MPDL3280A: Responses Better in Smokers than in Nonsmokers in Advanced Lung Cancer

Phoebe Starr

October 2013, Vol 4, No 8 - ESMO 2013 Conference


Amsterdam, The Netherlands—For the first time, a therapy for non–small-cell lung cancer (NSCLC) has achieved responses in smokers better than in nonsmokers. The antibody MPDL3280A also achieved good responses in squamous and adenoma histologic types of NSCLC.

These results of a phase 1 study in patients with metastatic NSCLC were so encouraging that experts suggested bypassing phase 2 studies and going on to phase 3 clinical trials directly.

Recruitment for this human monoclonal antibody is ongoing for phase 2 and 3 trials in NSCLC.

“We are at the beginning of a new era. After 30 years of research in immunotherapy for lung cancer, we have one that works, and it works in smokers,” said lead investigator Jean-Charles Soria, MD, PhD, of the Department of Medicine, Institut Gustav Roussy, Villejuif, France. “In this study, smokers responded much better than nonsmokers. This is great news for lung cancer patients—the majority are current or former smokers. The data are preliminary, but the trends are extremely promising,” Dr Soria added.

Study Results
The study results were based on 85 patients (53 evaluable for efficacy) with NSCLC. Patients received an intravenous infusion of MPDL3280A every 3 weeks for a median duration of 106 days (range, 1-450 days). The median duration of therapy was 48 weeks.

Of the 85 patients, 55% were heavily pretreated with at least 3 previous therapies, and 81% were smokers or previous smokers; 19% were never smokers.

MPDL3280A was considered safe. The majority of adverse events were mild. No dose-limiting toxicities were identified in this trial, nor were any grade 3 to 5 adverse events reported.

The objective response rate (ORR) was 21% in the overall population and 23% in patients with NSCLC; 17% of responders were stable over 24 weeks.

The 24-week progression-free survival rate was 44% in squamous-cell NSCLC and 46% in non–squamous-cell NSCLC.

PD-L1 expression (the target of MPDL3280A) was directly correlated with response, with the best response seen in those with the highest expression of PD-L1 on immunohistochemistry (IHC) 3. Those with IHC 3 also had less progressive disease. Although based on very small numbers of patients, the ORR was 46% in patients with PD-L1 IHC 2 and IHC 3, and 86% in those with IHC 3.

Responses were sustained over time in all but 1 patient, Dr Soria said.

Smoking status was a predictor of response; former or current smokers had an ORR of 26% compared with 10% in never smokers.