NEW IMMUNOTHERAPY OPDIVO™ (NIVOLUMAB) FIRST PD-1 INHIBITOR TO DEMONSTRATE SUPERIOR OVERALL SURVIVAL VERSUS STANDARD OF CARE (DOCETAXEL) IN PREVIOUSLY TREATED NON-SQUAMOUS NON-SMALL CELL LUNG CANCER IN PIVOTAL PHASE 3 TRIAL
Opdivo decreased risk of progression or death by 27% compared to standard of care in second positive Phase 3 trial in previously treated patients
A new Bristol-Myers Squibb immunotherapy, Opdivo™ (nivolumab), is the first PD-1 inhibitor to demonstrate superior overall survival versus standard of care (docetaxel) in previously-treated patients with advanced, non-squamous non-small cell lung cancer (NSCLC). Results from the open-label, randomized Phase 3 study were presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
In the study, CheckMate-057, 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 favourable 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.
“These study results are significant because they demonstrate positive impact on both survival and progression of disease in non-squamous non-small cell lung cancer. This is the first PD-1 inhibitor to demonstrate these results, giving it the potential to become an important new treatment option,” said Dr. Glenwood Goss, professor of medicine and director of Clinical and Translational Research at the Ottawa Hospital Cancer Centre at the University of Ottawa. “This is a cancer that is very much in need of new therapies and different options because of the treatment gap that currently exists. We are very excited with what we are seeing with this data.”
Lung cancer is the leading cause of cancer deaths globally and in Canada, where it kills more than twice as many patients as breast, prostate and colorectal cancer combined.[i]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. Despite treatment advances, the five-year survival rate for lung cancer in Canada is among the lowest for all cancers at just 17%.[ii]
“The reality is that lung cancer survival lags behind other major cancers. There is such a vast and critical unmet need that must be addressed in order to deal with this deadliest of cancers,” said Shem Singh, Executive Director of Lung Cancer Canada. “Research in this area is vital because of the potential impact it has on survival. Promising new research brings hope to patients and their families who may currently find themselves with few options. This announcement is tremendous news for the lung cancer community.”
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 favourable versus docetaxel. Safety profile also was similar across expressers and non-expressers (<1%). 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%).
The safety and efficacy of Opdivo for non-small cell lung cancer is still under investigation in Canada.
Lung cancer in Canada
More than one in every 12 Canadians will get lung cancer. It is the most common cancer among those that affect both men and women,[iii] with more than 26,000 cases diagnosed in 2014.[iv] Lung cancer is by far the leading cause of cancer deaths in Canada, in both men and women. It caused 20,500 deaths in 2014 – 27% of all cancer deaths.[v] A Canadian dies of lung cancer every 27 minutes. Despite treatment advances, the five-year survival rate for lung cancer in Canada is among the lowest for all cancers at just 17%, higher only than the rates for cancer of the esophagus (14%) and pancreas (8%).[vi] Rates of lung cancer vary between men and women and different regions of Canada, being highest in Quebec and lowest in British Columbia.[vii] While smoking is the leading cause of lung cancer, half of patients are not smoking at the time of diagnosis: 15% are lifelong non-smokers and 35% more are ex-smokers, many who quit years before.[viii]
Immuno-oncology at Bristol-Myers Squibb
Surgery, radiation, cytotoxic or targeted therapies have represented the mainstay of cancer treatment over the last several decades, but long-term survival and a positive quality of life have remained elusive for many patients with advanced disease. To address this unmet medical need, Bristol-Myers Squibb is leading research in an innovative field of cancer research and treatment known as immuno-oncology, which involves agents whose primary mechanism is to work directly with the body’s immune system to fight cancer. The company is exploring a variety of compounds and immunotherapeutic approaches for patients with different types of cancer, including researching the potential of combining immuno-oncology agents that target different pathways in the treatment of cancer. Bristol-Myers Squibb is committed to advancing the science of immuno-oncology, with the goal of changing survival expectations and the way patients live with cancer.
About Bristol-Myers Squibb Canada
Bristol-Myers Squibb Canada is an indirect wholly-owned subsidiary of Bristol-Myers Squibb Company, a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb global operations, visit www.bms.com. Bristol-Myers Squibb Canada has been delivering innovative medicines for serious diseases to Canadian patients in the areas of cardiovascular health, oncology, neuroscience, immunoscience and virology for over 80 years. Bristol-Myers Squibb Canada employs over 300 people across the country. For more information, please visit www.bmscanada.ca.
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[i]Canadian Cancer Society, Canadian Cancer Statistics, Estimated deaths and age-standardized mortality rates (ASMR) for cancers by sex, Canada, 2014, p. 45.
[ii]Canadian Cancer Society, Canadian Cancer Statistics, Five-year relative and observed survival for selected cancers by sex, ages 15–99 years at diagnosis, Canada (excluding Quebec*), 2006–2008, p. 64.
[iii]Canadian Cancer Society, Canadian Cancer Statistics, Lifetime probability of developing cancer overall and by age group, Canada, 2009, p. 23.
[iv]Canadian Cancer Society, Canadian Cancer Statistics, Estimated new cases and age-standardized incidence rates (ASIR) for cancers by sex, Canada, 2014, p. 24.
[v]Canadian Cancer Society, Canadian Cancer Statistics, Estimated deaths and age-standardized mortality rates (ASMR) for cancers by sex, Canada, 2014, p. 45.
[vi]Canadian Cancer Society, Canadian Cancer Statistics, Five-year relative and observed survival for selected cancers by sex, ages 15–99 years at diagnosis, Canada (excluding Quebec*), 2006–2008, p. 64.
[vii]Canadian Cancer Society, Canadian Cancer Statistics, Estimated age-standardized incidence rates (ASIR) for selected cancers by sex and province, Canada, 2014, p. 36.
[viii]Lung Cancer Canada, The Faces of Lung Cancer: Fighting Disparity, p. 4, accessed at: http://www.lungcancercanada.ca/resources/site1/general/Reports%20and%20Media%20Releases/Faces%20of%20Lung%20Cancer%20Report.pdf