Circulating immune biomarkers as predictors of the response to pembrolizumab and weekly low dose carboplatin and paclitaxel in NSCLC and poor PS: An interim analysis

  • Authors:
    • Marcelo Bonomi
    • Tamjeed Ahmed
    • Safoa Addo
    • Mitra Kooshki
    • Dario Palmieri
    • Beverly J. Levine
    • Jimmy Ruiz
    • Stefan Grant
    • William J. Petty
    • Pierre L. Triozzi
  • View Affiliations

  • Published online on: November 19, 2018     https://doi.org/10.3892/ol.2018.9724
  • Pages: 1349-1356
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Abstract

The combination of standard‑dose chemotherapy and immunotherapy has been shown to be beneficial for patients with non‑small cell lung cancer (NSCLC) with good performance status (PS). However, treatment options for patients with poor PS are limited. In the present study, the feasibility and immunological effects of low‑dose chemotherapy with carboplatin and paclitaxel combined with immunotherapy with pembrolizumab were examined in patients with metastatic NSCLC and a poor PS. Patients with advanced NSCLC and a PS of 2 were randomized to single‑agent pembrolizumab at 200 mg every 3 weeks or pembrolizumab combined with weekly carboplatin area under the curve 1 and paclitaxel 25 mg/m2. Blood for circulating immune cell phenotyping, soluble program death ligand 1 (sPD‑L1) and immune‑modulatory microRNAs (miRNAs) was collected prior to treatment and at weeks 4 and 7. Ten patients were randomized to the combination arm and 10 to the single‑agent arm. Therapy was well tolerated. Four patients discontinued carboplatin due to hypersensitivity reactions but continued pembrolizumab and paclitaxel treatments. Increases in activated CD4+ T cells and in immune‑regulatory miRNA, and decreases in myeloid derived suppressor cells were observed in the blood of patients in the combination arm and not in the single‑agent arm. Changes in circulating regulatory T cells and sPD‑L1 were not observed. Seven patients in the combination arm manifested a partial response compared with only two in the single‑agent arm. Weekly low‑dose chemotherapy carboplatin and paclitaxel was well tolerated and immunologically active when combined with pembrolizumab in patients with advanced NSCLC and a PS of 2. This combination merits further study in this patient population.
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January-2019
Volume 17 Issue 1

Print ISSN: 1792-1074
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Spandidos Publications style
Bonomi M, Ahmed T, Addo S, Kooshki M, Palmieri D, Levine BJ, Ruiz J, Grant S, Petty WJ, Triozzi PL, Triozzi PL, et al: Circulating immune biomarkers as predictors of the response to pembrolizumab and weekly low dose carboplatin and paclitaxel in NSCLC and poor PS: An interim analysis. Oncol Lett 17: 1349-1356, 2019
APA
Bonomi, M., Ahmed, T., Addo, S., Kooshki, M., Palmieri, D., Levine, B.J. ... Triozzi, P.L. (2019). Circulating immune biomarkers as predictors of the response to pembrolizumab and weekly low dose carboplatin and paclitaxel in NSCLC and poor PS: An interim analysis. Oncology Letters, 17, 1349-1356. https://doi.org/10.3892/ol.2018.9724
MLA
Bonomi, M., Ahmed, T., Addo, S., Kooshki, M., Palmieri, D., Levine, B. J., Ruiz, J., Grant, S., Petty, W. J., Triozzi, P. L."Circulating immune biomarkers as predictors of the response to pembrolizumab and weekly low dose carboplatin and paclitaxel in NSCLC and poor PS: An interim analysis". Oncology Letters 17.1 (2019): 1349-1356.
Chicago
Bonomi, M., Ahmed, T., Addo, S., Kooshki, M., Palmieri, D., Levine, B. J., Ruiz, J., Grant, S., Petty, W. J., Triozzi, P. L."Circulating immune biomarkers as predictors of the response to pembrolizumab and weekly low dose carboplatin and paclitaxel in NSCLC and poor PS: An interim analysis". Oncology Letters 17, no. 1 (2019): 1349-1356. https://doi.org/10.3892/ol.2018.9724