A new era of lung cancer therapy is close to dawning, using drugs that can prevent tumor cells from evading the immune system, experts said at the Fourth European Lung Cancer Congress (ELCC) in Geneva, Switzerland.
For decades, scientists and doctors thought immunotherapy, which uses treatments that harness the immune system to fight a disease, was of marginal benefit in lung cancer, said Jean-Charles Soria, MD, PhD, Institute Gustave Roussy in Paris, France.
However, Soria explained that a new class of drugs, known as “immunocheckpoint regulators,” has shown huge potential. New data on several of these drugs were presented at the conference.
Two of the most interesting immunocheckpoint molecules in this setting are known as PD-1 (programmed death) and PD-L1 (programmed death ligand-1). When these molecules interact in tumors, they prevent immune cells from attacking the cancer cells, allowing them to escape and multiply.
“Blocking PD-1 and PD-L1 can result in striking and durable responses, with global overall response rates of 20% to 25% as monotherapy in metastatic non-small-cell lung cancer,” Soria says. “These impressive results have yet to be confirmed in other trials; nonetheless immune checkpoint inhibitors will most likely become part of daily practice for non-small-cell lung cancer in the near future. Immunotherapy has come of age and is here to stay.”
At ELCC, Armida D’Incecco, MD, from Istituto Toscano Tumori in Livorno, Italy, and colleagues, suggested that combining immunotherapy drugs with other targeted therapies in lung cancer is likely to be beneficial.
D’Incecco’s group studied the expression of PD-L1 and PD-1 in a group of 123 non-small cell lung cancer patients. They also analyzed the patients’ cancers for mutations in two other molecules: EGFR, which is the target of existing drugs gefitinib and erlotinib, and KRAS.
They found that the tumors that expressed PD-L1 also tended to carry EGFR mutations. Further, PD-1 expression in the tissue sample was associated with KRAS-mutated status.
Among patients whose tumors carried EGFR mutations, and who were treated with targeted therapies, those whose tumors were also positive for PD-L1 took longer to progress, and tended toward longer overall survival than PD-L1 negative patients.
These results suggest a strong correlation between PD-L1 expression and EGFR mutation and between PD-1 expression and KRAS mutations, supporting further investigation of anti-PD-L1 or anti-PD-1 agents in combination with targeted therapies.
Soria noted, “This study suggests that PD-L1 expression is correlated with EGFR mutation. If this is true, then immunocheckpoint blockade combination with EGFR tyrosine kinase inhibitors is a major path towards improving outcome of patients who have EGFR-mutant non-small cell lung cancer.” He added that trials to explore this relationship are underway.