Smokers respond well to new antibody drug for NSCLC

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An antibody that helps the immune system to recognize and attack cancer cells has had particularly encouraging responses in patients who are smokers or former smokers, according to a newly reported trial. The data from 85 patients with non-small cell lung cancer (NSCLC) in a large, phase I clinical trial of MPDL3280A was presented at the 2013 European Cancer Congress (ECC) in Amsterdam, The Netherlands.

"This is the first study to suggest a potential relationship between smoking history and response to inhibiting the PD-L1/PD-1 pathway—a pathway that is instrumental in enabling cancer cells to escape detection by the immune system. In this study, 26% of smokers responded to treatment, whereas only 10% of never-smokers responded. The fact that smokers seemed to respond better is great news for lung cancer patients, because the majority of them are former or current smokers. Most advances in lung cancer over the last 5 years have mainly focused in never or light smokers," said Professor Jean-Charles Soria, who is Director of the Site de Recherche Intégrée sur le Cancer (SIRIC) Socrate project at the Institut Gustave Roussy, France.

Lung cancer, which is usually caused by smoking, is extremely difficult to treat successfully, and it is incurable once it has started to metastasize to other parts of the body. The programmed death 1 protein PD-1 and its signalling molecule PD-L1 prevent the body's immune system from attacking and killing cancer cells, which allows the cancer to spread. However, the anti-PD-L1 monoclonal antibody, MPDL3280A, works by blocking the interaction between PD-L1 and the immune system, thereby boosting a patient's anticancer immune response.

This international trial is enrolling patients with metastatic non-small cell lung cancer (NSCLC) who have failed to respond to chemotherapy. The enrolled patients are treated with an intravenous infusion of MPDL3280A once every 3 weeks. At the ECC2013 Congress, efficacy data was presented for 53 NSCLC patients and safety data for 85 NSCLC patients—the largest group of patients to be treated with anti-PD-L1 blockade to date.

"We hypothesized that smoking was associated with tumors that harbor more genetic mutations and, therefore, the immune systems of these patients might be more likely to respond and attack the tumors once PD-L1 had been blocked," explained Soria. "Our results show that this is likely to be the case because more smokers than nonsmokers had a partial response to the therapy." Soria added that some nonsmokers also responded to the anti-PD-L1 antibody.

Among the responding patients, treatment duration ranged from 170 to 534 days. Responses were rapid and sustained, with patients responding to the drug within 6 weeks. The median average time to first response was 11.9 weeks. Soria concluded, "Our results so far demonstrate that the compound is capable of producing striking and durable responses in NSCLC patients with metastatic disease who have failed to respond to previous chemotherapy."

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