CHICAGO, IL—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 (NSCLC) who received nivolumab lived, on average, 3.2 months longer than those receiving chemotherapy. Squamous NSCLC accounts for 25% to 30% of all lung malignancies.

Results of the trial, reported in the New England Journal of Medicine (2015: doi:10.1056/NEJMoa150462) and presented at the 2015 American Society for Clinical Oncology (ASCO) Annual Meeting, also showed that after 1 year, the nivolumab group had nearly double the survival rate (42%) of the chemotherapy patients (24%).

“This solidifies immunotherapy as a treatment option in lung cancer,” said Julie Brahmer, MD, director of the Thoracic Oncology Program at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland. “In the 20 years that I’ve been in practice, I consider this a major milestone,” she added, noting that the trial results helped achieve US Food and Drug Administration approval in March to treat such patients whose lung cancer progressed, despite standard chemotherapy.

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Brahmer emphasized 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 said. She suggested that 1- and 2-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, said 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.

For the new trial, hospitals enrolled patients with advanced, squamous non-small cell lung cancer whose disease had progressed despite initial chemotherapy. Researchers randomly selected 135 patients to receive nivolumab (Opdivo) and 137 others to receive the chemotherapy drug docetaxel. Both drugs are administered intravenously.

Median overall survival of patients receiving nivolumab was 9.2 months, compared with 6 months for patients who received docetaxel. At 1 year, 57 patients (42%) taking nivolumab were alive, compared with 33 patients (24%) taking docetaxel. Approximately 27 patients (20%) receiving nivolumab responded to the drug, compared with 12 (8.8%) who received docetaxel. The median disease-progression free survival was 3.5 months with nivolumab and 2.8 months with docetaxel.

The researchers also reported that nivolumab reduced the relative risk of dying from lung cancer by 41% in those who received the immunotherapy drug, compared with those who received docetaxel.

Furthermore, they said the most severe side effects occurred more often in patients receiving docetaxel (55%) than those receiving nivolumab (6.9%). Patients on nivolumab experienced fatigue, decreased appetite, weakness, as well as colon, kidney, or lung inflammation. Those receiving docetaxel experienced hair loss, fatigue, nausea, diarrhea, and low white blood cell counts, which decreases patients’ ability to fight infections.