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Expert Opinion on Biological Therapy Volume 16, 2016 - Issue 3
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Drug Evaluations

Pembrolizumab for the treatment of non-small cell lung cancer

Sung Hee LimDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
,
Jong-Mu SunDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
,
Se-Hoon LeeDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
,
Jin Seok AhnDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
,
Keunchil ParkDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
&
Myung-Ju AhnDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South KoreaCorrespondence[email protected]
Pages 397-406 | Received 29 Nov 2015, Accepted 20 Jan 2016, Published online: 11 Feb 2016

References

  • Reference annotations
  • • Of interest
  • •• Of considerable interest
  • Topalian SL, Weiner GJ, Pardoll DM. Cancer immunotherapy comes of age. J Clin Oncol. 2011;29:4828–4836. doi:10.1200/JCO.2011.38.0899.
  • Maeurer MJ, Gollin SM, Martin D, et al. Tumor escape from immune recognition: lethal recurrent melanoma in a patient associated with downregulation of the peptide transporter protein TAP-1 and loss of expression of the immunodominant MART-1/Melan-A antigen. J Clin Invest. 1996;98:1633–1641. doi:10.1172/JCI118958.
  • Munn DH, Sharma MD, Lee JR, et al. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science. 2002;297:1867–1870. doi:10.1126/science.1073514.
  • Yokokawa J, Cereda V, Remondo C, et al. Enhanced functionality of CD4+CD25(high)FoxP3+ regulatory T cells in the peripheral blood of patients with prostate cancer. Clin Cancer Res. 2008;14:1032–1040. doi:10.1158/1078-0432.CCR-07-2056.
  • Gasparoto TH, De Souza Malaspina TS, Benevides L, et al. Patients with oral squamous cell carcinoma are characterized by increased frequency of suppressive regulatory T cells in the blood and tumor microenvironment. Cancer Immunol Immunother. 2010;59:819–828. doi:10.1007/s00262-009-0803-7.
  • Jacobs JF, Nierkens S, Figdor CG, et al. Regulatory T cells in melanoma: the final hurdle towards effective immunotherapy? Lancet Oncol. 2012;13:e32–42. doi:10.1016/S1470-2045(11)70155-3.
  • Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372:311–319. doi:10.1056/NEJMoa1411087.
  • Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515:558–562. doi:10.1038/nature13904.
  • Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366:2455–2465. doi:10.1056/NEJMoa1200694.

•• A landmark study of nivolumab as PD-1 antibody demonstrating robust and durable response with prolonged survival in heavily treated malignant melanoma, renal cell carcinoma, and non-small cell lung cancer for the first time.

  • Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–723. doi:10.1056/NEJMoa1003466.

•• A pivotal study of ipilimumab as CTLA-4 antibody showing survival advantage over conventional therapy in malignant melanoma, leading to FDA approval.

  • Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271:1734–1736.
  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–264. doi:10.1038/nrc3239.
  • Lynch TJ, Bondarenko I, Luft A, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012;30:2046–2054. doi:10.1200/JCO.2011.38.4032.
  • Ishida Y, Agata Y, Shibahara K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. Embo J. 1992;11:3887–3895.
  • Dong H, Zhu G, Tamada K, et al. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5:1365–1369. doi:10.1038/70932.
  • Keir ME, Butte MJ, Freeman GJ, et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704. doi:10.1146/annurev.immunol.26.021607.090331.
  • Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8:793–800. doi:10.1038/nm730.
  • Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28:3167–3175. doi:10.1200/JCO.2009.26.7609.
  • Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012;24:207–212. doi:10.1016/j.coi.2011.12.009.
  • Iwai Y, Ishida M, Tanaka Y, et al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA. 2002;99:12293–12297. doi:10.1073/pnas.192461099.
  • Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369:134–144. doi:10.1056/NEJMoa1305133.
  • Velcheti V, Schalper KA, Carvajal DE, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest. 2014;94:107–116. doi:10.1038/labinvest.2013.130.
  • Chen Y-B, Mu C-Y, Huang J-A. Clinical significance of programmed death-1 ligand-1 expression in patients with non-small cell lung cancer: a 5-year-follow-up study. Tumori. 2012;98:751–755. doi:10.1700/1217.13499.
  • Patnaik A, Kang SP, Rasco D, et al. Phase I study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. Clin Cancer Res. 2015;21:4286–4293. doi:10.1158/1078-0432.CCR-14-2607.
  • Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384:1109–1117. doi:10.1016/S0140-6736(14)60958-2.
  • Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018–2028. doi:10.1056/NEJMoa1501824.

• This study demonstrates pembrolizumab showed high response rate and durable response which is correlated with PD-L1 expression in heavily treated non-small cell cancer, resulting in FDA approval.

  • Herbst D-WK RS, Felip E, et al. KEYNOTE-010: Phase 2/3 study of pembrolizumab (MK-3475) vs docetaxel for PD-L1–positive NSCLC after platinum-based therapy. ESMO Asia 2015 Presidential Symposium Abstract LBA3. 2015.
  • Herbst RS, Baas P, Kim D-W, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet.

•• A pivotal phase III trial demonstrating that two different doses of pembrolizumab significantly improved overall survival, progression-free survival, and response rate compared with docetaxel as second-line therapy in PD-L1 expressed non-small cell lung cancer.

  • Tony Mok Y-LW, Patricia A, Watson JZ, et al. Rangwala and Gilberto Lopes. Phase 3 KEYNOTE-042 trial of pembrolizumab (MK-3475) versus platinum doublet chemotherapy in treatment-naive patients (pts) with PD-L1–positive advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2015;33:suppl; abstr TPS8105.
  • Keytruda-Merck.com. [cited 2015 Dec]. Available at https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf; 2015.
  • Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–135. doi:10.1056/NEJMoa1504627.
  • Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–1639. doi:10.1056/NEJMoa1507643.
  • Herbst RS, Soria J-C, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–567. doi:10.1038/nature14011.
  • 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. 2015;10:e0130142. doi:10.1371/journal.pone.0130142.
  • Antoni Ribas CR, Stephen Hodi F, et al. Association of response to programmed death receptor 1 (PD-1) blockade with pembrolizumab (MK-3475) with an interferon-inflammatory immune gene signature. J Clin Oncol. 33, 2015 (suppl; abstr 3001).
  • Veena S, Kei M, Bang Y-J, et al. Correlation of gene expression signatures and clinical outcomes in patients with advanced gastric cancer treated with pembrolizumab (MK-3475). J Clin Oncol. 33, 2015 (suppl; abstr 3026).
  • Lawrence MS, Stojanov P, Polak P, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214–218. doi:10.1038/nature12213.
  • Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–128. doi:10.1126/science.aaa1348.

•• This paper describes the importance of mutation load in tumor associated with favorable clinical outcome in non-small cell lung cancer patients treated with PD-1 antibody, suggesting predictive marker

  • Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–2520. doi:10.1056/NEJMoa1500596.
  • Lin EI, Tseng L-H, Gocke CD, et al. Mutational profiling of colorectal cancers with microsatellite instability. Oncotarget. 2015;6:42334–42344. doi:10.18632/oncotarget.5997.
  • Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371:2189–2199. doi:10.1056/NEJMoa1406498.
  • Okazaki T, Chikuma S, Iwai Y, et al. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol. 2013;14:1212–1218. doi:10.1038/ni.2762.
  • Curran MA, Montalvo W, Yagita H, et al. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci USA. 2010;107:4275–4280. doi:10.1073/pnas.0915174107.

• A pivotal phase III trial demonstrating significant higher response and survival benefit with combination of nivolumab and ipilimumab in malignant melanoma compared with monotherapy.

  • Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372:2006–2017. doi:10.1056/NEJMoa1414428.
  • Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34. doi:10.1056/NEJMoa1504030.
  • Zeng J, See AP, Phallen J, et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys. 2013;86:343–349. doi:10.1016/j.ijrobp.2012.12.025.
  • Dovedi SJ, Adlard AL, Lipowska-Bhalla G, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014;74:5458–5468. doi:10.1158/0008-5472.CAN-14-1258.
  • Doherty MK, Jao K, Shepherd FA, et al. Central nervous system pseudoprogression in a patient treated with PD-1 checkpoint inhibitor. J Thorac Oncol. 2015;10:e100–1. doi:10.1097/JTO.0000000000000587.
  • Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15:7412–7420. doi:10.1158/1078-0432.CCR-09-1624.
  • Hoos A, Wolchok JD, Humphrey RW, et al. CCR 20th anniversary commentary: immune-related response criteria-capturing clinical activity in immuno-oncology. Clin Cancer Res. 2015;21:4989–4991. doi:10.1158/1078-0432.CCR-14-3128.

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