By David Douglas
NEW YORK (Reuters Health) - 2/8/2019
Treatment with nivolumab (Opdivo, Bristol-Myers Squibb) is associated with improved long-term survival in certain heavily pretreated cancer patients, according to a secondary analysis of a clinical trial.
"This new study provides much-needed data on long-term clinical outcomes associated with nivolumab, a drug that blocks the inhibitory PD-1 receptor on immune cells and reactivates the body's own immune system to fight cancer," Dr. Suzanne L. Topalian of Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, in Baltimore, Maryland, told Reuters Health by email.
In 2006, nivolumab became the first PD-1 blocker to enter clinical testing, but data on long-term outcomes with the drug are limited, Dr. Topalian and colleagues observe in JAMA Oncology, online July 25.
The researchers examined outcomes of 270 patients who were enrolled in a phase 1 clinical trial of nivolumab between 2008 and 2012; 107 had advanced melanoma, 34 had renal-cell carcinoma (RCC) and 129 had non-small cell lung cancer.
Overall estimated five-year survival rates were 34.2% among melanoma patients, 27.7% in RCC patients and 15.6% in lung-cancer patients. Multivariable analysis showed that liver and bone metastases were independently associated with reduced survival (odds ratio, 0.31 for both).
An Eastern Cooperative Oncology Group performance status of zero was independently associated with increased five-year survival (OR, 2.74).
Having treatment-related adverse events of any grade was also tied to significantly increased survival (by a median of 19.8 months). In particular, survival was increased by a median of 20.3 months in those with AEs of grade 3 or more compared to 5.8 months in those with no AEs.
Survival in these patients "exceeded expectations from other kinds of cancer therapies that were available when this study began in 2008," said Dr. Topalian.
"Based on the findings in this study," she added, "we can reassure our patients that if they develop side effects from nivolumab . . . it may very well put them in a better response and long-term-effect category."
Dr. Solange Peters, who wrote an accompanying editorial, told Reuters Health by email, "A comparison with all historical trials strongly highlights the magnitude of the survival gain, with an inexorable modification of the shape of survival curves, as well as the durability of immunotherapy treatment effect."
"Challenges for the future remain to define the optimal duration of such treatments for each tumor type or patient subgroups, as well as building a stronger biomarker portfolio, allowing refined selection of patients benefiting from this strategy," added Dr. Peters, of Centre Hospitalier Universitaire Vaudois, in Lausanne, Switzerland.
The study was sponsored by Bristol-Myers Squibb. Dr. Topalian and other authors have relationships with the company and a number are employees.
JAMA Oncol 2019.