Squamous NSCLC Improves with Atezolizumab Plus Chemo

The PD-L1 inhibitor atezolizumab (Tecentriq; Genentech) in combination with chemotherapy may be a more effective first-line treatment than chemotherapy alone for patients with advanced squamous non–small cell lung cancer (NSCLC), according to data presented on June 2 at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL. In a phase III clinical trial, patients who received the combination had longer progression-free survival (PFS), a higher objective response rate (ORR), and a longer duration of response (DOR) than patients who received chemotherapy, regardless of PD-L1 expression levels.

Atezolizumab is FDA-approved to treat patients with metastatic NSCLC whose disease has progressed following first-line chemotherapy, the current standard of care. However, “squamous non–small cell lung cancer remains a very difficult-to-treat disease, and there have been very limited new treatment options in the last few decades,” said Robert Jotte, MD, PhD, of Rocky Mountain Cancer Centers in Denver, CO, who presented the results. He added that patients with the disease have historically had poor outcomes when treated with first-line chemotherapy, which was the motivation for the IMpower131 trial.

Researchers reported interim results from 683 patients with stage IV squamous NSCLC who received either atezolizumab plus a chemotherapy regimen of carboplatin and nab-paclitaxel (Abraxane; Celgene) or just the chemotherapy regimen. They found that patients treated with the immunotherapy–chemotherapy combination had a 12-month PFS rate of 24.7%, compared with 12% in patients who received chemotherapy alone. Prolonged PFS was seen regardless of PD-L1 level, but was the largest in patients with high expression, or at least 50%—10.1 months versus 5.5 months with chemotherapy.

Patients who received the combination also had increases in ORR and median DOR, regardless of PD-L1 level, with an ORR of 49% and a DOR of 7.2 months, compared with an ORR of 41% and a DOR of 5.2 months in patients who received chemotherapy. The benefit was most pronounced in patients with high PD-L1 expression: Those treated with the combination had an ORR of 60% and DOR of 18.7 months, compared with 33% and 5.3 months for chemotherapy alone. There was no difference in overall survival (OS) between the combination and chemotherapy groups.

Atezolizumab plus chemotherapy may benefit patients with metastatic nonsquamous NSCLC as well, according to results from the phase III IMpower150 trial, which was also presented at the ASCO meeting and concurrently published in The New England Journal of Medicine. In this trial, patients who received the combination had a median PFS of 8.3 months and a median OS of 19.2 months, compared with 6.8 months and 14.7 months in patients who received chemotherapy alone. Again, all patients benefited, regardless of their PD-L1 expression level.

“We previously thought that you needed a high level of PD-L1 expression to get the best result from immunotherapy,” said David Graham, MD, of the Levine Cancer Institute in Charlotte, NC, commenting on IMpower131. “The results of this trial, the largest randomized trial to date in this population, show that that is indeed not the case. The benefit of immunotherapy was seen across all groups.”

Graham added that although there was no difference in OS between the study arms in the interim analysis, that could change as the trial continues. “If and when that's known, I think we'll clearly have a new standard of care for the front-line treatment of squamous cell non–small cell lung cancer,” he said. –Catherine Caruso