Adding pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nanoparticle albumin-bound (nab)–paclitaxel may significantly prolong overall survival (OS) and progression-free survival (PFS) compared with chemotherapy alone in patients with previously untreated metastatic squamous non–small-cell lung cancer (NSCLC). The study, published in The New England Journal of Medicine, also found that this combination does not significantly increase toxicity.

Luis Paz-Ares, MD, of the Hospital Universitario, Spanish National Cancer Research Center, Universidad Complutense and Ciberonc in Madrid, Spain, and colleagues conducted a double-blind, phase III trial evaluating 559 patients with untreated metastatic squamous NSCLC (ClinicalTrials.gov number, NCT02775435). All patients were randomly assigned 1:1 to treatment with either 200 mg of pembrolizumab or saline placebo for up to 35 cycles; they also received carboplatin and either paclitaxel or nab-paclitaxel for the first 4 cycles. The primary end-points were OS and PFS.

The researchers found that the median OS was 15.9 months in the pembrolizumab-combination group compared with 11.3 months in the placebo-combination group (hazard ratio [HR] for death, 0.64), with a median follow-up of 7.8 months. The OS benefit remained regardless of the level of programmed death ligand 1 (PD-L1) expression. Median PFS rates were similar: the PFS rate was 6.4 months in the pembrolizumab-combination group vs 4.8 months in the placebo-combination group (HR for disease progression or death, 0.56).

“The addition of pembrolizumab to chemotherapy improves outcomes, including overall survival, of treatment-naÃ¯ve patients with advanced squamous cell of the lung, irrespective of PD-L1 status, at the cost of affordable toxicity. It represents a new standard of care in this setting,” said Paz-Ares.

Of note, researchers also found that the addition of pembrolizumab did not significantly increase toxicity. Adverse events of grade 3 or higher were reported in 69.8% of patients in the pembrolizumab-combination group compared with 68.2% of patients in the placebo-combination group. However, the discontinuation rate due to adverse events was much higher in the pembrolizumab-combination group than in the placebo-combination group (13.3% vs 6.4%, respectively). “The observed side effects were those expected from the addition of the two treatment strategies. Side effects are pretty much manageable, and no unexpected signals were identified,” Paz-Ares told Cancer Network.

David E. Gerber, MD, a professor of Internal Medicine and Clinical Sciences at the University of Texas Southwestern Medical Center in Dallas, said this important study represents yet another example of how immunotherapy has brought the first major advances to squamous cell lung cancer in decades.

“Almost all of the other recent, promising developments in medical lung cancer therapy have been limited to non-squamous cases, including molecularly targeted therapies, some antiantiogenic therapies targeting tumor blood vessel growth, and newer chemotherapy agents such as pemetrexed,” Gerber told Cancer Network.