Efficacy and safety analysis of immune checkpoint inhibitors in the first-line treatment of patients with advanced NSCLC: A systematic evaluation and meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LUO Xindong ¹ ,  GOU Yunjiu ² , ZENG Weiqiang ² , JIN Dacheng ² , CUI Baiqiang ²

1. The First Clinical Department of Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, P. R. China;
2. Department of Thoracic Surgery, Gansu Provincial Hospital, Lanzhou, 730000, P. R. China;

Corresponding author：

GOU Yunjiu, Email: gouyunjiu@163.com

Keywords：

Immune checkpoint inhibitors; first-line therapy; non-small cell lung cancer; efficacy; safety; systematic evaluation/meta-analysis

DOI：

10.7507/1007-4848.202304014

Video：

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Objective To systematically review the efficacy and safety of immune checkpoint inhibitors (ICIs) as first-line treatment for advanced non-small cell lung cancer (NSCLC). Methods To collect clinical randomized controlled trials of ICIs for the first-line treatment of patients with NSCLC, computer searches were conducted on PubMed, The Cochrane Library, and EMbase databases. The search time frame was inception to January 2023. A meta-analysis was performed using Revman 5.4 software. Results Twelve clinical studies were included, all of which were assessed as high-quality literature with a total of 7 121 patients. Meta-analysis showed that the first-line treatment of NSCLC patients with ICIs significantly improved median overall survival (OS) (HR=0.72, 95%CI 0.64 to 0.80, P < 0.000 01), prolonged median progression-free survival (PFS) (HR=0.65, 95%CI 0.53 to 0.78, P<0.000 01), and improved objective response rate (ORR) (RR=1.52, 95%CI 1.28 to 1.79, P<0.000 01), compared to chemotherapy. Subgroup analysis showed that the ICIs combination therapy group significantly improved OS, PFS, and ORR in NSCLC patients compared to the ICIs monotherapy group. In terms of safety, the ICIs group had a lower risk of treatment-related adverse events (TRAEs) of any grade and grade 3-5 TRAEs than the chemotherapy group. However, the ICIs group had a higher incidence of TRAEs leading to treatment cessation than the chemotherapy group. Subgroup analysis showed that the incidence of any grade TRAEs, grade 3-5 TRAEs, leading to treatment discontinuation TRAEs was higher in the immune combination therapy group than in the immune monotherapy group. Conclusion The first-line treatment of NSCLC patients with ICIs inhibitors significantly improved OS, PFS, and ORR compared to chemotherapy. Immune-combination chemotherapy significantly improved the outcomes of NSCLC patients, compared to immune monotherapy, but patients were at a higher risk of TRAEs.

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2.	Travis WD. Pathology of lung cancer. Clin Chest Med, 2011, 32(4): 669-692.
3.	Wang MC, Liang X, Liu ZY, et al. In vitro synergistic antitumor efficacy of sequentially combined chemotherapy/icotinib in non-small cell lung cancer cell lines. Oncol Rep, 2015, 33(1): 239-249.
4.	Rossi A, Di Maio M. Platinum-based chemotherapy in advanced non-small-cell lung cancer: Optimal number of treatment cycles. Expert Rev Anticancer Ther, 2016, 16(6): 653-660.
5.	Khunger M, Jain P, Rakshit S, et al. Safety and efficacy of PD-1/PD-L1 inhibitors in treatment-naive and chemotherapy-refractory patients with non-small-cell lung cancer: A systematic review and meta-analysis. Clin Lung Cancer, 2018, 19(3): e335-e348.335-348.
6.	Pharaon R, Koczywas MA, Salgia S, et al. Biomarkers in immunotherapy: Literature review and future directions. J Thorac Dis, 2020, 12(9): 5119-5127.
7.	Reck M, Rodríguez-Abreu D, Robinson AG, 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): 537-546.
8.	Wu YL, Lu S, Cheng Y, et al. Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced NSCLC: CheckMate 078 randomized phase Ⅲ clinical trial. J Thorac Oncol, 2019, 14(5): 867-875.
9.	Hida T, Kaji R, Satouchi M, et al. Atezolizumab in Japanese patients with previously treated advanced non-small-cell lung cancer: A subgroup analysis of the phase 3 OAK study. Clin Lung Cancer, 2018, 19(4): e405-e415.
10.	Barlesi F, Vansteenkiste J, Spigel D, et al. Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): An open-label, randomised, phase 3 study. Lancet Oncol, 2018, 19(11): 1468-1479.
11.	Park K, Özgüroğlu M, Vansteenkiste J, et al. Avelumab versus docetaxel in patients with platinum-treated advanced NSCLC: 2-year follow-up from the JAVELIN lung 200 phase 3 trial. J Thorac Oncol, 2021, 16(8): 1369-1378.
12.	Sezer A, Kilickap S, Gümüş M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: A multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet, 2021, 397(10274): 592-604.
13.	Zhou C, Chen G, Huang Y, et al. Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): A randomised, open-label, multicentre, phase 3 trial. Lancet Respir Med, 2021, 9(3): 305-314.
14.	Reck M, Rodríguez-Abreu D, Robinson AG, 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): 2339-2349.
15.	Carbone DP, Reck M, Paz-Ares L, et al. First-line nivolumab in stage Ⅳ or recurrent non-small-cell lung cancer. N Engl J Med, 2017, 376(25): 2415-2426.
16.	de Castro G, Kudaba I, Wu YL, et al. Five-year outcomes with pembrolizumab versus chemotherapy as first-line therapy in patients with non-small-cell lung cancer and programmed death ligand-1 tumor proportion score≥1% in the KEYNOTE-042 study. J Clin Oncol, 2023, 41(11): 1986-1991.
17.	Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med, 2020, 383(14): 1328-1339.
18.	Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med, 2018, 378(22): 2078-2092.
19.	West H, McCleod M, Hussein M, 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): 924-937.
20.	Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): An international, randomised, open-label, phase 3 trial. Lancet Oncol, 2021, 22(2): 198-211.
21.	Gogishvili M, Melkadze T, Makharadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: A randomized, controlled, double-blind phase 3 trial. Nat Med, 2022, 28(11): 2374-2380.
22.	Paz-Ares LG, Ramalingam SS, Ciuleanu TE, et al. First-line nivolumab plus ipilimumab in advanced nsclC: 4-year outcomes from the randomized, open-label, phase 3 CheckMate 227 part 1 trial. J Thorac Oncol, 2022, 17(2): 289-308.
23.	Ren S, Chen J, Xu X, et al. Camrelizumab plus carboplatin and paclitaxel as first-line treatment for advanced squamous NSCLC (CameL-Sq): A phase 3 trial. J Thorac Oncol, 2022, 17(4): 544-557.
24.	Zhou C, Wang Z, Sun Y, et al. Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): Interim and final analyses of a double-blind, randomised, phase 3 clinical trial. Lancet Oncol, 2022, 23(2): 220-233.
25.	Cheng TY, Cramb SM, Baade PD, et al. The international epidemiology of lung cancer: Latest trends, disparities, and tumor characteristics. J Thorac Oncol, 2016, 11(10): 1653-1671.
26.	Cetin K, Ettinger DS, Hei YJ, et al. Survival by histologic subtype in stageⅣ nonsmall cell lung cancer based on data from the Surveillance, Epidemiology and End Results Program. Clin Epidemiol, 2011, 3: 139-148.
27.	Najafi M, Farhood B, Mortezaee K. Contribution of regulatory T cells to cancer: A review. J Cell Physiol, 2019, 234(6): 7983-7993.
28.	Vinay DS, Ryan EP, Pawelec G, et al. Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Seminars in cancer biology. Academic Press, 2015, 35: S185-S198.
29.	Abdel-Rahman O. Immune checkpoints aberrations and gastric cancer; assessment of prognostic value and evaluation of therapeutic potentials. Crit Rev Oncol Hematol, 2016, 97: 65-71.
30.	Shimanovsky A, Dasanu CA. Updates on immunotherapy in non-small cell lung cancer. Expert Opin Biol Ther, 2014, 14(4): 411-418.
31.	Sznol M, Chen L. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res, 2013, 19(5): 1021-1034.
32.	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(8): 793-800.
33.	Kim DH, Kim H, Choi YJ, et al. Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer. Exp Mol Med, 2019, 51(8): 1-13.
34.	Ribas A. Releasing the brakes on cancer immunotherapy. N Engl J Med, 2015, 373(16): 1490-1492.
35.	Brito ABC, Camandaroba MPG, de Lima VCC. Anti-PD1 versus anti-PD-L1 immunotherapy in first-line therapy for advanced non-small cell lung cancer: A systematic review and meta-analysis. Thorac Cancer, 2021, 12(7): 1058-1066.
36.	Zeng T, Qin Q, Bian Z, et al. Clinical efficacy and safety of anti-PD-1/PD-L1 treatments in non-small cell lung cancer (NSCLC). Artif Cells Nanomed Biotechnol, 2019, 47(1): 4194-4201.
37.	Tran L, Allen CT, Xiao R, et al. Cisplatin alters antitumor immunity and synergizes with PD-1/PD-L1 inhibition in head and neck squamous cell carcinoma. Cancer Immunol Res, 2017, 5(12): 1141-1151.
38.	Fournel L, Wu Z, Stadler N, et al. Cisplatin increases PD-L1 expression and optimizes immune check-point blockade in non-small cell lung cancer. Cancer Lett, 2019, 464: 5-14.
39.	Ready N, Hellmann MD, Awad MM, et al. First-line nivolumab plus ipilimumab in advanced non-small-cell lung cancer (CheckMate 568): Outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers. J Clin Oncol, 2019, 37(12): 992-1000.
40.	Jansen JP, Fleurence R, Devine B, et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: Report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: Part 1. Value Health, 2011, 14(4): 417-428.
41.	Nishio M, Takahashi T, Yoshioka H, et al. KEYNOTE-025: Phase 1b study of pembrolizumab in Japanese patients with previously treated programmed death ligand 1-positive advanced non-small-cell lung cancer. Cancer Sci, 2019, 110(3): 1012-1020.
42.	Leighl NB, Hellmann MD, Hui R, et al. Pembrolizumab in patients with advanced non-small-cell lung cancer (KEYNOTE-001): 3-year results from an open-label, phase 1 study. Lancet Respir Med, 2019, 7(4): 347-357.
43.	Li ZQ, Yan HC, Gu JJ, et al. Comparative efficacy and safety of PD-1/PD-L1 Inhibitors versus platinum-based chemotherapy for the first-line treatment of advanced non-small cell lung cancer: A meta analysis of randomized controlled trials. Pharmacol Res, 2020, 160: 105194.
44.	Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial. Lancet, 2021, 398(10294): 27-40.
45.	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, 2015, 16(4): 375-384.
46.	Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med, 2015, 372(26): 2521-2532.
47.	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(2): 123-135.
48.	Weber JS, Yang JC, Atkins MB, et al. Toxicities of immunotherapy for the practitioner. J Clin Oncol, 2015, 33(18): 2092-2099.
49.	Ribas A, Kefford R, Marshall MA, et al. Phase Ⅲ randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol, 2013, 31(5): 616-622.
50.	Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med, 2010, 363(8): 711-723.
51.	Alissafi T, Hatzioannou A, Legaki AI, et al. Balancing cancer immunotherapy and immune-related adverse events: The emerging role of regulatory T cells. J Autoimmun, 2019, 104: 102310.
52.	Naidoo J, Page DB, Li BT, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol, 2015, 26(12): 2375-2391.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Travis WD. Pathology of lung cancer. Clin Chest Med, 2011, 32(4): 669-692.
3. Wang MC, Liang X, Liu ZY, et al. In vitro synergistic antitumor efficacy of sequentially combined chemotherapy/icotinib in non-small cell lung cancer cell lines. Oncol Rep, 2015, 33(1): 239-249.
4. Rossi A, Di Maio M. Platinum-based chemotherapy in advanced non-small-cell lung cancer: Optimal number of treatment cycles. Expert Rev Anticancer Ther, 2016, 16(6): 653-660.
5. Khunger M, Jain P, Rakshit S, et al. Safety and efficacy of PD-1/PD-L1 inhibitors in treatment-naive and chemotherapy-refractory patients with non-small-cell lung cancer: A systematic review and meta-analysis. Clin Lung Cancer, 2018, 19(3): e335-e348.335-348.
6. Pharaon R, Koczywas MA, Salgia S, et al. Biomarkers in immunotherapy: Literature review and future directions. J Thorac Dis, 2020, 12(9): 5119-5127.
7. Reck M, Rodríguez-Abreu D, Robinson AG, 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): 537-546.
8. Wu YL, Lu S, Cheng Y, et al. Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced NSCLC: CheckMate 078 randomized phase Ⅲ clinical trial. J Thorac Oncol, 2019, 14(5): 867-875.
9. Hida T, Kaji R, Satouchi M, et al. Atezolizumab in Japanese patients with previously treated advanced non-small-cell lung cancer: A subgroup analysis of the phase 3 OAK study. Clin Lung Cancer, 2018, 19(4): e405-e415.
10. Barlesi F, Vansteenkiste J, Spigel D, et al. Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): An open-label, randomised, phase 3 study. Lancet Oncol, 2018, 19(11): 1468-1479.
11. Park K, Özgüroğlu M, Vansteenkiste J, et al. Avelumab versus docetaxel in patients with platinum-treated advanced NSCLC: 2-year follow-up from the JAVELIN lung 200 phase 3 trial. J Thorac Oncol, 2021, 16(8): 1369-1378.
12. Sezer A, Kilickap S, Gümüş M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: A multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet, 2021, 397(10274): 592-604.
13. Zhou C, Chen G, Huang Y, et al. Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): A randomised, open-label, multicentre, phase 3 trial. Lancet Respir Med, 2021, 9(3): 305-314.
14. Reck M, Rodríguez-Abreu D, Robinson AG, 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): 2339-2349.
15. Carbone DP, Reck M, Paz-Ares L, et al. First-line nivolumab in stage Ⅳ or recurrent non-small-cell lung cancer. N Engl J Med, 2017, 376(25): 2415-2426.
16. de Castro G, Kudaba I, Wu YL, et al. Five-year outcomes with pembrolizumab versus chemotherapy as first-line therapy in patients with non-small-cell lung cancer and programmed death ligand-1 tumor proportion score≥1% in the KEYNOTE-042 study. J Clin Oncol, 2023, 41(11): 1986-1991.
17. Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med, 2020, 383(14): 1328-1339.
18. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med, 2018, 378(22): 2078-2092.
19. West H, McCleod M, Hussein M, 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): 924-937.
20. Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): An international, randomised, open-label, phase 3 trial. Lancet Oncol, 2021, 22(2): 198-211.
21. Gogishvili M, Melkadze T, Makharadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: A randomized, controlled, double-blind phase 3 trial. Nat Med, 2022, 28(11): 2374-2380.
22. Paz-Ares LG, Ramalingam SS, Ciuleanu TE, et al. First-line nivolumab plus ipilimumab in advanced nsclC: 4-year outcomes from the randomized, open-label, phase 3 CheckMate 227 part 1 trial. J Thorac Oncol, 2022, 17(2): 289-308.
23. Ren S, Chen J, Xu X, et al. Camrelizumab plus carboplatin and paclitaxel as first-line treatment for advanced squamous NSCLC (CameL-Sq): A phase 3 trial. J Thorac Oncol, 2022, 17(4): 544-557.
24. Zhou C, Wang Z, Sun Y, et al. Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): Interim and final analyses of a double-blind, randomised, phase 3 clinical trial. Lancet Oncol, 2022, 23(2): 220-233.
25. Cheng TY, Cramb SM, Baade PD, et al. The international epidemiology of lung cancer: Latest trends, disparities, and tumor characteristics. J Thorac Oncol, 2016, 11(10): 1653-1671.
26. Cetin K, Ettinger DS, Hei YJ, et al. Survival by histologic subtype in stageⅣ nonsmall cell lung cancer based on data from the Surveillance, Epidemiology and End Results Program. Clin Epidemiol, 2011, 3: 139-148.
27. Najafi M, Farhood B, Mortezaee K. Contribution of regulatory T cells to cancer: A review. J Cell Physiol, 2019, 234(6): 7983-7993.
28. Vinay DS, Ryan EP, Pawelec G, et al. Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Seminars in cancer biology. Academic Press, 2015, 35: S185-S198.
29. Abdel-Rahman O. Immune checkpoints aberrations and gastric cancer; assessment of prognostic value and evaluation of therapeutic potentials. Crit Rev Oncol Hematol, 2016, 97: 65-71.
30. Shimanovsky A, Dasanu CA. Updates on immunotherapy in non-small cell lung cancer. Expert Opin Biol Ther, 2014, 14(4): 411-418.
31. Sznol M, Chen L. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res, 2013, 19(5): 1021-1034.
32. 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(8): 793-800.
33. Kim DH, Kim H, Choi YJ, et al. Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer. Exp Mol Med, 2019, 51(8): 1-13.
34. Ribas A. Releasing the brakes on cancer immunotherapy. N Engl J Med, 2015, 373(16): 1490-1492.
35. Brito ABC, Camandaroba MPG, de Lima VCC. Anti-PD1 versus anti-PD-L1 immunotherapy in first-line therapy for advanced non-small cell lung cancer: A systematic review and meta-analysis. Thorac Cancer, 2021, 12(7): 1058-1066.
36. Zeng T, Qin Q, Bian Z, et al. Clinical efficacy and safety of anti-PD-1/PD-L1 treatments in non-small cell lung cancer (NSCLC). Artif Cells Nanomed Biotechnol, 2019, 47(1): 4194-4201.
37. Tran L, Allen CT, Xiao R, et al. Cisplatin alters antitumor immunity and synergizes with PD-1/PD-L1 inhibition in head and neck squamous cell carcinoma. Cancer Immunol Res, 2017, 5(12): 1141-1151.
38. Fournel L, Wu Z, Stadler N, et al. Cisplatin increases PD-L1 expression and optimizes immune check-point blockade in non-small cell lung cancer. Cancer Lett, 2019, 464: 5-14.
39. Ready N, Hellmann MD, Awad MM, et al. First-line nivolumab plus ipilimumab in advanced non-small-cell lung cancer (CheckMate 568): Outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers. J Clin Oncol, 2019, 37(12): 992-1000.
40. Jansen JP, Fleurence R, Devine B, et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: Report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: Part 1. Value Health, 2011, 14(4): 417-428.
41. Nishio M, Takahashi T, Yoshioka H, et al. KEYNOTE-025: Phase 1b study of pembrolizumab in Japanese patients with previously treated programmed death ligand 1-positive advanced non-small-cell lung cancer. Cancer Sci, 2019, 110(3): 1012-1020.
42. Leighl NB, Hellmann MD, Hui R, et al. Pembrolizumab in patients with advanced non-small-cell lung cancer (KEYNOTE-001): 3-year results from an open-label, phase 1 study. Lancet Respir Med, 2019, 7(4): 347-357.
43. Li ZQ, Yan HC, Gu JJ, et al. Comparative efficacy and safety of PD-1/PD-L1 Inhibitors versus platinum-based chemotherapy for the first-line treatment of advanced non-small cell lung cancer: A meta analysis of randomized controlled trials. Pharmacol Res, 2020, 160: 105194.
44. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial. Lancet, 2021, 398(10294): 27-40.
45. 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, 2015, 16(4): 375-384.
46. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med, 2015, 372(26): 2521-2532.
47. 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(2): 123-135.
48. Weber JS, Yang JC, Atkins MB, et al. Toxicities of immunotherapy for the practitioner. J Clin Oncol, 2015, 33(18): 2092-2099.
49. Ribas A, Kefford R, Marshall MA, et al. Phase Ⅲ randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol, 2013, 31(5): 616-622.
50. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med, 2010, 363(8): 711-723.
51. Alissafi T, Hatzioannou A, Legaki AI, et al. Balancing cancer immunotherapy and immune-related adverse events: The emerging role of regulatory T cells. J Autoimmun, 2019, 104: 102310.
52. Naidoo J, Page DB, Li BT, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol, 2015, 26(12): 2375-2391.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Latest ArticlesEfficacy and safety analysis of immune checkpoint inhibitors in the first-line treatment of patients with advanced NSCLC: A systematic evaluation and meta-analysis

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