Early results of a trial testing the safety of a new type of drug that helps the immune system attack cancer cells is showing promising results in lung cancer patients, especially in those who are smokers or former smokers.
The experimental drug, called MPDL3280A (made by Roche), is being tested in patients with non-small cell lung cancer (NSCLC).
Professor Soria, director of the Site de Recherche Intégrée sur le Cancer (SIRIC) Socrate project at the Institut Gustave Roussy in France, presented the latest data from a phase I clinical trial of the drug at the 2013 European Cancer Congress in Amsterdam on Sunday.
“Our results so far demonstrate that the compound is capable of producing striking and durable responses in non-small cell lung cancer patients with metastatic disease who have failed to respond to previous chemotherapy.”
This is good news for patients with lung cancer, particular smokers and former smokers.
Prof. Soria explains that this is the first study to suggest there might be a link between smoking history and response to blocking a pathway that is key to allowing cancer cells to escape detection by the immune system.
For their international trial, he and his colleagues are recruiting patients with metastatic NSCLC who have failed to respond to chemotherapy.
The trial participants receive an intravenous infusion of MPDL3280A once every 3 weeks.
The initial results include efficacy data for 53 NSCLC patients and safety data for 85 NSCLC patients. It shows 26% of smokers responded to treatment, compared with only 10% of never-smokers.
Prof. Soria says:
“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.”
He goes on to say that most of the recent advances in fighting lung cancer have focused mostly on never-smokers or light smokers.
However, he cautions that while the data looks promising, it is only preliminary.
Lung cancer is very difficult to treat, and once it has started to spread (metastasize) to other parts of the body, it is incurable. Most cases of lung cancer are caused by smoking.
Cancer cells are a type of errant cell that is usually targeted and eliminated by the immune system. But some have the ability to exploit one of several mechanisms and evade the immune system.
One way cancer cells do this is by co-opting a signaling pathway called PD-L1. Prof. Soria says this pathway is “instrumental in enabling cancer cells to escape detection by the immune system.”
The drug that Soria and his colleagues are testing is an example of immunotherapy, or finding ways to boost the immune system’s natural ability to fight cancer.
MPDL3280A is an anti-PD-L1 monoclonal antibody that works by blocking the interaction between PD-L1 and the immune system, thereby boosting the patient’s anti-cancer immune response.
Prof. Soria says he and his colleagues had a hunch that because smoking is usually linked with tumors that have more genetic mutations, then perhaps the immune system of such patients might respond more strongly to blocking PD-L1.
“Our results show that this is likely to be the case because more smokers than non-smokers had a partial response to the therapy,” he adds.
However, he also points out that while the best results so far have been seen in smokers and former smokers, it does not mean the drug will not work in never-smokers with NSCLC. “Some of them benefited from this compound as well,” he adds.
Among the patients who responded to the drug, the treatment lasted between 170 and 534 days. Some patients responded within 6 weeks, and the researchers estimate the median average time to first response is 11.9 weeks.
Another important result from the trial is that the researchers found patients whose tumors had higher levels of PD-L1 expression were more likely to respond to treatment than patients with low levels of PD-L1 expression.
This could be a new way to screen for patients most likely to respond to treatment.
Prof. Soria concludes:
“Our results so far demonstrate that the compound is capable of producing striking and durable responses in non-small cell lung cancer patients with metastatic disease who have failed to respond to previous chemotherapy. The study defines a novel approach to identifying the patients most likely to respond to treatment and identifies potential association between smoking and responses to MPDL3280A.”
He says a robust treatment using just this new drug, which appears to have few serious side-effects and requires the patient to receive only one intravenous infusion every 3 weeks, could be available soon.
While the large phase I trial continues, larger phase II and phase III trials of the drug are already underway.