers combined. Non-small cell lung cancer is one of the most common types of the disease and accounts for approximately 85% of cases. Survival rates vary depending on the stage and type of the cancer when it is diagnosed.
"The survival results from this Phase III trial, as well as from CheckMate -017 in squamous NSCLC, validate the Bristol-Myers Squibb development strategy for Opdivo to improve survival expectations for patients with lung cancer," said Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb. "The CheckMate -057 results defined the role for PD-L1 expression, based upon an overall survival endpoint and showed that patients whose tumor expressed PD-L1 at 1% or greater levels achieved a doubling of overall survival. This represents a significant scientific advance in non-small cell lung cancer."
About CheckMate -057
CheckMate -057 is a landmark Phase III, open-label, randomized clinical trial that evaluated patients with advanced non-squamous NSCLC who had progressed during or after one prior platinum doublet-based chemotherapy regimen. The trial included patients regardless of their PD-L1 status. Secondary endpoints included objective response rate, progression-free survival and efficacy by tumor PD-L1 expression. Patients enrolled in the trial were administered Opdivo 3 mg/kg every two weeks versus standard of care, docetaxel, at 75 mg/m2 every three weeks.
In addition to improving overall survival, Opdivo demonstrated a superior objective response rate of 19% versus 12% for docetaxel (P = 0.0246). The median duration of response for Opdivo was 17.2 months versus 5.6 months for docetaxel, and median time to response of 2.1 months vs. 2.6 months, respectively.
CheckMate -057 also evaluated the efficacy of Opdivo by tumor PD-L1 expression. Of randomized patients, 78% (455/582) had tumor samples allowing the assessment of PD-L1 expression. Rates of PD-L1 expressing tumors were balanced between groups. Across pre-specified 1%, 5%, and 10% expression levels, PD-L1 status was predictive for benefit from Opdivo. In patients with PD-L1 expressing tumors, Opdivo demonstrated improved efficacy across all endpoints at all expression levels.
The safety profile of Opdivo in CheckMate -057 was consistent with prior studies and favorable versus docetaxel. Safety profile also was similar across expressers and non-expressers. Treatment-related adverse events were low in severity with Opdivo and occurred less frequently (any grade: 69%; grade 3–4: 10%) than docetaxel (any grade: 88%; grade 3–4: 54%), including both hematologic and non-hematologic toxicities. Treatment-related serious adverse events were reported less frequently with Opdivo (any grade: 7.3%; grade 3–4: 5.2%) than docetaxel (any grade: 20%; grade 3–4: 18%). Discontinuation due to treatment–related adverse events was less frequent with Opdivo (5%) than docetaxel (15%).
Proven Efficacy Across Histologies in Lung Cancer
CheckMate -057 is the second positive Phase III trial to demonstrate superior overall survival for Opdivo in non-small cell lung cancer. Earlier this year, the Phase III CheckMate -017 trial was stopped early due to superior overall survival versus docetaxel in previously-treated advanced squamous non-small cell lung cancer and formed the basis of the company’s first indication in lung cancer from the U.S. Food & Drug Administration’s (FDA) approval for Opdivo. Trial results from CheckMate -017 will be presented at ASCO (Free ASCO Whitepaper) during an oral abstract session on Sunday, May 31 from 4:30 – 4:42 PM CDT (Abstract #8009).