For the first time, a therapy for non-small cell lung cancer (NSCLC) has achieved more responses in smokers than nonsmokers. The antibody MPDL3280A also achieved good responses in the squamous and adenoma histologic types of NSCLC.
These phase 1 study results in patients with metastatic NSCLC were so encouraging that experts suggested bypassing phase 2 and going directly to phase 3 studies.
Genentech’s development program for the monoclonal antibody includes ongoing recruitment 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 author Jean-Charles Soria, MD, Institut Gustave Roussy, Paris, France, at the European Cancer Congress (ESMO/ECCO/ESTRO), held September 27-October 1, 2013, in Amsterdam, the Netherlands. “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,” Soria added.
The study results were based on 85 patients (53 evaluable for efficacy) who received treatment with an intravenous infusion of MPDL3280A every 3 weeks for a median duration of 106 days (range, 1-450 days). Median duration of therapy was 48 weeks.
Of the 85 patients with NSCLC, 55% were heavily pretreated with 3 or more previous therapies and the majority were smokers or ex-smokers (81%); 19% never smoked.
MPDL3280A was considered safe. Most adverse events were mild. No dose-limiting toxicities were identified in this trial, nor was any grade 3 to 5 pneumonitis or diarrhea reported. Grade 3 and 4 adverse events were reported in 34%, but these were not necessarily treatment related, as some were cancer related (ie, dyspnea, fatigue).
Objective response rate (ORR) was 24% 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 nonsquamous 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, 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 patients except one, Soria said.
Smoking status was a predictor of response; former/current smokers had an ORR of 26% (n = 43) compared with 10% in never-smokers (n = 10).
Reference
Soria JC, Cruz C, Bahleda R, et al. Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC): additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PDL1). Presented at: 2013 European Cancer Congress; September 27-October 1, 2013; Amsterdam, the Netherlands. Abstract 3408.
