PHILADELPHIA (September 27, 2015) – Effective treatment options are limited for patients with nonsquamous non–small-cell lung cancer whose disease has progressed after initial treatment with platinum-based chemotherapy. A phase-3, randomized, open-label international clinical trial showed significantly longer median overall survival with nivolumab (Bristol-Myers Squibb) immunotherapy than with docetaxel (Sanofi-Aventis) for these patients. The trial results were presented at The European Cancer Congress 2015 and published online in the New England Journal of Medicine.
“This introduces a new paradigm in lung cancer treatment—immunotherapy—and gives our patients another option for treatment,” says Hossein Borghaei, DO, chief of Thoracic Medical Oncology at Fox Chase Cancer Center – Temple Health and lead investigator of the CheckMate 057 study. “Once nivolumab is approved in the nonsquamous histology, physicians can use this drug for management of their patients when there is progression after standard chemotherapy.”
Lung cancer is the most common cancer worldwide, according to the World Cancer Research Fund International, and about 85% to 90% is non–small-cell lung cancer (NSCLC).
The CheckMate 057 trial, funded by Bristol-Myers Squibb, showed a median overall survival of 12.2 months with nivolumab and 9.4 months with docetaxel, or a 27% lower risk of death with nivolumab. The overall survival rate at one year was 51% among the 292 patients treated with nivolumab compared with a 39% rate among the 290 patients treated with docetaxel. At 18 months, overall survival was 39% with nivolumab and 23% with docetaxel.
Most patients included in the trial had stage IV nonsquamous NSCLC, were current or former smokers, and their median age was 62 years.
For a subgroup of patients, those whose tumors expressed PD-L1, or programmed death ligand 1, nivolumab resulted in longer overall and progression-free survival and higher objective response rates than docetaxel. There was no difference, however, in overall survival between nivolumab and docetaxel among patients whose tumors did not express PD-L1. Nivolumab is a human monoclonal antibody that is designed to block the interaction between PD-1 and its ligand PD-L1. Blocking this PD-1 activity can decrease tumor growth.
Although the frequencies of adverse events were similar for the two treatments, there were fewer grade 3 or 4 adverse events among patients treated with nivolumab. Ten percent of patients treated with nivolumab had a grade 3 or 4 adverse event compared with 54% of patients treated with docetaxel. In the NEJM publication, Borghaei and his colleagues note that the improved safety profile and the durability of the responses to nivolumab suggest it may be a reasonable option for patients, regardless of their PD-L1 expression.
Borghaei says that the current PD-L1 biomarker “appears to be inadequate,” and that better definition is needed of the patients who would benefit the most from immunotherapy. “Future research should concentrate on defining this population. We also need to assess the effectiveness of immunotherapy in the front-line setting, at the time of initial diagnosis,” he says. “Some studies looking into this question have already been completed, and we are awaiting the results.”
Nivolumab is approved for treatment of metastatic melanoma and for metastatic squamous NSCLC that has progressed on or after platinum-based chemotherapy. Docetaxel is approved as second-line treatment for advanced NSCLC.