Immunotherapy better than chemo for survival of patients with non-squamous non-small-cell lung cancer

Immunotherapy with nivolumab showed significantly longer median overall survival than second-line chemotherapy in patients whose non-squamous non-small-cell lung cancer (NSCLC) continued to progress after first-line chemotherapy, according to findings from a phase 3 international clinical trial.

“This introduces a new paradigm in lung cancer treatment—immunotherapy—and gives our patients another option for treatment,” said the study’s lead investigator Hossein Borghaei, DO, chief of Thoracic Medical Oncology at Fox Chase Cancer Center–Temple Health, in Philadelphia, PA.

The findings from this study—the CheckMate 057 trial—were simultaneously presented September 28, 2015 at The European Cancer Congress 2015 in Vienna, Austria, and published online in the New England Journal of Medicine.

Currently, nivolumab is FDA approved for the treatment of metastatic squamous NSCLC with progression on or after platinum-based chemotherapy. It is marketed as Opdivo® by Bristol-Myers Squibb.

Patients with non-squamous NSCLC have limited treatment options and a dismal prognosis after their disease has progressed and initial treatment with platinum-based chemotherapy has failed. “Once nivolumab is approved in the non-squamous histology, physicians can use this drug for management of their patients when there is progression after standard chemotherapy,” Dr. Borghaei said.

In this international clinical trial of 582 patients with non-squamous NSCLC, investigators randomized 292 to receive treatment with nivolumab at a dose of 3 mg/kg administered intravenously every 2 weeks while 290 patients received docetaxel at a dose of 75 mg/m² intravenously every 3 weeks. Most patients (median age 62 years) had stage IV non-squamous NSCLC, and were current or former smokers. The trial’s primary endpoint was overall survival. Treatment continued until the cancer progressed or patients discontinued due to toxic side effects. The trial was funded by Bristol-Myers Squibb.

Results showed a median overall survival of 12.2 months among patients treated with nivolumab and 9.4 months among patients treated with docetaxel—a 27% lower risk of death with nivolumab. The overall survival rate at 1 year was 51% with nivolumab compared with 39% with docetaxel. At 18 months, overall survival was 39% with nivolumab and 23% with docetaxel.

Frequency of adverse events was similar for the two treatments, but nivolumab resulted in fewer significant adverse events—10% of patients treated with nivolumab had a grade 3 or 4 adverse event compared with 54% of patients treated with docetaxel.

“This clinical trial shows that people with lung cancer not only live longer when treated with the immunotherapy drug nivolumab, but their quality of life is better and toxicities are fewer and less severe,” said contributing author David Gerber, MD, associate professor of Internal Medicine and co-director of the Experimental Therapeutics Program at the University of Texas Southwestern Medical Center, in Dallas, Texas.

In addition to studying efficacy and safety, the trial examined the protein biomarker PD-L1 (programmed death ligand 1), which is believed to play a role in suppressing the immune system.

Nivolumab blocks the interaction between PD-1 and its ligand PD-L1, which can decrease tumor growth. The study results indicated that patients whose tumors expressed PD-1 experienced the greatest benefit from nivolumab, resulting in longer overall and progression-free survival and higher objective response rates than docetaxel. There was no difference in overall survival between nivolumab and docetaxel among patients whose tumors did not express PD-L1.

The current PD-L1 biomarker “appears to be inadequate,” and better definition is needed of the patients who would benefit the most from immunotherapy, Dr. Borghaei said.

“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 added. “Some studies looking into this question have already been completed, and we are awaiting the results.”

For more information on lung cancer, go to the Lung Cancer Resource Center.