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Lung Cancer Patients Live Longer with Drug Targeting T cells

Feb 24, 2016 1:00:46 PM / by Daisy Goodrich

 The majority of lung cancers are of the non-small-cell subtype. Of these, about two-thirds are positive for PD-L1 proteins, which modulate T cells. Newer cancer therapeutics target the PD-1 pathway and have better outcome in comparison to chemotherapy. Image credits: https://en.wikipedia.org/wiki/File:Pie_chart_of_lung_cancers.svgPembrolizumab, a newer drug, harnesses T cells to tackle cancer. For certain lung cancer patients, this means having twice the lifespan than that accorded by chemotherapy! 

For patients battling lung cancer, the majority are of the non-small-cell lung carcinoma (NSCLC) subtype. Among these, a subgroup of tumors produce a protein, PD-L1, which enables escape from attack by the patient’s immune system (see here). Specifically, PD-L1 binds to PD-1 receptors on T cells, thereby preventing T cells from activating, proliferating, and/or producing cytokines, so that T cells do not mount an attack towards the PD-L1-positive tumor cells.

Pembrolizumab is a newer cancer immunotherapy approved for PD-L1-positive lung cancer patients with metastatic NSCLC and for whom chemotherapy treatment was unsuccessful. To explore further therapeutic benefits of this antibody drug, a clinical trial (KEYNOTE-10 study) was undertaken to investigate a higher drug dose in comparison to the current 2 mg/kg.[1] We have previously noted the importance of dose levels for clinical outcome (see here).

 Patients were randomized into 10 mg/kg and 2 mg/kg pembrolizumab arms, and into a chemotherapy arm (75 mg/m2 docetaxel). One goal of this study was to determine the median overall survival (time from randomization to death due to any cause) for each treatment regimen.

Results showed the overall survival to be 12.7 and 10.4 months for the 10 mg/kg and 2 mg/kg pembrolizumab arms, respectively. These were statistically different from the overall survival for the chemotherapy arm, at 8.5 months.

When patients in this study were categorized by PD-L1 levels in their biopsies, those with >50% of PD-L1-expressing cells in their tumors had better overall survival than the entire PD-L1-positive group. For the PD-L1-high group, overall survival was 17.3 and 14.9 months in the 10 mg/kg and 2 mg/kg pembrolizumab arms, and 8.2 months in the chemotherapy arm. Hence, pembrolizumab at 10 mg/kg accorded the PD-L1-high lung cancer patients over twice the life-span in comparison to chemotherapy!

The results of this study contribute to the growing body of evidence that supports the manipulation of T cells as an impactful cancer therapeutic (see here). If patients can be stratified for the level of PD-L1 in their tumors, pembrolizumab is even more beneficial for patients with higher PD-L1 levels. While the current study explored an anti-receptor antibody for T cells, we have also discussed an anti-ligand antibody therapeutic (see here).

HemaCare fuels scientific discoveries through providing several types of T cells for research purposes. We salute all researchers who have contributed to the knowledge base on T cells that have led to advancements for help for lung cancer patients. For more information on the types of human blood cells that we offer, call today at (877) 397-3087.

Reference

  1. Herbst RS, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2015 Dec 18. pii: S0140-6736(15)01281-7.

Topics: clinical trial, PD-1, PD-L1, pembrolizumab, Immunotherapy (Immunology)

Daisy Goodrich

Written by Daisy Goodrich

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