In a head-to-head clinical trial comparing standard chemotherapy with the immunotherapy drug nivolumab, researchers found that people with squamous-non-small cell lung cancer who received nivolumab lived, on average, 3.2 months longer than those receiving chemotherapy. Squamous non-small cell lung cancer accounts for 25 to 30 percent of all lung malignancies. Results of the trial, reported in the May 31 issue of the New England Journal of Medicine and presented at the American Society for Clinical Oncology 2015 annual meeting, also showed that after a year, the nivolumab group had nearly double the survival rate (42 percent) of the chemotherapy patients (24 percent).

"This solidifies immunotherapy as a treatment option in lung cancer," says Julie Brahmer, M.D., director of the Thoracic Oncology Program at the Johns Hopkins Kimmel Cancer Center. "In the 20 years that I've been in practice, I consider this a major milestone," she adds, noting that the trial results helped achieve U.S. Food and Drug Administration approval in March to treat such patients whose lung cancer progressed, despite standard chemotherapy.

Brahmer emphasizes that the relatively small increase in median survival time with the use of the new immunotherapy drugs may be somewhat misleading in terms of overall impact of the medicines. "Patients who respond to immunotherapy tend to continue their responses for long durations, and these lengthier responses are cut off in calculations of median overall survival," she says. She suggests that one- and two-year survival data may provide more information about the effectiveness of these drugs than overall median survival rates.

Promising results of an earlier, initial, multicenter clinical trial of nivolumab, first reported in 2013 and directed by Brahmer, led to the current phase III trial of 260 patients treated at hospitals across the world.

Nivolumab is one of a group of so-called "checkpoint inhibitors" that work by disrupting a signaling system used by cancers to avoid detection and destruction by immune cells. The system, says Brahmer, provides a kind of "handshake" or connection between receptors on immune cells, called PD-1, and their sister-proteins on tumor cells, called PD-L1. Checkpoint inhibitors block that handshake, which alerts immune cells to cancer cells and target them for destruction.