Based on the results of two large international randomized trials, the FDA approved the anti–PD-L1 agent atezolizumab in October. It is the first PD-L1 inhibitor approved for use in patients with metastatic non–small cell lung cancer that has advanced in spite of treatment with platinum-based chemotherapy.

Already sanctioned by the FDA in May for urothelial carcinoma, the anti–PD-L1 agent atezolizumab (Tecentriq; Genentech) earned approval in late October for use in patients with metastatic non–small cell lung cancer (NSCLC) that has advanced in spite of first-line treatment with platinum-based chemotherapy. For patients with EGFR or ALK aberrations, the drug is indicated for use after the disease has progressed with an FDA-approved targeted therapy.

Atezolizumab's approval was based on the results of two large international randomized trials: the phase III OAK and phase II POPLAR studies. In the OAK study, in which researchers conducted a primary analysis of the first 850 of 1,225 patients, those who received atezolizumab had a median overall survival (OS) of 13.8 months, compared with 9.6 months for those treated with docetaxel. In the POPLAR study, median OS was 12.6 months and 9.7 months, respectively. Patients with both squamous and non-squamous disease were enrolled, regardless of their PD-L1 status.

The FDA has greenlighted two other immunotherapies for use in patients with NSCLC in the same clinical setting: the anti–PD-1 antibodies pembrolizumab (Keytruda; Merck) and nivolumab (Opdivo; Bristol-Myers Squibb). Pembrolizumab can be used as a second-line therapy in patients with NSCLC that expresses PD-L1, as determined by a companion diagnostic test, and that has spread after treatment with platinum-based chemotherapy, as well as in patients with EGFR or ALK aberrations whose disease has progressed on a targeted, FDA-approved therapy. Nivolumab is also approved as a second-line therapy for NSCLC, but tumors need not be positive for PD-L1.

With three immunotherapies now approved for NSCLC, “the challenge is figuring out whether there truly is a difference” among them, says Pasi A. Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Center in Boston, MA. “For example, it would be wonderful to have a biomarker to tell me that a patient is not going to respond to nivolumab but they're going to respond to atezolizumab, or vice versa; that would be important information to have, but we don't have that today.”

However, rather than conduct head-to-head trials of individual PD-1 and PD-L1 inhibitors, Jänne posits that resources might be better spent studying the drugs as first-line treatments, as well as how to improve their efficacy, perhaps by combining them with standard chemotherapy. “Of course there's also a lot of excitement and enthusiasm about the anti–CTLA-4/anti–PD-1 combination, something that's approved in melanoma and has activity in lung cancer, to see if that combination is better than chemotherapy,” says Jänne. Data from some such combination trials should be released next year.

Tyler Curiel, MD, MPH, a cancer immunology researcher at The University of Texas Health Science Center in San Antonio, agrees that more studies of immunotherapy combinations need to be completed because they may better hinder tumors' ability to mutate and evolve than single agents—and because they have benefited patients with a variety of malignancies. “These are not lung cancer drugs, not skin cancer drugs,” he says. “They are cancer drugs.” –Suzanne Rose