Research progress in atezolizumab in the treatment of lung cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

FANG Tao ^1,2 , LEI Xiang ¹ ,  SONG Bing ³

1. The First Clinical Medical College of The First Hospital of Lanzhou University, Lanzhou, 730000, P.R.China;
2. Department of Emergency, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, P.R.China;
3. The First Hospital of Lanzhou University, Lanzhou, 730000, P.R.China;

Corresponding author：

SONG Bing, Email: hnfangss@163.com

Keywords：

Atezolizumab; programmed death-ligand 1; lung cancer; review

DOI：

10.7507/1007-4848.202008037

Video：

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In recent years, atezolizumab, a programmed death-ligand 1 (PD-L1) has shown clinical efficacies against many different solid malignancies. In late October 2016, the Food and Drug Administration (FDA) granted approval to atezolizumab for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy. With the development of clinical trials, the applications of atezolizumab in lung cancer treatment have gradually expanded. In this review, we summarized the current clinical status of atezolizumab in the treatment of lung cancer.

Citation： FANG Tao, LEI Xiang, SONG Bing. Research progress in atezolizumab in the treatment of lung cancer. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2022, 29(1): 114-120. doi: 10.7507/1007-4848.202008037 Copy

1.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
2.	Bade BC, Dela Cruz CS. Lung cancer 2020: Epidemiology, etiology, and prevention. Clin Chest Med, 2020, 41(1): 1-24.
3.	Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer staging project: Proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol, 2016, 11(1): 39-51.
4.	Tsoukalas N, Aravantinou-Fatorou E, Baxevanos P, et al. Advanced small cell lung cancer (SCLC): New challenges and new expectations. Ann Transl Med, 2018, 6(8): 145.
5.	Sun C, Mezzadra R, Schumacher TN. Regulation and function of the PD-L1 checkpoint. Immunity, 2018, 48(3): 434-452.
6.	Sun Z, Fourcade J, Pagliano O, et al. IL10 and PD-1 cooperate to limit the activity of tumor-specific CD8⁺ T cells. Cancer Res, 2015, 75(8): 1635-1644.
7.	Paterson AM, Brown KE, Keir ME, et al. The programmed death-1 ligand 1: B7-1 pathway restrains diabetogenic effector T cells in vivo. J Immunol, 2011, 187(3): 1097-1105.
8.	Akinleye A, Rasool Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J Hematol Oncol, 2019, 12(1): 92.
9.	Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature, 2014, 515(7528): 563-567.
10.	Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature, 2014, 515(7528): 558-562.
11.	Inman BA, Longo TA, Ramalingam S, et al. Atezolizumab: A PD-L1-blocking antibody for bladder cancer. Clin Cancer Res, 2017, 23(8): 1886-1890.
12.	Deng R, Bumbaca D, Pastuskovas CV, et al. Preclinical pharmacokinetics, pharmacodynamics, tissue distribution, and tumor penetration of anti-PD-L1 monoclonal antibody, an immune checkpoint inhibitor. MAbs, 2016, 8(3): 593-603.
13.	Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med, 2018, 379(22): 2108-2121.
14.	Rini BI, Powles T, Atkins MB, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): A multicentre, open-label, phase 3, randomised controlled trial. Lancet, 2019, 393(10189): 2404-2415.
15.	Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: A single-arm, multicentre, phase 2 trial. Lancet, 2017, 389(10064): 67-76.
16.	Ettinger DS, Wood DE, Aisner DL, et al. Non-small cell lung cancer, version 5.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2017, 15(4): 504-535.
17.	Leora Horn, Spigel David R, Gettinger Scott N, et al. Clinical activity, safety and predictive biomarkers of the engineered antibody MPDL3280A (anti-PDL1) in non-small cell lung cancer (NSCLC): Update from a phaseⅠA study. J Clin Oncol, 2015, 33(15_suppl): 8029.
18.	Fehrenbacher L, Spira A, Ballinger M, et al. 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, 387(10030): 1837-1846.
19.	Rittmeyer A, Barlesi F, Waterkamp D, et al. 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): 255-265.
20.	Peters S, Gettinger S, Johnson ML, et al. PhaseⅡ 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): 2781-2789.
21.	Spigel DR, Chaft JE, Gettinger S, et al. FIR: Efficacy, safety, and biomarker analysis of a phase Ⅱ open-label study of atezolizumab in PD-L1-selected patients with NSCLC. J Thorac Oncol, 2018, 13(11): 1733-1742.
22.	Spigel D, De Marinis F, Giaccone G, et al. LBA78 - IMpower110: Interim overall survival (OS) analysis of a phaseⅢ study of atezolizumab (atezo)vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1-selected NSCLC. Ann Oncol, 2019, 30(Suppl 5): v915.
23.	Liu SV, Camidge DR, Gettinger SN, et al. Atezolizumab (atezo) plus platinum-based chemotherapy (chemo) in non-small cell lung cancer (NSCLC): Update from a phase ⅠB study. J Clin Oncol, 2017, 35(15_suppl): 9092.
24.	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.
25.	Papadimitrakopoulou V, Cobo M, Bordoni R, et al. OA05.07 IMpower132: PFS and safety results with 1L atezolizumab+carboplatin/cisplatin+pemetrexed in stage Ⅳ non-squamous NSCLC. J Thorac Oncol, 2018, 13(10): S332-S333.
26.	Jotte R, Cappuzzo F, Vynnychenko I, et al. Atezolizumab in combination with carboplatin and nab-paclitaxel in advanced squamous NSCLC (IMpower131): Results from a randomized phase Ⅲ trial. J Thorac Oncol, 2020, 15(8): 1351-1360.
27.	Socinski MA, Mok TSK, Nishio M. IMpower150 final analysis: Efficacy of atezolizumab (atezo)+ bevacizumab (bev) and chemotherapy in first-line (1L) metastatic nonsquamous (nsq) non-small cell lung cancer (NSCLC) across key subgroups. 2020 AACR: abstract CT216.
28.	Reck M, Liu SV, Mansfield AS, et al. 1736O - IMpower133: Updated overall survival (OS) analysis of first-line (1L) atezolizumab (atezo)+carboplatin+etoposide in extensive-stage SCLC (ES-SCLC). Ann Oncol, 2019, 30: v710-v711.
29.	Aguiar PN Jr, De Mello RA, Barreto CMN, et al. Immune checkpoint inhibitors for advanced non-small cell lung cancer: Emerging sequencing for new treatment targets. ESMO Open, 2017, 2(3): e000200.
30.	Willett CG, Boucher Y, di Tomaso E, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med, 2004, 10(2): 145-147.
31.	Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med, 2018, 378(24): 2288-2301.
32.	Shu CA, Gainor JF, Awad MM, et al. Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: An open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol, 2020, 21(6): 786-795.
33.	Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage Ⅲ NSCLC. N Engl J Med, 2018, 379(24): 2342-2350.
34.	Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): A randomized, controlled, open-label, phase 3 trial. Lancet, 2019, 394(10212): 1929-1939.
35.	Powles T, O'donnell PH, Massard C, et al. Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: Updated results from a phase 1/2 open-label study. JAMA Oncol, 2017, 3(9): e172411.
36.	Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med, 2019, 380(12): 1103-1115.
37.	Patel MR, Ellerton J, Infante JR, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN solid tumor): Pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol, 2018, 19(1): 51-64.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
2. Bade BC, Dela Cruz CS. Lung cancer 2020: Epidemiology, etiology, and prevention. Clin Chest Med, 2020, 41(1): 1-24.
3. Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer staging project: Proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol, 2016, 11(1): 39-51.
4. Tsoukalas N, Aravantinou-Fatorou E, Baxevanos P, et al. Advanced small cell lung cancer (SCLC): New challenges and new expectations. Ann Transl Med, 2018, 6(8): 145.
5. Sun C, Mezzadra R, Schumacher TN. Regulation and function of the PD-L1 checkpoint. Immunity, 2018, 48(3): 434-452.
6. Sun Z, Fourcade J, Pagliano O, et al. IL10 and PD-1 cooperate to limit the activity of tumor-specific CD8⁺ T cells. Cancer Res, 2015, 75(8): 1635-1644.
7. Paterson AM, Brown KE, Keir ME, et al. The programmed death-1 ligand 1: B7-1 pathway restrains diabetogenic effector T cells in vivo. J Immunol, 2011, 187(3): 1097-1105.
8. Akinleye A, Rasool Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J Hematol Oncol, 2019, 12(1): 92.
9. Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature, 2014, 515(7528): 563-567.
10. Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature, 2014, 515(7528): 558-562.
11. Inman BA, Longo TA, Ramalingam S, et al. Atezolizumab: A PD-L1-blocking antibody for bladder cancer. Clin Cancer Res, 2017, 23(8): 1886-1890.
12. Deng R, Bumbaca D, Pastuskovas CV, et al. Preclinical pharmacokinetics, pharmacodynamics, tissue distribution, and tumor penetration of anti-PD-L1 monoclonal antibody, an immune checkpoint inhibitor. MAbs, 2016, 8(3): 593-603.
13. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med, 2018, 379(22): 2108-2121.
14. Rini BI, Powles T, Atkins MB, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): A multicentre, open-label, phase 3, randomised controlled trial. Lancet, 2019, 393(10189): 2404-2415.
15. Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: A single-arm, multicentre, phase 2 trial. Lancet, 2017, 389(10064): 67-76.
16. Ettinger DS, Wood DE, Aisner DL, et al. Non-small cell lung cancer, version 5.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2017, 15(4): 504-535.
17. Leora Horn, Spigel David R, Gettinger Scott N, et al. Clinical activity, safety and predictive biomarkers of the engineered antibody MPDL3280A (anti-PDL1) in non-small cell lung cancer (NSCLC): Update from a phaseⅠA study. J Clin Oncol, 2015, 33(15_suppl): 8029.
18. Fehrenbacher L, Spira A, Ballinger M, et al. 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, 387(10030): 1837-1846.
19. Rittmeyer A, Barlesi F, Waterkamp D, et al. 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): 255-265.
20. Peters S, Gettinger S, Johnson ML, et al. PhaseⅡ 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): 2781-2789.
21. Spigel DR, Chaft JE, Gettinger S, et al. FIR: Efficacy, safety, and biomarker analysis of a phase Ⅱ open-label study of atezolizumab in PD-L1-selected patients with NSCLC. J Thorac Oncol, 2018, 13(11): 1733-1742.
22. Spigel D, De Marinis F, Giaccone G, et al. LBA78 - IMpower110: Interim overall survival (OS) analysis of a phaseⅢ study of atezolizumab (atezo)vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1-selected NSCLC. Ann Oncol, 2019, 30(Suppl 5): v915.
23. Liu SV, Camidge DR, Gettinger SN, et al. Atezolizumab (atezo) plus platinum-based chemotherapy (chemo) in non-small cell lung cancer (NSCLC): Update from a phase ⅠB study. J Clin Oncol, 2017, 35(15_suppl): 9092.
24. 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.
25. Papadimitrakopoulou V, Cobo M, Bordoni R, et al. OA05.07 IMpower132: PFS and safety results with 1L atezolizumab+carboplatin/cisplatin+pemetrexed in stage Ⅳ non-squamous NSCLC. J Thorac Oncol, 2018, 13(10): S332-S333.
26. Jotte R, Cappuzzo F, Vynnychenko I, et al. Atezolizumab in combination with carboplatin and nab-paclitaxel in advanced squamous NSCLC (IMpower131): Results from a randomized phase Ⅲ trial. J Thorac Oncol, 2020, 15(8): 1351-1360.
27. Socinski MA, Mok TSK, Nishio M. IMpower150 final analysis: Efficacy of atezolizumab (atezo)+ bevacizumab (bev) and chemotherapy in first-line (1L) metastatic nonsquamous (nsq) non-small cell lung cancer (NSCLC) across key subgroups. 2020 AACR: abstract CT216.
28. Reck M, Liu SV, Mansfield AS, et al. 1736O - IMpower133: Updated overall survival (OS) analysis of first-line (1L) atezolizumab (atezo)+carboplatin+etoposide in extensive-stage SCLC (ES-SCLC). Ann Oncol, 2019, 30: v710-v711.
29. Aguiar PN Jr, De Mello RA, Barreto CMN, et al. Immune checkpoint inhibitors for advanced non-small cell lung cancer: Emerging sequencing for new treatment targets. ESMO Open, 2017, 2(3): e000200.
30. Willett CG, Boucher Y, di Tomaso E, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med, 2004, 10(2): 145-147.
31. Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med, 2018, 378(24): 2288-2301.
32. Shu CA, Gainor JF, Awad MM, et al. Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: An open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol, 2020, 21(6): 786-795.
33. Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage Ⅲ NSCLC. N Engl J Med, 2018, 379(24): 2342-2350.
34. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): A randomized, controlled, open-label, phase 3 trial. Lancet, 2019, 394(10212): 1929-1939.
35. Powles T, O'donnell PH, Massard C, et al. Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: Updated results from a phase 1/2 open-label study. JAMA Oncol, 2017, 3(9): e172411.
36. Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med, 2019, 380(12): 1103-1115.
37. Patel MR, Ellerton J, Infante JR, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN solid tumor): Pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol, 2018, 19(1): 51-64.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Research progress in atezolizumab in the treatment of lung cancer

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