More Benefits for Checkpoint Inhibitors in NSCLC

At the European Cancer Congress (ECC), held last month in Vienna, Austria, three groups of researchers presented new evidence that checkpoint inhibitors are effective for certain patients with non–small cell lung cancer (NSCLC).

Earlier this year, nivolumab (Opdivo; Bristol-Myers Squibb) and pembrolizumab (Keytruda; Merck), already approved for melanoma, became the first checkpoint inhibitors to receive FDA approval as second-line therapies for NSCLC. Tumors protect themselves from immune attacks by producing the protein PD-L1, which interacts with the PD-1 receptor on T cells and shuts them down. Nivolumab and pembrolizumab counteract this defense by targeting PD-1.

One study presented at the ECC and reported in The New England Journal of Medicine led to the approval of nivolumab for the 70% of patients with NSCLC who have non-squamous tumors. (Initially, the drug received FDA approval for patients with squamous tumors.) In this phase III trial, Hossein Borghaei, DO, of the Fox Chase Cancer in Philadelphia, PA, and colleagues assigned 582 patients who had previously received platinum-based chemotherapy to receive either nivolumab or docetaxel. Overall survival (OS) for the nivolumab group was 12.2 months, versus 9.4 months for the docetaxel group. The results suggest that nivolumab “is a new potential option for patients who can't usually get targeted therapies,” such as erlotinib (Tarceva; Genentech/Astellas), that work against tumors with particular mutations, says Borghaei.

Two additional studies reported at the ECC showed positive results for another checkpoint inhibitor, atezolizumab (MPDL3280A; Roche/Genentech), which blocks PD-L1. In the single-arm, phase II BIRCH study, Benjamin Besse, MD, PhD, of Gustave Roussy in Villejuif, France, and colleagues gave atezolizumab to 667 patients with advanced NSCLC and high levels of PD-L1. The objective response rate was 19% when atezolizumab was a first-line therapy and 17% when it was a second-line or subsequent therapy. Besse notes that the drug seemed to work best in patients with the highest levels of PD-L1.

The second study of atezolizumab, the phase II POPLAR trial, involved 287 patients with NSCLC who had already received chemotherapy. Johan Vansteenkiste, MD, PhD, of University Hospitals KU Leuven in Belgium, and colleagues treated the patients with either atezolizumab or the chemotherapy drug docetaxel, a standard second-line treatment for NSCLC. OS was 12.6 months in patients who received atezolizumab, compared with 9.7 months in those who received docetaxel. As in the BIRCH study, atezolizumab appeared to be most effective in patients with the highest levels of PD-L1.

For treating NSCLC, checkpoint inhibitors “are quickly becoming the standard for the second line, and we will see about the first line,” notes Aaron Mansfield, MD, of the Mayo Clinic in Rochester, MN, who wasn't connected to any of the studies. However, he cautions, questions remain about which patients should receive the treatments and how to select them. “PD-L1 is not perfect for predicting who will respond” to the drugs, he says.