Immune to Cancer: The CRI Blog




Checkpoint Inhibitors Benefit Lung Cancer Patients in Clinical Trials

Illustration of the lungs

On Sunday at the European Society of Medical Oncology (ESMO) 2016 Congress, Merck revealed results of two clinical trials that treated lung cancer patients with immunotherapy and could pave the way for its use as a first-line treatment option. In both trials, patients with metastatic and previously untreated non-small cell lung carcinoma (NSCLC) benefited from treatment with checkpoint blockade using the anti-PD-1 drug pembrolizumab. The results from the trials were published in the New England Journal of Medicine and The Lancet.

In the phase 3 KEYNOTE-024 trial, pembrolizumab treatment alone improved patient outcomes compared to chemotherapy alone. In addition to reducing the risk of death by 40%, pembrolizumab-treated patients were more likely to respond (44.8% compared to 27.8% in the chemotherapy arm) and also went longer without their disease progressing: the median progression-free survival time was 10.3 months in the immunotherapy arm compared to 6.0 months in the chemotherapy arm. These results led the FDA to grant Breakthrough Therapy Designation and Priority Review to this application of pembrolizumab, and set a target action date of December 24, 2016.

One aspect of this trial worth noting is that it only treated patients whose tumors expressed high levels of PD-L1, which activates the same PD-1 pathway that pembrolizumab is designed to block. There’s been a big push in immunotherapy recently to identify and develop biomarkers that can help doctors predict which patients are most likely to benefit from immunotherapy, and trials like this may help determine the best ways to take advantage of these biomarkers.

Merck also announced results from their phase 1/2 KEYNOTE-021 trial testing the combination of pembrolizumab and chemotherapy in patients with metastatic and previously untreated NSCLC. However, in this trial, patients were selected regardless of PD-L1 expression. Even so, combination-treated patients were roughly twice as likely to respond compared to chemotherapy alone (55% response rate compared to 28%). Combining immunotherapy and chemotherapy also reduced the risk of disease progression or death by 47%.

This combination of checkpoint immunotherapy and chemotherapy demonstrates an important concept. It was already known that checkpoint inhibition is more likely to work in patients who have a pre-existing anti-tumor immune response. Building on that, this trial shows that, in patients who might not already have pre-existing immune responses, chemotherapy may improve the effectiveness of checkpoint blockade, perhaps by disrupting the tumor and releasing cellular debris that attracts attention of the immune system. Tuned to the presence of tumor cells, immune cells are better equipped to respond with assistance of checkpoint inhibition.

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