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Original article

Vol. 153 No. 1 (2023)

Overall survival and role of programmed death ligand 1 expression in patients with metastatic non-small-cell lung cancer and immunotherapy: an observational study from central Switzerland

  • Valentina Allmann
  • Daniela Dyntar
  • Dirk Lehnick
  • Marco Dressler
  • Kristin Zeidler
  • Philipp Niederberger
  • Jeanne Godau
  • Joachim Diebold
  • Oliver Gautschi
DOI
https://doi.org/10.57187/smw.2023.40039
Cite this as:
Swiss Med Wkly. 2023;153:40039
Published
30.01.2023

Summary

BACKGROUND: In clinical trials, therapy with immune checkpoint inhibitors has improved the survival of patients with metastatic non-small-cell lung cancer (NSCLC). These trials were important for drug approval and for defining new treatment standards but the effect of checkpoint inhibitors in patients treated outside of clinical trials is not well known. The goal of this study was to assess the effect of immunotherapy on the overall survival of patients with metastatic NSCLC in the region of central Switzerland.

MATERIALS AND METHODS: The study included 274 patients with histologically confirmed metastatic (stage IV) NSCLC in central Switzerland in the years 2015 to 2018. Patients with NSCLC and actionable driver mutations were excluded. Patients with checkpoint inhibitor treatment (immuno-oncology [IO] group, n = 122) were compared with patients without checkpoint inhibitor treatment (no-IO group, n = 152). Baseline demographics, disease characteristics and therapies applied were collected retrospectively. The primary endpoint was median overall survival calculated either from diagnosis or from the start of checkpoint inhibitor therapy to death or data cut-off (21 July 2021). We used the Kaplan-Meier method and an adjusted Cox proportional-hazards regression model. The expression of programmed-death ligand 1 (PD-L1) on tumour cells was used for exploratory analysis.

RESULTS: Patients had a median age of 68.4 years, most were male (61.7%) and more than half were current or former smokers (65%). A test for PD-L1 expression was available for 55.8% of the tumours. Patients in the IO group were younger than patients in the no-IO group. Among the 122 patients in the IO group, the median overall survival was 15 months (95% confidence interval [CI] 12–20). In the no-IO group, the median overall survival was 4 months (95% CI 3–7) with chemotherapy and 2 months (95% CI 1–2) with best supportive care. Patients with high (≥50%) PD-L1 expression and checkpoint inhibitor therapy had a slightly longer overall survival than patients with low PD-L1 and checkpoint inhibitor therapy.

CONCLUSION: These results suggest that treatment with checkpoint inhibitors improves overall survival in patients with metastatic NSCLC and that PD-L1 expression could have a predictive value in patients treated outside of clinical trials. Further studies are needed to study the magnitude of the benefit of checkpoint inhibitors according to molecular NSCLC subtype.

References

  1. Godtfredsen NS, Prescott E, Osler M. Effect of smoking reduction on lung cancer risk. JAMA. 2005 Sep;294(12):1505–10. https://doi.org/10.1001/jama.294.12.1505
  2. Doll R, Hill AB. Smoking and carcinoma of the lung; preliminary report. BMJ. 1950 Sep;2(4682):739–48. https://doi.org/10.1136/bmj.2.4682.739
  3. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013 Apr;49(6):1374–403. https://doi.org/10.1016/j.ejca.2012.12.027
  4. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394–424. https://doi.org/10.3322/caac.21492
  5. Gmel G. K.H., Notari L, Gmel C. Suchtmonitoring Schweiz - Konsum von Alkohol, Tabak und illegalen Drogen in der Schweiz im Jahr 2016. Lausanne, Schweiz: Sucht Schweiz; 2017.
  6. Pasquale., C., et al., Schweizerischer Krebsbericht 2021. Schweizerischer Krebsbericht. 2021: Bundesamt für Statistik (BFS), Nationale Krebsregistrierungsstelle (NKRS). 57-61.
  7. Casutt A, Lovis A, Selby K, Noirez L, Peters S, Beigelman-Aubry C, et al. [Lung cancer screening in Switzerland : Who? How? When? ]. Rev Med Suisse. 2020 Nov;16(715):2224–6. https://doi.org/10.53738/REVMED.2020.16.715.2224
  8. Chen, V.W., et al., Analysis of stage and clinical/prognostic factors for lung cancer from SEER registries: AJCC staging and collaborative stage data collection system. Cancer, 2014. 120 Suppl 23(0 0): p. 3781-92 DOI: https://doi.org/10.1002/cncr.29045.
  9. NSCLC Meta-Analyses Collaborative Group. Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. J Clin Oncol. 2008 Oct;26(28):4617–25. https://doi.org/10.1200/jco.2008.17.7162
  10. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul;373(2):123–35. https://doi.org/10.1056/NEJMoa1504627
  11. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct;373(17):1627–39. https://doi.org/10.1056/NEJMoa1507643
  12. Ganz PA, Figlin RA, Haskell CM, La Soto N, Siau J. Supportive care versus supportive care and combination chemotherapy in metastatic non-small cell lung cancer. Does chemotherapy make a difference? Cancer. 1989 Apr;63(7):1271–8. https://doi.org/10.1002/1097-0142
  13. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58(2):71–96. https://doi.org/10.3322/ca.2007.0010
  14. Novello S, Barlesi F, Califano R, Cufer T, Ekman S, Levra MG, et al.; ESMO Guidelines Committee. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016 Sep;27 suppl 5:v1–27. https://doi.org/10.1093/annonc/mdw326
  15. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep;361(10):947–57. https://doi.org/10.1056/NEJMoa0810699
  16. Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, et al.; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014 Dec;371(23):2167–77. https://doi.org/10.1056/NEJMoa1408440
  17. Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, et al.; ALEX Trial Investigators. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Aug;377(9):829–38. https://doi.org/10.1056/NEJMoa1704795
  18. Passaro A, Attili I, Morganti S, Del Signore E, Gianoncelli L, Spitaleri G, et al. Clinical features affecting survival in metastatic NSCLC treated with immunotherapy: A critical review of published data. Cancer Treat Rev. 2020 Sep;89:102085. https://doi.org/10.1016/j.ctrv.2020.102085
  19. Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 2015 Aug;5(9):2892–911.
  20. Hirsch FR, Suda K, Wiens J, Bunn PA Jr. New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 2016 Sep;388(10048):1012–24. https://doi.org/10.1016/S0140-6736(16)31473-8
  21. Grant MJ, Herbst RS, Goldberg SB. Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC. Nat Rev Clin Oncol. 2021 Oct;18(10):625–44. https://doi.org/10.1038/s41571-021-00520-1
  22. Aisner DL, Marshall CB. Molecular pathology of non-small cell lung cancer: a practical guide. Am J Clin Pathol. 2012 Sep;138(3):332–46. https://doi.org/10.1309/ajcpfr12wjkceezz
  23. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al.; OAK Study Group. 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 Jan;389(10066):255–65. https://doi.org/10.1016/s0140-6736(16)32517-x
  24. Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, et al.; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr;387(10030):1837–46. https://doi.org/10.1016/s0140-6736(16)00587-0
  25. 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 Apr;387(10027):1540–50. https://doi.org/10.1016/S0140-6736(15)01281-7
  26. 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 Jul;39(21):2339–49. https://doi.org/10.1200/JCO.21.00174
  27. 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 May;38(14):1505–17. https://doi.org/10.1200/jco.19.03136
  28. Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al.; KEYNOTE-189 Investigators. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018 May;378(22):2078–92. https://doi.org/10.1056/NEJMoa1801005
  29. Addeo A, Passaro A, Malapelle U, Banna GL, Subbiah V, Friedlaender A. Immunotherapy in non-small cell lung cancer harbouring driver mutations. Cancer Treat Rev. 2021 May;96:102179. https://doi.org/10.1016/j.ctrv.2021.102179
  30. Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, et al.; IMpower150 Study Group. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018 Jun;378(24):2288–301. https://doi.org/10.1056/NEJMoa1716948
  31. Socinski MA, Nishio M, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, et al. IMpower150 Final Overall Survival Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in First-Line Metastatic Nonsquamous NSCLC. J Thorac Oncol. 2021 Nov;16(11):1909–24. https://doi.org/10.1016/j.jtho.2021.07.009
  32. Reck M, Rabe KF. Precision Diagnosis and Treatment for Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Aug;377(9):849–61. https://doi.org/10.1056/NEJMra1703413
  33. Al-Baimani K, Jonker H, Zhang T, Goss GD, Laurie SA, Nicholas G, et al. Are clinical trial eligibility criteria an accurate reflection of a real-world population of advanced non-small-cell lung cancer patients? Curr Oncol. 2018 Aug;25(4):e291–7. https://doi.org/10.3747/co.25.3978
  34. Pasello G, Pavan A, Attili I, Bortolami A, Bonanno L, Menis J, et al. Real world data in the era of Immune Checkpoint Inhibitors (ICIs): increasing evidence and future applications in lung cancer. Cancer Treat Rev. 2020 Jul;87:102031. https://doi.org/10.1016/j.ctrv.2020.102031
  35. Spigel DR, McCleod M, Jotte RM, Einhorn L, Horn L, Waterhouse DM, et al. Safety, Efficacy, and Patient-Reported Health-Related Quality of Life and Symptom Burden with Nivolumab in Patients with Advanced Non-Small Cell Lung Cancer, Including Patients Aged 70 Years or Older or with Poor Performance Status (CheckMate 153). J Thorac Oncol. 2019 Sep;14(9):1628–39. https://doi.org/10.1016/j.jtho.2019.05.010
  36. Andreano A, Bergamaschi W, Russo AG. Immune checkpoint inhibitors at any treatment line in advanced NSCLC: real-world overall survival in a large Italian cohort. Lung Cancer. 2021 Sep;159:145–52. https://doi.org/10.1016/j.lungcan.2021.06.019
  37. Schwegler C, Kaufmann D, Pfeiffer D, Aebi S, Diebold J, Gautschi O. Population-level effect of molecular testing and targeted therapy in patients with advanced pulmonary adenocarcinoma: a prospective cohort study. Virchows Arch. 2018 Apr;472(4):581–8. https://doi.org/10.1007/s00428-017-2268-y
  38. Cancer Registry of Central Switzerland. Available from: https://www.zentralschweizer-krebsregister.ch/
  39. Organization chart (LUKS). Available from: https://www.luks.ch/ihr-luks/organisation
  40. History of the Cantonal Hospital of Lucerne. Available from: https://www.luks.ch/informationen-fuer-besuchende/geschichte-des-luzerner-kantonsspitals
  41. Lee CK, Brown C, Gralla RJ, Hirsh V, Thongprasert S, Tsai CM, et al. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst. 2013 May;105(9):595–605. https://doi.org/10.1093/jnci/djt072
  42. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007 Oct;370(9596):1453–7. https://doi.org/10.1016/S0140-6736(07)61602-X
  43. WHO Organization The ICD-10 classification of mental and behavioural disorders, Version 2019. Geneva, Switzerland: World Health Organization; 1993.
  44. StataCorp LLC, College Station, Texas, USA. Available from: https://www.stata.com/support/faqs/resources/citing-software-documentation-faqs/
  45. Ryser CO, Gautschi O, Diebold J. Bronchialkarzinom - Neue Ansätze in der Therapie. Info Onkologie & Hämatologie 201912–7
  46. Bodor JN, Boumber Y, Borghaei H. Biomarkers for immune checkpoint inhibition in non-small cell lung cancer (NSCLC). Cancer. 2020 Jan;126(2):260–70. https://doi.org/10.1002/cncr.32468
  47. Sacher AG, Gandhi L. Biomarkers for the Clinical Use of PD-1/PD-L1 Inhibitors in Non-Small-Cell Lung Cancer: A Review. JAMA Oncol. 2016 Sep;2(9):1217–22. https://doi.org/10.1001/jamaoncol.2016.0639
  48. Ivanović M, Knez L, Herzog A, Kovačević M, Cufer T. Immunotherapy for Metastatic Non-Small Cell Lung Cancer: Real-World Data from an Academic Central and Eastern European Center. Oncologist. 2021 Dec;26(12):e2143–50. https://doi.org/10.1002/onco.13909
  49. Wallrabenstein T, Del Rio J, Templeton AJ, Buess M. Much has changed in the last decade except overall survival: A Swiss single center analysis of treatment and survival in patients with stage IV non-small cell lung cancer. PLoS One. 2020 May;15(5):e0233768. https://doi.org/10.1371/journal.pone.0233768
  50. Alonso-García M, Sánchez-Gastaldo A, Muñoz-Fuentes MA, Molina-Pinelo S, Boyero L, Benedetti JC, et al. Real-World Analysis of Nivolumab and Atezolizumab Efficacy in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer. Pharmaceuticals (Basel). 2022 Apr;15(5):533. https://doi.org/10.3390/ph15050533
  51. Figueiredo A, Almeida MA, Almodovar MT, Alves P, Araújo A, Araújo D, et al. Real-world data from the Portuguese Nivolumab Expanded Access Program (EAP) in previously treated Non Small Cell Lung Cancer (NSCLC). Pulmonology. 2020;26(1):10–7. https://doi.org/10.1016/j.pulmoe.2019.06.001
  52. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al.; KEYNOTE-024 Investigators. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov;375(19):1823–33. https://doi.org/10.1056/NEJMoa1606774
  53. 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 Mar;37(7):537–46. https://doi.org/10.1200/jco.18.00149
  54. Mok TS, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, et al.; KEYNOTE-042 Investigators. 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 May;393(10183):1819–30. https://doi.org/10.1016/S0140-6736(18)32409-7
  55. Paz-Ares L, Vicente D, Tafreshi A, Robinson A, Soto Parra H, Mazières J, et al. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. J Thorac Oncol. 2020 Oct;15(10):1657–69. https://doi.org/10.1016/j.jtho.2020.06.015
  56. Jassem J, et al. IMpower110: Clinical safety in a phase III study of atezolizumab (atezo) monotherapy (mono) vs platinum-based chemotherapy (chemo) in first-line non-small cell lung cancer (NSCLC). American Society of Clinical Oncology; 2020.
  57. 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 Jul;20(7):924–37. https://doi.org/10.1016/S1470-2045(19)30167-6
  58. 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 May;38(14):1580–90. https://doi.org/10.1200/JCO.19.02446
  59. Naylor K, Li G, Vallejo AN, Lee WW, Koetz K, Bryl E, et al. The influence of age on T cell generation and TCR diversity. J Immunol. 2005 Jun;174(11):7446–52. https://doi.org/10.4049/jimmunol.174.11.7446
  60. Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, et al.; ESMO Guidelines Committee. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct;29 Suppl 4:iv192–237. https://doi.org/10.1093/annonc/mdy275
  61. Kawaguchi T, Takada M, Kubo A, Matsumura A, Fukai S, Tamura A, et al. Performance status and smoking status are independent favorable prognostic factors for survival in non-small cell lung cancer: a comprehensive analysis of 26,957 patients with NSCLC. J Thorac Oncol. 2010 May;5(5):620–30. https://doi.org/10.1097/JTO.0b013e3181d2dcd9
  62. Simmons CP, Koinis F, Fallon MT, Fearon KC, Bowden J, Solheim TS, et al. Prognosis in advanced lung cancer—A prospective study examining key clinicopathological factors. Lung Cancer. 2015 Jun;88(3):304–9. https://doi.org/10.1016/j.lungcan.2015.03.020
  63. Socinski MA, et al. Treatment of Non-small Cell Lung Cancer, Stage IV: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition). Chest, 2007. 132(3, Supplement): p. 277S-289S DOI: https://doi.org/https://doi.org/10.1378/chest.07-1381
  64. Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, et al. Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017 Dec;35(35):3924–33. https://doi.org/10.1200/JCO.2017.74.3062
  65. Peters S, Danson S, Hasan B, Dafni U, Reinmuth N, Majem M, et al. A Randomized Open-Label Phase III Trial Evaluating the Addition of Denosumab to Standard First-Line Treatment in Advanced NSCLC: The European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR Trial. J Thorac Oncol. 2020 Oct;15(10):1647–56. https://doi.org/10.1016/j.jtho.2020.06.011
  66. Cramer-van der Welle CM, Verschueren MV, Tonn M, Peters BJ, Schramel FM, Klungel OH, et al.; Santeon NSCLC Study Group. Real-world outcomes versus clinical trial results of immunotherapy in stage IV non-small cell lung cancer (NSCLC) in the Netherlands. Sci Rep. 2021 Mar;11(1):6306. https://doi.org/10.1038/s41598-021-85696-3
  67. Bittoni MA, Arunachalam A, Li H, Camacho R, He J, Zhong Y, et al. Real-World Treatment Patterns, Overall Survival, and Occurrence and Costs of Adverse Events Associated With First-line Therapies for Medicare Patients 65 Years and Older With Advanced Non-small-cell Lung Cancer: A Retrospective Study. Clin Lung Cancer. 2018 Sep;19(5):e629–45. https://doi.org/10.1016/j.cllc.2018.04.017
  68. Seung SJ, Hurry M, Walton RN, Evans WK. Real-world treatment patterns and survival in stage IV non-small-cell lung cancer in Canada. Curr Oncol. 2020 Aug;27(4):e361–7. https://doi.org/10.3747/co.27.6049
  69. Dearden S, Stevens J, Wu YL, Blowers D. Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap). Ann Oncol. 2013 Sep;24(9):2371–6. https://doi.org/10.1093/annonc/mdt205
  70. Ruiz-Patiño A, Rodríguez J, Cardona AF, Ávila J, Archila P, Carranza H, et al.; ONCOLGroup; CLICaP. p.G12C KRAS mutation prevalence in non-small cell lung cancer: contribution from interregional variability and population substructures among Hispanics. Transl Oncol. 2022 Jan;15(1):101276. https://doi.org/10.1016/j.tranon.2021.101276
  71. Goulding RE, Chenoweth M, Carter GC, Boye ME, Sheffield KM, John WJ, et al. KRAS mutation as a prognostic factor and predictive factor in advanced/metastatic non-small cell lung cancer: A systematic literature review and meta-analysis. Cancer Treat Res Commun. 2020;24:100200. https://doi.org/10.1016/j.ctarc.2020.100200
  72. Cefalì M, Epistolio S, Ramelli G, Mangan D, Molinari F, Martin V, et al. Correlation of KRAS G12C Mutation and High PD-L1 Expression with Clinical Outcome in NSCLC Patients Treated with Anti-PD1 Immunotherapy. J Clin Med. 2022 Mar;11(6):1627. https://doi.org/10.3390/jcm11061627
  73. Landre T, Justeau G, Assié JB, Chouahnia K, Davoine C, Taleb C, et al. Anti-PD-(L)1 for KRAS-mutant advanced non-small-cell lung cancers: a meta-analysis of randomized-controlled trials. Cancer Immunol Immunother. 2022 Mar;71(3):719–26. https://doi.org/10.1007/s00262-021-03031-1
  74. Dong ZY, Zhong WZ, Zhang XC, Su J, Xie Z, Liu SY, et al. Potential predictive value of TP53 and KRAS mutation status for response to PD-1 blockade immunotherapy in lung adenocarcinoma. Clin Cancer Res. 2017 Jun;23(12):3012–24. https://doi.org/10.1158/1078-0432.CCR-16-2554
  75. Arbour KC, Jordan E, Kim HR, Dienstag J, Yu HA, Sanchez-Vega F, et al. Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2018 Jan;24(2):334–40. https://doi.org/10.1158/1078-0432.CCR-17-1841
  76. Biton J, Mansuet-Lupo A, Pécuchet N, Alifano M, Ouakrim H, Arrondeau J, et al. TP53, STK11, and EGFR Mutations Predict Tumor Immune Profile and the Response to Anti-PD-1 in Lung Adenocarcinoma. Clin Cancer Res. 2018 Nov;24(22):5710–23. https://doi.org/10.1158/1078-0432.CCR-18-0163
  77. Yu Y, Zeng D, Ou Q, Liu S, Li A, Chen Y, et al. Association of survival and immune-related biomarkers with immunotherapy in patients with non–small cell lung cancer: A meta-analysis and individual patient–level analysis. JAMA Netw Open. 2019 Jul;2(7):e196879–196879. https://doi.org/10.1001/jamanetworkopen.2019.6879
  78. Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, et al. Sotorasib for lung cancers with KRAS p. G12C mutation. N Engl J Med. 2021 Jun;384(25):2371–81. https://doi.org/10.1056/NEJMoa2103695
  79. Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217–23. https://doi.org/10.1038/s41586-019-1694-1
  80. Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, et al. KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020 Sep;383(13):1207–17. https://doi.org/10.1056/NEJMoa1917239

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