Top

BMC Cancer

Published in:

Open Access 01-12-2023 | NSCLC | Research

Clinical benefit of pembrolizumab in treatment of first line non-small cell lung cancer: a systematic review and meta-analysis of clinical characteristics

Authors: Wenjie Liu, Gengwei Huo, Peng Chen

Published in: BMC Cancer | Issue 1/2023

Abstract

Objective

Pembrolizumab has become an integral first line therapeutic agent for non-small cell lung cancer (NSCLC), but its potential predictive role in clinical and molecular characteristics remains to be clarified. Accordingly, we performed a systematic review and meta-analysis to evaluate the clinical benefit of pembrolizumab in treatment of first line NSCLC and to select individuals with the greatest potential benefit from pembrolizumab therapy, in order to obtain a more accurate treatment of NSCLC in immunotherapy.

Methods

Mainstream oncology datasets and conferences were searched for randomized clinical trials (RCTs) published before August 2022. RCTs involved individuals with first line NSCLC treated with pembrolizumab monotherapy or in combination with chemotherapy. Two authors independently selected the studies, extracted data, and assessed the risk of bias. The basic characteristics of the included studies were recorded, along with 95 percent confidence intervals (CI) and hazard ratios (HR) for all patients and subgroups. The primary endpoint was overall survival (OS), and secondary endpoints was progression-free survival (PFS). Pooled treatment data were estimated using the inverse variance-weighted method.

Results

Five RCTs involving 2,877 individuals were included in the study. Pembrolizumab-based therapy significantly improved OS (HR 0.66; CI 95%, 0.55–0.79; p < 0.00001) and PFS (HR 0.60; CI 95%, 0.40–0.91; p = 0.02) compared with chemotherapy. OS was substantially enhanced in individuals aged < 65 years (HR 0.59; CI 95%, 0.42–0.82; p = 0.002), males (HR 0.74; CI 95%, 0.65–0.83; p < 0.00001), with a smoking history (HR 0.65; CI 95%, 0.52–0.82; p = 0.0003), with PD-L1 tumor proportion score (TPS) < 1% (HR 0.55; CI 95%, 0.41–0.73; p < 0.0001) and TPS ≥ 50% (HR 0.66; CI 95%, 0.56–0.76; p < 0.00001), but not in individuals aged ≥ 75 years (HR 0.82; CI 95%, 0.56–1.21; p = 0.32), females (HR 0.57; CI 95%, 0.31–1.06; p = 0.08), never smokers (HR 0.57; CI 95%, 0.18–1.80; p = 0.34), or with TPS 1–49% (HR 0.72; CI 95%, 0.52–1.01; p = 0.06). Pembrolizumab significantly prolonged OS in NSCLC patients, regardless of histology type (squamous or non-squamous NSCLC), performance status (PS) (0 or 1), and brain metastatic status (all p < 0.05). Subgroup analysis revealed that pembrolizumab combined with chemotherapy had more favorable HR values than pembrolizumab monotherapy in improving the OS of individuals with different clinical and molecular features.

Conclusion

Pembrolizumab-based therapy is a valuable option for first line treating advanced or metastatic NSCLC. Age, sex, smoking history and PD-L1 expression status can be used to predict the clinical benefit of pembrolizumab. Cautiousness was needed when using pembrolizumab in NSCLC patients aged ≥ 75 years, females, never smokers, or in patients with TPS 1–49%. Furthermore, pembrolizumab in combination with chemotherapy may be a more effective treatment regimen.

Available only for authorised users

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. https://doi.org/10.3322/caac.21551.CrossRefPubMed

Li Z, Huang J, Shen S, Ding Z, Luo Q, Chen Z, et al. SIRT6 drives epithelial-to-mesenchymal transition and metastasis in non-small cell lung cancer via snail-dependent transrepression of KLF4. J Exp Clin Cancer Res. 2018;37(1):323. https://doi.org/10.1186/s13046-018-0984-z.CrossRefPubMedPubMedCentral

Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11(11):3887–95. https://doi.org/10.1002/j.1460-2075.1992.tb05481.x.CrossRefPubMedPubMedCentral

Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10. https://doi.org/10.1016/j.immuni.2013.07.012.CrossRefPubMed

Giroux Leprieur E, Dumenil C, Julie C, Giraud V, Dumoulin J, Labrune S, et al. Immunotherapy revolutionises non-small-cell lung cancer therapy: Results, perspectives and new challenges. Eur J Cancer. 2017;78:16–23. https://doi.org/10.1016/j.ejca.2016.12.041.CrossRefPubMed

Pai-Scherf L, Blumenthal GM, Li H, Subramaniam S, Mishra-Kalyani PS, He K, et al. FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Oncologist. 2017;22(11):1392–9. https://doi.org/10.1634/theoncologist.2017-0078.CrossRefPubMedPubMedCentral

Havel JJ, Chowell D, Chan TA. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer. 2019;19(3):133–50. https://doi.org/10.1038/s41568-019-0116-x.CrossRefPubMedPubMedCentral

Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer. 2016;16(5):275–87. https://doi.org/10.1038/nrc.2016.36.CrossRefPubMedPubMedCentral

Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity. 1999;11(2):141–51. https://doi.org/10.1016/s1074-7613(00)80089-8.CrossRefPubMed

10.

McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med. 2013;2(5):662–73. https://doi.org/10.1002/cam4.106.CrossRefPubMedPubMedCentral

11.

Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34. https://doi.org/10.1084/jem.192.7.1027.CrossRefPubMedPubMedCentral

12.

Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2(3):261–8. https://doi.org/10.1038/85330.CrossRefPubMed

13.

Carter L, Fouser LA, Jussif J, Fitz L, Deng B, Wood CR, et al. PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur J Immunol. 2002;32(3):634–43. https://doi.org/10.1002/1521-4141(200203)32:3%3c634::AID-IMMU634%3e3.0.CO;2-9.CrossRefPubMed

14.

Chow L, Haddad R, Gupta S, Mahipal A, Mehra R, Tahara M, et al. Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort. J Clin Oncol. 2016;34(32):3838–45. https://doi.org/10.1200/JCO.2016.68.1478.CrossRefPubMedPubMedCentral

15.

Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016;375(19):1823–33. https://doi.org/10.1056/NEJMoa1606774.CrossRefPubMed

16.

Homšek A, Radosavljević D, Miletić N, Spasić J, Jovanović M, Miljković B, et al. Review of the Clinical Pharmacokinetics, Efficacy and Safety of Pembrolizumab. Curr Drug Metab. 2022;23(6):460–72. https://doi.org/10.2174/1389200223666220609125013.CrossRefPubMed

17.

Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, 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(19):4286–93. https://doi.org/10.1158/1078-0432.CCR-14-2607.CrossRefPubMed

18.

Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50. https://doi.org/10.1016/S0140-6736(15)01281-7.CrossRefPubMed

19.

Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(22):2078–92. https://doi.org/10.1056/NEJMoa1801005.CrossRefPubMed

20.

Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018;379(21):2040–51. https://doi.org/10.1056/NEJMoa1810865.CrossRefPubMed

21.

Mok T, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393(10183):1819–30. https://doi.org/10.1016/S0140-6736(18)32409-7.CrossRefPubMed

22.

Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. J Clin Oncol. 2019;37(7):537–46. https://doi.org/10.1200/JCO.18.00149.CrossRefPubMed

23.

Gadgeel S, Rodríguez-Abreu D, Speranza G, Esteban E, Felip E, Dómine M, et al. Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020;38(14):1505–17. https://doi.org/10.1200/JCO.19.03136.CrossRefPubMed

24.

Herbst RS, Garon EB, Kim DW, Cho BC, Perez-Gracia JL, Han JY, et al. Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1-Positive, Advanced Non-Small-Cell Lung Cancer in the KEYNOTE-010 Study. J Clin Oncol. 2020;38(14):1580–90. https://doi.org/10.1200/JCO.19.02446.CrossRefPubMed

25.

Awad MM, Gadgeel SM, Borghaei H, Patnaik A, Yang JC, Powell SF, et al. Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. J Thorac Oncol. 2021;16(1):162–8. https://doi.org/10.1016/j.jtho.2020.09.015.CrossRefPubMed

26.

Hegde PS, Chen DS. Top 10 Challenges in Cancer Immunotherapy. Immunity. 2020;52(1):17–35. https://doi.org/10.1016/j.immuni.2019.12.011.CrossRefPubMed

27.

Munari E, Mariotti FR, Quatrini L, Bertoglio P, Tumino N, Vacca P, et al. PD-1/PD-L1 in Cancer: Pathophysiological, Diagnostic and Therapeutic Aspects. Int J Mol Sci. 2021;22(10). https://doi.org/10.3390/ijms22105123.

28.

Rittmeyer A, Barlesi F, Waterkamp D, Park K, Gandara DDR. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255–65. https://doi.org/10.1016/S0140-6736(16)32517-X.CrossRefPubMed

29.

Borghaei H, Gettinger S, Vokes EE, Chow L, Burgio MA, de Castro CJ, et al. Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non-Small-Cell Lung Cancer. J Clin Oncol. 2021;39(7):723–33. https://doi.org/10.1200/JCO.20.01605.CrossRefPubMedPubMedCentral

30.

Addeo A, Friedlaender A, Banna GL, Weiss GJ. TMB or not TMB as a biomarker: That is the question. Crit Rev Oncol Hematol. 2021;163:103374. https://doi.org/10.1016/j.critrevonc.2021.103374.

31.

Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018;553(7689):446–54. https://doi.org/10.1038/nature25183.CrossRefPubMed

32.

Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693–703. https://doi.org/10.1056/NEJMoa1006448.CrossRefPubMedPubMedCentral

33.

Kim ES, Herbst RS, Wistuba II, Lee JJ, Blumenschein GR Jr, Tsao A, et al. The BATTLE trial: personalizing therapy for lung cancer. Cancer Discov. 2011;1(1):44–53. https://doi.org/10.1158/2159-8274.CD-10-0010.CrossRefPubMedPubMedCentral

34.

Okazaki T, Chikuma S, Iwai Y, Fagarasan S, Honjo T. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol. 2013;14(12):1212–8. https://doi.org/10.1038/ni.2762.CrossRefPubMed

35.

Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350–5. https://doi.org/10.1126/science.aar4060.CrossRefPubMedPubMedCentral

36.

Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28. https://doi.org/10.1056/NEJMoa1501824.CrossRefPubMed

37.

Sul J, Blumenthal GM, Jiang X, He K, Keegan P, Pazdur R. FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1. Oncologist. 2016;21(5):643–50. https://doi.org/10.1634/theoncologist.2015-0498.CrossRefPubMedPubMedCentral

38.

Gadgeel SM, Stevenson JP, Langer CJ, Gandhi L, Borghaei H, Patnaik A, et al. Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study. Lung Cancer. 2018;125:273–81. https://doi.org/10.1016/j.lungcan.2018.08.019.CrossRefPubMed

39.

van Vugt M, Stone JA, De Greef R, Snyder ES, Lipka L, Turner DC, et al. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019;7(1):212. https://doi.org/10.1186/s40425-019-0663-4.CrossRefPubMedPubMedCentral

40.

He BX, Zhong YF, Zhu YB, Deng JJ, Fang MJ, She YL, et al. Deep learning for predicting immunotherapeutic efficacy in advanced non-small cell lung cancer patients: a retrospective study combining progression-free survival risk and overall survival risk. Transl Lung Cancer Res. 2022;11(4):670–85. https://doi.org/10.21037/tlcr-22-244.

41.

Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8. https://doi.org/10.1126/science.aaa1348.

42.

Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P, Halpenny D, et al. Molecular Determinants of Response to Anti-Programmed Cell Death (PD)-1 and Anti-Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non-Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing. J Clin Oncol. 2018;36(7):633–41. https://doi.org/10.1200/JCO.2017.75.3384.CrossRefPubMedPubMedCentral

43.

Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, et al. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017;376(25):2415–26. https://doi.org/10.1056/NEJMoa1613493.CrossRefPubMedPubMedCentral

44.

Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med. 2018;378(22):2093–104. https://doi.org/10.1056/NEJMoa1801946.CrossRefPubMedPubMedCentral

45.

Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71. https://doi.org/10.1038/nature13954.CrossRefPubMedPubMedCentral

46.

Ahamadi M, Freshwater T, Prohn M, Li CH, de Alwis DP, de Greef R, et al. Model-Based Characterization of the Pharmacokinetics of Pembrolizumab: A Humanized Anti-PD-1 Monoclonal Antibody in Advanced Solid Tumors. CPT Pharmacometrics Syst Pharmacol. 2017;6(1):49–57. https://doi.org/10.1002/psp4.12139.CrossRefPubMed

47.

Chatterjee MS, Elassaiss-Schaap J, Lindauer A, Turner DC, Sostelly A, Freshwater T, et al. Population Pharmacokinetic/Pharmacodynamic Modeling of Tumor Size Dynamics in Pembrolizumab-Treated Advanced Melanoma. CPT Pharmacometrics Syst Pharmacol. 2017;6(1):29–39. https://doi.org/10.1002/psp4.12140.CrossRefPubMed

48.

Li H, Yu J, Liu C, Liu J, Subramaniam S, Zhao H, et al. Time dependent pharmacokinetics of pembrolizumab in patients with solid tumor and its correlation with best overall response. J Pharmacokinet Pharmacodyn. 2017;44(5):403–14. https://doi.org/10.1007/s10928-017-9528-y.CrossRefPubMed

49.

Li H, Sun Y, Yu J, Liu C, Liu J, Wang Y. Semimechanistically Based Modeling of Pembrolizumab Time-Varying Clearance Using 4 Longitudinal Covariates in Patients With Non-Small Cell Lung Cancer. J Pharm Sci. 2019;108(1):692–700. https://doi.org/10.1016/j.xphs.2018.10.064.CrossRefPubMed

50.

Salminen A, Kaarniranta K, Kauppinen A. Phytochemicals inhibit the immunosuppressive functions of myeloid-derived suppressor cells (MDSC): Impact on cancer and age-related chronic inflammatory disorders. Int Immunopharmacol. 2018;61:231–40. https://doi.org/10.1016/j.intimp.2018.06.005.CrossRefPubMed

51.

Yusup A, Wang HJ, Rahmutula A, Sayim P, Zhao ZL, Zhang GQ. Clinical features and prognosis in colorectal cancer patients with different ethnicities in Northwest China. World J Gastroenterol. 2013;19(41):7183–8. https://doi.org/10.3748/wjg.v19.i41.7183.CrossRefPubMedPubMedCentral

52.

Quinn BA, Deng X, Colton A, Bandyopadhyay D, Carter JS, Fields EC. Increasing age predicts poor cervical cancer prognosis with subsequent effect on treatment and overall survival. Brachytherapy. 2019;18(1):29–37. https://doi.org/10.1016/j.brachy.2018.08.016.CrossRefPubMed

53.

Elias R, Karantanos T, Sira E, Hartshorn KL. Immunotherapy comes of age: Immune aging & checkpoint inhibitors. J Geriatr Oncol. 2017;8(3):229–35. https://doi.org/10.1016/j.jgo.2017.02.001.CrossRefPubMed

54.

Ferrara R, Mezquita L, Auclin E, Chaput N, Besse B. Immunosenescence and immunecheckpoint inhibitors in non-small cell lung cancer patients: Does age really matter. Cancer Treat Rev. 2017;60:60–8. https://doi.org/10.1016/j.ctrv.2017.08.003.CrossRefPubMed

55.

Van Beek AA, Hoogerland JA, Belzer C, De Vos P, De Vos WM, Savelkoul HF, et al. Interaction of mouse splenocytes and macrophages with bacterial strains in vitro: the effect of age in the immune response. Benef Microbes. 2016;7(2):275–87. https://doi.org/10.3920/BM2015.0094.CrossRefPubMed

56.

Yi X, Yuan Y, Li N, Yi L, Wang C, Qi Y, et al. A mouse model with age-dependent immune response and immune-tolerance for HBV infection. Vaccine. 2018;36(6):794–801. https://doi.org/10.1016/j.vaccine.2017.12.071.CrossRefPubMed

57.

Eichinger KM, Resetar E, Orend J, Anderson K, Empey KM. Age predicts cytokine kinetics and innate immune cell activation following intranasal delivery of IFNγ and GM-CSF in a mouse model of RSV infection. Cytokine. 2017;97:25–37. https://doi.org/10.1016/j.cyto.2017.05.019.CrossRefPubMedPubMedCentral

58.

Quinn KM, Fox A, Harland KL, Russ BE, Li J, Nguyen T, et al. Age-Related Decline in Primary CD8+ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+ T Cells. Cell Rep. 2018;23(12):3512–24. https://doi.org/10.1016/j.celrep.2018.05.057.CrossRefPubMed

59.

Liu R, Zhang S, Ma W, Lu H, Gao J, Gan X, et al. Age-dependent loss of induced regulatory T cell function exacerbates liver ischemia-reperfusion injury. Mol Immunol. 2018;103:251–6. https://doi.org/10.1016/j.molimm.2018.10.004.CrossRefPubMed

60.

Dawany N, Parzych EM, Showe LC, Ertl HC. Age-related changes in the gene expression profile of antigen-specific mouse CD8+ T cells can be partially reversed by blockade of the BTLA/CD160 pathways during vaccination. Aging (Albany NY). 2016;8(12):3272–97. https://doi.org/10.18632/aging.101105.

61.

Xie J, Zhang J, Wu H, Tang X, Liu J, Cheng G, et al. The influences of age on T lymphocyte subsets in C57BL/6 mice. Saudi J Biol Sci. 2017;24(1):108–13. https://doi.org/10.1016/j.sjbs.2016.09.002.CrossRefPubMed

62.

Bandaranayake T, Shaw AC. Host Resistance and Immune Aging. Clin Geriatr Med. 2016;32(3):415–32. https://doi.org/10.1016/j.cger.2016.02.007.CrossRefPubMedPubMedCentral

63.

Elias R, Morales J, Rehman Y, Khurshid H. Immune Checkpoint Inhibitors in Older Adults. Curr Oncol Rep. 2016;18(8):47. https://doi.org/10.1007/s11912-016-0534-9.CrossRefPubMed

64.

Yang Z, Chen Y, Wang Y, Hu M, Qian F, Zhang Y, et al. Pembrolizumab Plus Chemotherapy Versus Chemotherapy Monotherapy as a First-Line Treatment in Elderly Patients (≥75 Years Old) With Non-Small-Cell Lung Cancer. Front Immunol. 2022;13:807575. https://doi.org/10.3389/fimmu.2022.807575.

65.

Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073–81. https://doi.org/10.1093/carcin/bgp127.CrossRefPubMed

66.

Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, et al. Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1. Clin Cancer Res. 2017;23(8):1920–8. https://doi.org/10.1158/1078-0432.CCR-16-1741.CrossRefPubMed

67.

Champiat S, Ferrara R, Massard C, Besse B, Marabelle A, Soria JC, et al. Hyperprogressive disease: recognizing a novel pattern to improve patient management. Nat Rev Clin Oncol. 2018;15(12):748–62. https://doi.org/10.1038/s41571-018-0111-2.CrossRefPubMed

68.

Cook MB, Dawsey SM, Freedman ND, Inskip PD, Wichner SM, Quraishi SM, et al. Sex disparities in cancer incidence by period and age. Cancer Epidemiol Biomarkers Prev. 2009;18(4):1174–82. https://doi.org/10.1158/1055-9965.EPI-08-1118.CrossRefPubMedPubMedCentral

69.

Cook MB, McGlynn KA, Devesa SS, Freedman ND, Anderson WF. Sex disparities in cancer mortality and survival. Cancer Epidemiol Biomarkers Prev. 2011;20(8):1629–37. https://doi.org/10.1158/1055-9965.EPI-11-0246.CrossRefPubMedPubMedCentral

70.

Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331(6024):1565–70. https://doi.org/10.1126/science.1203486.CrossRefPubMed

71.

Conforti F, Pala L, Bagnardi V, De Pas T, Martinetti M, Viale G, et al. Cancer immunotherapy efficacy and patients’ sex: a systematic review and meta-analysis. Lancet Oncol. 2018;19(6):737–46. https://doi.org/10.1016/S1470-2045(18)30261-4.CrossRefPubMed

72.

Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2015;350(6257):207–11. https://doi.org/10.1126/science.aad0095.CrossRefPubMedPubMedCentral

73.

Gupta S, Artomov M, Goggins W, Daly M, Tsao H. Gender Disparity and Mutation Burden in Metastatic Melanoma. J Natl Cancer Inst. 2015;107(11). https://doi.org/10.1093/jnci/djv221.

74.

Xiao D, Pan H, Li F, Wu K, Zhang X, He J. Analysis of ultra-deep targeted sequencing reveals mutation burden is associated with gender and clinical outcome in lung adenocarcinoma. Oncotarget. 2016;7(16):22857–64. https://doi.org/10.18632/oncotarget.8213.

75.

Salem ME, Xiu J, Lenz HJ, Atkins MB, Marshall J. Characterization of tumor mutation load (TML) in solid tumors. J Clin Oncol. 2017;35(15_suppl):11517–11517.

76.

Libert C, Dejager L, Pinheiro I. The X chromosome in immune functions: when a chromosome makes the difference. Nat Rev Immunol. 2010;10(8):594–604. https://doi.org/10.1038/nri2815.CrossRefPubMed

77.

Markle JG, Frank DN, Mortin-Toth S, Robertson CE, Feazel LM, Rolle-Kampczyk U, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013;339(6123):1084–8. https://doi.org/10.1126/science.1233521.CrossRefPubMed

78.

Markle JG, Fish EN. SeXX matters in immunity. Trends Immunol. 2014;35(3):97–104. https://doi.org/10.1016/j.it.2013.10.006.CrossRefPubMed

79.

Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626–38. https://doi.org/10.1038/nri.2016.90.CrossRefPubMed

80.

Org E, Mehrabian M, Parks BW, Shipkova P, Liu X, Drake TA, et al. Sex differences and hormonal effects on gut microbiota composition in mice. Gut Microbes. 2016;7(4):313–22. https://doi.org/10.1080/19490976.2016.1203502.CrossRefPubMedPubMedCentral

81.

Lee CK, Man J, Lord S, Links M, Gebski V, Mok T, et al. Checkpoint Inhibitors in Metastatic EGFR-Mutated Non-Small Cell Lung Cancer-A Meta-Analysis. J Thorac Oncol. 2017;12(2):403–7. https://doi.org/10.1016/j.jtho.2016.10.007.CrossRefPubMed

82.

Youlden DR, Cramb SM, Baade PD. The International Epidemiology of Lung Cancer: geographical distribution and secular trends. J Thorac Oncol. 2008;3(8):819–31. https://doi.org/10.1097/JTO.0b013e31818020eb.CrossRefPubMed

83.

Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin J, Beasley MB, et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 2015;10(9):1243–60. https://doi.org/10.1097/JTO.0000000000000630.CrossRefPubMed

84.

Subramanian J, Morgensztern D, Goodgame B, Baggstrom MQ, Gao F, Piccirillo J, et al. Distinctive characteristics of non-small cell lung cancer (NSCLC) in the young: a surveillance, epidemiology, and end results (SEER) analysis. J Thorac Oncol. 2010;5(1):23–8. https://doi.org/10.1097/JTO.0b013e3181c41e8d.CrossRefPubMed

85.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29. https://doi.org/10.3322/caac.21254.CrossRefPubMed

86.

Janssen-Heijnen ML, Schipper RM, Razenberg PP, Crommelin MA, Coebergh JW. Prevalence of co-morbidity in lung cancer patients and its relationship with treatment: a population-based study. Lung Cancer. 1998;21(2):105–13. https://doi.org/10.1016/s0169-5002(98)00039-7.CrossRefPubMed

87.

Papi A, Casoni G, Caramori G, Guzzinati I, Boschetto P, Ravenna F, et al. COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma. Thorax. 2004;59(8):679–81. https://doi.org/10.1136/thx.2003.018291.CrossRefPubMedPubMedCentral

88.

Rosado-de-Christenson ML, Templeton PA, Moran CA. Bronchogenic carcinoma: radiologic-pathologic correlation. Radiographics. 1994;14(2):429–46. quiz 447–8. https://doi.org/10.1148/radiographics.14.2.8190965.

89.

Hirsch FR, Spreafico A, Novello S, Wood MD, Simms L, Papotti M. The prognostic and predictive role of histology in advanced non-small cell lung cancer: a literature review. J Thorac Oncol. 2008;3(12):1468–81. https://doi.org/10.1097/JTO.0b013e318189f551.CrossRefPubMed

90.

Nichols L, Saunders R, Knollmann FD. Causes of death of patients with lung cancer. Arch Pathol Lab Med. 2012;136(12):1552–7. https://doi.org/10.5858/arpa.2011-0521-OA.CrossRefPubMed

91.

Miyamae Y, Shimizu K, Hirato J, Araki T, Tanaka K, Ogawa H, et al. Significance of epidermal growth factor receptor gene mutations in squamous cell lung carcinoma. Oncol Rep. 2011;25(4):921–8. https://doi.org/10.3892/or.2011.1182.CrossRefPubMed

92.

Caliò A, Nottegar A, Gilioli E, Bria E, Pilotto S, Peretti U, et al. ALK/EML4 fusion gene may be found in pure squamous carcinoma of the lung. J Thorac Oncol. 2014;9(5):729–32. https://doi.org/10.1097/JTO.0000000000000109.CrossRefPubMed

93.

Pan Y, Wang R, Ye T, Li C, Hu H, Yu Y, et al. Comprehensive analysis of oncogenic mutations in lung squamous cell carcinoma with minor glandular component. Chest. 2014;145(3):473–9. https://doi.org/10.1378/chest.12-2679.CrossRefPubMed

94.

König K, Peifer M, Fassunke J, Ihle MA, Künstlinger H, Heydt C, et al. Implementation of Amplicon Parallel Sequencing Leads to Improvement of Diagnosis and Therapy of Lung Cancer Patients. J Thorac Oncol. 2015;10(7):1049–57. https://doi.org/10.1097/JTO.0000000000000570.CrossRefPubMed

95.

Zhao W, Choi YL, Song JY, Zhu Y, Xu Q, Zhang F, et al. ALK, ROS1 and RET rearrangements in lung squamous cell carcinoma are very rare. Lung Cancer. 2016;94:22–7. https://doi.org/10.1016/j.lungcan.2016.01.011.CrossRefPubMed

96.

Masters GA, Temin S, Azzoli CG, Giaccone G, Baker S Jr, Brahmer JR, et al. Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015;33(30):3488–515. https://doi.org/10.1200/JCO.2015.62.1342.CrossRefPubMedPubMedCentral

97.

Novello S, Barlesi F, Califano R, Cufer T, Ekman S, Levra MG, et al. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v1–1v27. https://doi.org/10.1093/annonc/mdw326.

98.

Socinski MA, Obasaju C, Gandara D, Hirsch FR, Bonomi P, Bunn P, et al. Clinicopathologic Features of Advanced Squamous NSCLC. J Thorac Oncol. 2016;11(9):1411–22. https://doi.org/10.1016/j.jtho.2016.05.024.CrossRefPubMed

99.

Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26(21):3543–51. https://doi.org/10.1200/JCO.2007.15.0375.CrossRefPubMed

100.

Tan EH, Rolski J, Grodzki T, Schneider CP, Gatzemeier U, Zatloukal P, et al. Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and i.v. vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer. Ann Oncol. 2009;20(7):1249–56. https://doi.org/10.1093/annonc/mdn774.

101.

Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012;30(17):2055–62. https://doi.org/10.1200/JCO.2011.39.5848.CrossRefPubMed

102.

Hoang T, Dahlberg SE, Schiller JH, Johnson DH. Does histology predict survival of advanced non-small cell lung cancer patients treated with platin-based chemotherapy? An analysis of the Eastern Cooperative Oncology Group Study E1594. Lung Cancer. 2013;81(1):47–52. https://doi.org/10.1016/j.lungcan.2013.03.018.CrossRefPubMed

103.

Kelly K, Chansky K, Mack PC, Lara PN Jr, Hirsch FR, Franklin WA, et al. Chemotherapy outcomes by histologic subtypes of non-small-cell lung cancer: analysis of the southwest oncology group database for antimicrotubule-platinum therapy. Clin Lung Cancer. 2013;14(6):627–35. https://doi.org/10.1016/j.cllc.2013.06.010.CrossRefPubMedPubMedCentral

104.

Ritzwoller DP, Carroll NM, Delate T, Hornbrook MC, Kushi L, Aiello Bowles EJ, et al. Patterns and predictors of first-line chemotherapy use among adults with advanced non-small cell lung cancer in the cancer research network. Lung Cancer. 2012;78(3):245–52. https://doi.org/10.1016/j.lungcan.2012.09.008.CrossRefPubMed

105.

Søgaard M, Thomsen RW, Bossen KS, Sørensen HT, Nørgaard M. The impact of comorbidity on cancer survival: a review. Clin Epidemiol. 2013;5(Suppl 1):3–29. https://doi.org/10.2147/CLEP.S47150.CrossRefPubMedPubMedCentral

106.

Tabchi S, Kassouf E, Florescu M, Tehfe M, Blais N. Factors influencing treatment selection and survival in advanced lung cancer. Curr Oncol. 2017;24(2):e115–115e122. https://doi.org/10.3747/co.24.3355.

107.

Morabito A, Gebbia V, Di Maio M, Cinieri S, Viganò MG, Bianco R, et al. Randomized phase III trial of gemcitabine and cisplatin vs. gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status of 2: the CAPPA-2 study. Lung Cancer. 2013;81(1):77–83. https://doi.org/10.1016/j.lungcan.2013.04.008.

108.

Mörth C, Valachis A. Single-agent versus combination chemotherapy as first-line treatment for patients with advanced non-small cell lung cancer and performance status 2: a literature-based meta-analysis of randomized studies. Lung Cancer. 2014;84(3):209–14. https://doi.org/10.1016/j.lungcan.2014.03.015.CrossRefPubMed

109.

Strøm HH, Bremnes RM, Sundstrøm SH, Helbekkmo N, Aasebø U. Poor prognosis patients with inoperable locally advanced NSCLC and large tumors benefit from palliative chemoradiotherapy: a subset analysis from a randomized clinical phase III trial. J Thorac Oncol. 2014;9(6):825–33. https://doi.org/10.1097/JTO.0000000000000184.CrossRefPubMedPubMedCentral

110.

Caires-Lima R, Cayres K, Protásio B, Caires I, Andrade J, Rocha L, et al. Palliative chemotherapy outcomes in patients with ECOG-PS higher than 1. Ecancermedicalscience. 2018;12:831. https://doi.org/10.3332/ecancer.2018.831.CrossRefPubMedPubMedCentral

111.

Tan PS, Lopes G, Acharyya S, Bilger M, Haaland B. Bayesian network meta-comparison of maintenance treatments for stage IIIb/IV non-small-cell lung cancer (NSCLC) patients with good performance status not progressing after first-line induction chemotherapy: results by performance status, EGFR mutation, histology and response to previous induction. Eur J Cancer. 2015;51(16):2330–44. https://doi.org/10.1016/j.ejca.2015.07.007.CrossRefPubMed

112.

Socinski MA, Obasaju C, Gandara D, Hirsch FR, Bonomi P, Bunn PA Jr, et al. Current and Emergent Therapy Options for Advanced Squamous Cell Lung Cancer. J Thorac Oncol. 2018;13(2):165–83. https://doi.org/10.1016/j.jtho.2017.11.111.CrossRefPubMed

113.

Rizvi NA, Hellmann MD, Brahmer JR, Juergens RA, Borghaei H, Gettinger S, et al. Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2016;34(25):2969–79. https://doi.org/10.1200/JCO.2016.66.9861.CrossRefPubMedPubMedCentral

114.

Peters S, Gettinger S, Johnson ML, Jänne PA, Garassino MC, Christoph D, et al. Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH). J Clin Oncol. 2017;35(24):2781–9. https://doi.org/10.1200/JCO.2016.71.9476.CrossRefPubMedPubMedCentral

115.

Ksienski D, Wai ES, Croteau N, Freeman AT, Chan A, Fiorino L, et al. Pembrolizumab for advanced nonsmall cell lung cancer: Efficacy and safety in everyday clinical practice. Lung Cancer. 2019;133:110–6. https://doi.org/10.1016/j.lungcan.2019.05.005.CrossRefPubMed

116.

Condoluci A, Mazzara C, Zoccoli A, Pezzuto A, Tonini G. Impact of smoking on lung cancer treatment effectiveness: a review. Future Oncol. 2016;12(18):2149–61. https://doi.org/10.2217/fon-2015-0055.CrossRefPubMed

117.

Li B, Huang X, Fu L. Impact of smoking on efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer patients: a meta-analysis. Onco Targets Ther. 2018;11:3691–6. https://doi.org/10.2147/OTT.S156421.CrossRefPubMedPubMedCentral

118.

Lee CK, Man J, Lord S, Cooper W, Links M, Gebski V, et al. Clinical and Molecular Characteristics Associated With Survival Among Patients Treated With Checkpoint Inhibitors for Advanced Non-Small Cell Lung Carcinoma: A Systematic Review and Meta-analysis. JAMA Oncol. 2018;4(2):210–6. https://doi.org/10.1001/jamaoncol.2017.4427.CrossRefPubMed

119.

El-Osta H, Jafri S. Predictors for clinical benefit of immune checkpoint inhibitors in advanced non-small-cell lung cancer: a meta-analysis. Immunotherapy. 2019;11(3):189–99. https://doi.org/10.2217/imt-2018-0086.CrossRefPubMed

120.

Li X, Huang C, Xie X, Wu Z, Tian X, Wu Y, et al. The impact of smoking status on the progression-free survival of non-small cell lung cancer patients receiving molecularly target therapy or immunotherapy versus chemotherapy: A meta-analysis. J Clin Pharm Ther. 2021;46(2):256–66. https://doi.org/10.1111/jcpt.13309.CrossRefPubMed

121.

Kim JH, Kim HS, Kim BJ. Prognostic value of smoking status in non-small-cell lung cancer patients treated with immune checkpoint inhibitors: a meta-analysis. Oncotarget. 2017;8(54):93149–55. https://doi.org/10.18632/oncotarget.18703.

122.

Garassino MC, Gelibter AJ, Grossi F, Chiari R, Soto Parra H, Cascinu S, et al. Italian Nivolumab Expanded Access Program in Nonsquamous Non-Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients. J Thorac Oncol. 2018;13(8):1146–55. https://doi.org/10.1016/j.jtho.2018.04.025.CrossRefPubMed

123.

West H, McCleod M, Hussein M, Morabito A, Rittmeyer A, Conter HJ, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(7):924–37. https://doi.org/10.1016/S1470-2045(19)30167-6.CrossRefPubMed

124.

de Alencar V, Formiga MN, de Lima V. Inherited lung cancer: a review Ecancermedicalscience. 2020;14:1008. https://doi.org/10.3332/ecancer.2020.1008.CrossRefPubMed

125.

Wang GZ, Zhang L, Zhao XC, Gao SH, Qu LW, Yu H, et al. The Aryl hydrocarbon receptor mediates tobacco-induced PD-L1 expression and is associated with response to immunotherapy. Nat Commun. 2019;10(1):1125. https://doi.org/10.1038/s41467-019-08887-7.CrossRefPubMedPubMedCentral

126.

Hu Z, Zheng X, Jiao D, Zhou Y, Sun R, Wang B, et al. LunX-CAR T Cells as a Targeted Therapy for Non-Small Cell Lung Cancer. Mol Ther Oncolytics. 2020;17:361–70. https://doi.org/10.1016/j.omto.2020.04.008.CrossRefPubMedPubMedCentral

127.

Qu J, Mei Q, Chen L, Zhou J. Chimeric antigen receptor (CAR)-T-cell therapy in non-small-cell lung cancer (NSCLC): current status and future perspectives. Cancer Immunol Immunother. 2021;70(3):619–31. https://doi.org/10.1007/s00262-020-02735-0.CrossRefPubMed

128.

Azevedo CR, Cezana L, Moraes ES, Begnami MD, Paiva Júnior TF, Dettino AL, et al. Synchronous thyroid and colon metastases from epidermoid carcinoma of the lung: case report. Sao Paulo Med J. 2010;128(6):371–4. https://doi.org/10.1590/s1516-31802010000600011.CrossRefPubMed

129.

Gibson A, Li H, D’Silva A, Tudor RA, Elegbede AA, Otsuka SM, et al. Impact of number versus location of metastases on survival in stage IV M1b non-small cell lung cancer. Med Oncol. 2018;35(9):117. https://doi.org/10.1007/s12032-018-1182-8.CrossRefPubMed

130.

Ali A, Goffin JR, Arnold A, Ellis PM. Survival of patients with non-small-cell lung cancer after a diagnosis of brain metastases. Curr Oncol. 2013;20(4):e300–6. https://doi.org/10.3747/co.20.1481.CrossRefPubMedPubMedCentral

131.

Ernani V, Stinchcombe TE. Management of Brain Metastases in Non-Small-Cell Lung Cancer. J Oncol Pract. 2019;15(11):563–70. https://doi.org/10.1200/JOP.19.00357.CrossRefPubMedPubMedCentral

132.

Kersten K, Salvagno C, de Visser KE. Exploiting the Immunomodulatory Properties of Chemotherapeutic Drugs to Improve the Success of Cancer Immunotherapy. Front Immunol. 2015;6:516. https://doi.org/10.3389/fimmu.2015.00516.CrossRefPubMedPubMedCentral

133.

Peng J, Hamanishi J, Matsumura N, Abiko K, Murat K, Baba T, et al. Chemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-κB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer. Cancer Res. 2015;75(23):5034–45. https://doi.org/10.1158/0008-5472.CAN-14-3098.CrossRefPubMed

134.

Wang Z, Till B, Gao Q. Chemotherapeutic agent-mediated elimination of myeloid-derived suppressor cells. Oncoimmunology. 2017;6(7):e1331807. https://doi.org/10.1080/2162402X.2017.1331807.

135.

Afzal MZ, Dragnev K, Shirai K. A tertiary care cancer center experience with carboplatin and pemetrexed in combination with pembrolizumab in comparison with carboplatin and pemetrexed alone in non-squamous non-small cell lung cancer. J Thorac Dis. 2018;10(6):3575–84. https://doi.org/10.21037/jtd.2018.06.08.

136.

Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation immunotherapy–inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res. 2012;18(24):6580–7. https://doi.org/10.1158/1078-0432.CCR-12-1362.CrossRefPubMed

137.

Soria JC, Marabelle A, Brahmer JR, Gettinger S. Immune checkpoint modulation for non-small cell lung cancer. Clin Cancer Res. 2015;21(10):2256–62. https://doi.org/10.1158/1078-0432.CCR-14-2959.CrossRefPubMed

138.

Buchbinder EI, Desai A. CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition. Am J Clin Oncol. 2016;39(1):98–106. https://doi.org/10.1097/COC.0000000000000239.CrossRefPubMedPubMedCentral

139.

Chen YB, Mu CY, Huang JA. 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(6):751–5. https://doi.org/10.1700/1217.13499.CrossRefPubMed

140.

D’Incecco A, Andreozzi M, Ludovini V, Rossi E, Capodanno A, Landi L, et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 2015;112(1):95–102. https://doi.org/10.1038/bjc.2014.555.CrossRefPubMed

141.

Cha YJ, Kim HR, Lee CY, Cho BC, Shim HS. Clinicopathological and prognostic significance of programmed cell death ligand-1 expression in lung adenocarcinoma and its relationship with p53 status. Lung Cancer. 2016;97:73–80. https://doi.org/10.1016/j.lungcan.2016.05.001.CrossRefPubMed

142.

Takada K, Okamoto T, Shoji F, Shimokawa M, Akamine T, Takamori S, et al. Clinical Significance of PD-L1 Protein Expression in Surgically Resected Primary Lung Adenocarcinoma. J Thorac Oncol. 2016;11(11):1879–90. https://doi.org/10.1016/j.jtho.2016.06.006.CrossRefPubMed

143.

Li H, Xu Y, Wan B, Song Y, Zhan P, Hu Y, et al. The clinicopathological and prognostic significance of PD-L1 expression assessed by immunohistochemistry in lung cancer: a meta-analysis of 50 studies with 11,383 patients. Transl Lung Cancer Res. 2019;8(4):429–49. https://doi.org/10.21037/tlcr.2019.08.04.

144.

Tuminello S, Sikavi D, Veluswamy R, Gamarra C, Lieberman-Cribbin W, Flores R, et al. PD-L1 as a prognostic biomarker in surgically resectable non-small cell lung cancer: a meta-analysis. Transl Lung Cancer Res. 2020;9(4):1343–60. https://doi.org/10.21037/tlcr-19-638.

145.

Majem M, Cobo M, Isla D, Marquez-Medina D, Rodriguez-Abreu D, Casal-Rubio J, et al. PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis. J Clin Med. 2021;10(7). https://doi.org/10.3390/jcm10071365.

146.

Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021;39(21):2339–49. https://doi.org/10.1200/JCO.21.00174.CrossRefPubMedPubMedCentral

147.

Rozeman EA, Menzies AM, van Akkooi A, Adhikari C, Bierman C, van de Wiel BA, et al. Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial. Lancet Oncol. 2019;20(7):948–60. https://doi.org/10.1016/S1470-2045(19)30151-2.CrossRefPubMed

148.

Haanen JB, Blank CU. Prognostic and predictive role of the tumor immune landscape. Q J Nucl Med Mol Imaging. 2020;64(2):143–51. https://doi.org/10.23736/S1824-4785.20.03255-0.

Title: Clinical benefit of pembrolizumab in treatment of first line non-small cell lung cancer: a systematic review and meta-analysis of clinical characteristics
Authors: Wenjie Liu
Gengwei Huo
Peng Chen
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: NSCLC
NSCLC
Cytostatic Therapy
Published in: BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-023-10959-3

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Image Credits

ASCO 2024 | Highlights of the Day: Breast cancer – metastatic/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Gynecologic Cancer/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Breast Cancer – local/regional/adjuvant/© 2024 American Society of Clinical Oncology, all rights reserved., Melanoma/© selvanegra / Getty Images / iStock, Antibody drug conjugated with cytotoxic payload/© Love Employee / Getty images / iStock

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2023

Clinical characteristics and prognostic characterization of endometrial carcinoma: a comparative analysis of molecular typing protocols

Pan-cancer analysis identifies SPEN mutation as a predictive biomarker with the efficacy of immunotherapy

Association between insulin resistance and cardiac remodeling in HER2-positive breast cancer patients: a real-world study

Association between metabolic syndrome and early-stage colorectal cancer

The impact of sarcopenia on the outcome of patients with left-sided colon and rectal cancer after curative surgery