We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Open Drawer MenuClose Drawer Menu
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine
Systematic Review

PD-L1 expression and outcome of advanced melanoma patients treated with anti-PD-1/PD-L1 agents: a meta-analysis

    Omar Abdel-Rahman

    *Author for correspondence:

    E-mail Address: omar.abdelrhman@med.asu.edu.eg

    Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Search for more papers by this author

    Published Online:3 Aug 2016https://doi.org/10.2217/imt-2016-0025

    Abstract

    Aim: This meta-analysis aims at assessing the correlation of PD-L1 levels and response PD-1/PD-L1 inhibitors in advanced malignant melanoma. Methods: Eligible studies included those evaluating PD-1/PD-L1 inhibitors in advanced melanoma and correlating the outcomes to PD-L1 levels. Results: After preclusion of ineligible studies, 11 studies were included. For PD-L1 >1% patients versus PD-L1 <1% patients treated with PD-1/PD-L1 targeted agents, the OR of ORR was 2.81 (95% CI: 1.64–4.82; p = 0.0002); while for PD-L1 >5% patients versus PD-L1 <5% patients, it was 2.22 (95% CI: 1.71–2.87; p < 0.00001). Conclusion: The current analysis indicates the value of PD-L1 positivity in predicting higher response from PD-1/PD-L1 agents. This molecular predictor – together with other predictors – may help further individualize treatment options for metastatic melanoma patients.

    Papers of special note have been highlighted as: • of interest

    References

    • 1 Song X, Zhao Z, Barber B, Farr AM, Ivanov B, Novich M. Overall survival in patients with metastatic melanoma. Curr. Med. Res. Opin. 31(5), 987–991 (2015).
      MedlineGoogle Scholar
    • 2 Bishop KD, Olszewski AJ. Epidemiology and survival outcomes of ocular and mucosal melanomas: a population-based analysis. Int. J. Cancer 134(12), 2961–2971 (2014).
      Medline CASGoogle Scholar
    • 3 Michielin O, Höller C. Gaining momentum: New options and opportunities for the treatment of advanced melanoma. Cancer Treat. Rev. 41(8), 660–670 (2015).
      Medline CASGoogle Scholar
    • 4 Weise AM, Flaherty LE. New options for the adjuvant treatment of cutaneous melanoma? Curr. Oncol. Rep. 16(11), 1–6 (2014).
      CASGoogle Scholar
    • 5 Abdel-Rahman O, Elhalawani H, Ahmed H. Doublet BRAF/MEK inhibition versus single-agent BRAF inhibition in the management of BRAF-mutant advanced melanoma, biological rationale and meta-analysis of published data. Clin. Transl. Oncol. 1–11 (2015) (Epub ahead of print).
      Google Scholar
    • 6 Hodi FS, Lee S, Mcdermott DF et al. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA 312(17), 1744–1753 (2014).
      Medline CASGoogle Scholar
    • 7 Larkin J, Chiarion-Sileni V, Gonzalez R et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373(1), 23–34 (2015).
      Medline CASGoogle Scholar
    • 8 Robert C, Schachter J, Long GV et al. Pembrolizumab versus ipilimumab in advanced melanoma. N. Engl. J. Med. 372(26), 2521–2532 (2015). • For patients receiving nivolumab in this study, the overall response rate (ORR) was 52.7% in PD-L1-positive tumors versus 33.1% in PD-L1-negative tumors.
      Medline CASGoogle Scholar
    • 9 Tumeh PC, Harview CL, Yearley JH et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515(7528), 568–571 (2014).
      Medline CASGoogle Scholar
    • 10 Herbst RS, Soria J-C, Kowanetz M et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515(7528), 563–567 (2014).
      Medline CASGoogle Scholar
    • 11 Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann. Intern. Med. 151(4), 264–269 (2009).
      MedlineGoogle Scholar
    • 12 Postow MA, Chesney J, Pavlick AC et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med. 372(21), 2006–2017 (2015).
      MedlineGoogle Scholar
    • 13 Wolchok JD, Kluger HM, Callahan MK et al. Safety and clinical activity of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in combination with ipilimumab in patients (pts) with advanced melanoma (MEL). J. Clin. Oncol. 31(Suppl.), Abstract 9012 (2013).
      Google Scholar
    • 14 Grosso J, Horak CE, Inzunza D et al. Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients (pts) with advanced solid tumors treated with nivolumab (anti-PD-1; BMS-936558; ONO-4538). J. Clin. Oncol. 31(Suppl.), Abstract 3016 (2013).
      Google Scholar
    • 15 Weber JS, D’angelo SP, Minor D et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, Phase 3 trial. Lancet Oncol. 16(4), 375–384 (2015).
      Medline CASGoogle Scholar
    • 16 Robert C, Long GV, Brady B et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 372(4), 320–330 (2015).
      Medline CASGoogle Scholar
    • 17 Hodi FS, Sznol M, Kluger HM et al. Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a Phase I trial. ASCO Annual Meeting Proceedings 32(Suppl. 5s), Abstract 9002 (2014).
      Google Scholar
    • 18 Weber JS, Kudchadkar RR, Yu B et al. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or-naive melanoma. J. Clin. Oncol. 31(34), 4311–4318 (2013).
      Medline CASGoogle Scholar
    • 19 Ribas A, Puzanov I, Dummer R et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, Phase 2 trial. Lancet Oncol. 16(8), 908–918 (2015).
      Medline CASGoogle Scholar
    • 20 Kefford R, Ribas A, Hamid O et al. Clinical efficacy and correlation with tumor PD-L1 expression in patients (pts) with melanoma (MEL) treated with the anti-PD-1 monoclonal antibody MK-3475. J. Clin. Oncol. 32(Suppl. 5s), Abstract 3005 (2014).
      Google Scholar
    • 21 Hamid O, Sosman JA, Lawrence DP et al. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM). J. Clin. Oncol. 31(Suppl.), Abstract 9010 (2013).
      MedlineGoogle Scholar
    • 22 Larkin J, Lao CD, Urba WJ et al. Efficacy and safety of nivolumab in patients with BRAF V600 mutant and BRAF wild-type advanced melanoma A pooled analysis of 4 clinical trials. JAMA Oncol. 1(4), 433–440 (2015).
      MedlineGoogle Scholar
    • 23 Abdel-Rahman O, Elhalawani H, Fouad M. Risk of cutaneous toxicities in patients with solid tumors treated with immune checkpoint inhibitors: a meta-analysis. Future Oncol. 11(17), 2471–2484 (2015).
      CASGoogle Scholar
    • 24 Abdel-Rahman O. Immune checkpoints aberrations and gastric cancer; assessment of prognostic value and evaluation of therapeutic potentials. Crit. Rev. Oncol. Hematol. 97, 65–71 (2015).
      MedlineGoogle Scholar
    • 25 Borghaei H, Paz-Ares L, Horn L et al. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N. Engl. J. Med. 373(17), 1627–1639 (2015).
      Medline CASGoogle Scholar
    • 26 Brahmer J, Reckamp KL, Baas P et al. Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer. N. Engl. J. Med. 373(2), 123–135 (2015).
      Medline CASGoogle Scholar
    • 27 Massi D, Brusa D, Merelli B et al. PD-L1 marks a subset of melanomas with a shorter overall survival and distinct genetic and morphological characteristics. Ann. Oncol. 25(12), 2433–2442 (2014).
      Medline CASGoogle Scholar
    • 28 Carbognin L, Pilotto S, Milella M et al. Differential activity of nivolumab, pembrolizumab and MPDL3280A according to the tumor expression of programmed death-ligand-1 (PD-L1): sensitivity analysis of trials in melanoma, lung and genitourinary cancers. PLoS ONE 10(6), e0130142 (2015).
      MedlineGoogle Scholar
    • 29 Abdel-Rahman O. Correlation between PD-L1 expression and outcome of NSCLC patients treated with anti-PD-1/PD-L1 agents: a meta-analysis. Crit. Rev. Oncol. Hematol. 101, 75–85 (2016).
      MedlineGoogle Scholar
    • 30 Abdel-Rahman O, Elhalawani H, Fouad M. Risk of elevated transaminases in cancer patients treated with immune checkpoint inhibitors: a meta-analysis. Expert Opin. Drug Saf. 14(10), 1507–1518 (2015).
      Medline CASGoogle Scholar
    • 31 Abdel-Rahman O, ElHalawani H, Fouad M. Risk of endocrine complications in cancer patients treated with immune check point inhibitors; a meta-analysis. Future Oncol. 12(3), 413–425 (2015).
      Google Scholar
    • 32 Abdel-Rahman O, ElHalawani H, Fouad M. Risk of gastrointestinal complications in cancer patients treated with immune checkpoint inhibitors; a meta-analysis. Immunotherapy 7(11), 1213–1227 (2015)
      CASGoogle Scholar
    • 33 Westin JR, Chu F, Zhang M et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, Phase 2 trial. Lancet Oncol. 15(1), 69–77 (2014).
      Medline CASGoogle Scholar