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Immunotherapy Data Herald New Era of Lung Cancer Treatment

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Key Points

  • Immune checkpoint inhibitors are showing great potential in the treatment of lung cancer.
  • Results of one study have suggested a strong correlation between PD-L1 expression and EGFR mutations and between PD-1 expression and KRAS mutations.

A new era of lung cancer therapy is dawning, using drugs that can prevent tumor cells from evading the immune system, experts reported at the 4th European Lung Cancer Congress. For decades, scientists and doctors thought immunotherapy was of marginal benefit in lung cancer, said ESMO spokesperson Jean-Charles Soria, MD, PhD, of Institut Gustave Roussy, Paris. However a new class of drugs known as immune checkpoint regulators have shown huge potential, he said. New data on several of these drugs will be presented at the conference, held March 26 to 29 in Geneva, Switzerland.

Two immune checkpoint molecules of particular interest in this setting are the programmed death 1 (PD-1) receptor and its ligand PD-L1. 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,” Dr. Soria said. “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.”

Combining Immunotherapy and Targeted Therapies

A study by Armida D’Incecco, MD, of Istituto Toscano Tumori in Livorno, Italy, and colleagues, suggests that combining immunotherapy drugs with other targeted therapies in lung cancer is likely to be beneficial (Abstract 38O).

Dr. D’Incecco’s group studied the expression of PD-L1 and PD-1 in a group of 123 patients with non–small cell lung cancer and also analyzed the patients’ cancers for mutations in two other molecules, EGFR—which is targeted by the existing drugs gefitinib (Iressa) and erlotinib (Tarceva)—and KRAS. The researchers found that tumors that expressed PD-L1 also tended to carry EGFR mutations and that PD-1 expression in the tissue sample was associated with KRAS mutations.

Among patients whose tumors carried EGFR mutations, and who were treated with targeted therapies, those whose tumors were also PD-L1–positive 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.

Dr. Soria commented that if the suggested correlation between PD-L1 expression and EGFR mutation 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.” Trials to explore this relationship are underway, he said.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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