Imunoterapie v léčbě karcinomu plic

Czech version

Authors: O. Fiala ^1,2; O. Šorejs ¹; M. Pešek ³; J. Fínek ¹
Authors‘ workplace: Onkologická a radioterapeutická klinika LF UK a FN Plzeň ¹; Biomedicínské centrum LF UK v Plzni ²; Klinika pneumologie a ftizeologie LF UK a FN Plzeň ³
Published in: Klin Onkol 2017; 30(Supplementum3): 22-31
Category: Review
doi: https://doi.org/10.14735/amko20173S22

Overview

Background:
Lung cancer occupies the leading position of cancer incidence and mortality worldwide, including in the Czech Republic. Despite significant advances in systemic oncology treatments, lung cancer still has the worst prognosis, which is driving the need for innovative therapies and methods to treat this disease. Immunotherapy is a developing area of systemic oncology treatment, which has recently begun to be significantly applied to patients with lung carcinoma. The most useful type of immunotherapy currently employs checkpoint inhibitors, including CTLA-4 inhibitors (ipilimumab and tremelimumab) and PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, durvalumab, and avelumab). Except for monotherapy, different combinations of these inhibitors or combinations between one more of these inhibitors and chemotherapy or targeted treatment are being actively studied. Despite intensive investigations, anti-tumor vaccines and cytokines have not had an important impact on the treatment of lung cancer. Checkpoint inhibitors have yielded favorable results, especially for the treatment of advanced (i.e., stage IIIB and IV) non-small cell lung cancer (NSCLC) and are being extensively investigated for the treatment of SCLC.

Aim:
The aim of this review was to summarize the most important achievements, possibilities, and perspectives of modern immunotherapy for the treatment of patients with lung cancer.

Conclusion:
Immunotherapy is an important tool in today’s arsenal of oncology treatments, and for patients with lung cancer it offers the hope of prolonging life and img iprovints quality.

Key words:
immunotherapy – lung cancer – NSCLC – SCLC – checkpoint inhibitors

This work was supported by National Sustainability Programme I No. LO1503 provided by Ministry of education, youth and sports and program No. 17-30748A devided by The Ministry of Health of the Czech Republic.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
31. 8. 2017

Accepted:
7. 9. 2017

Sources

1. Svod.cz. [online] Český národní webový portál epidemiologie nádorů. Masarykova univerzita, Česká republika. Dostupné na: http: //www.svod.cz.

2. Klener P, Klener P jr. Nová protinádorová léčiva a léčebné strategie v onkologii. 1. vyd. Praha: Grada Publishing 2010; 209.

3. Bartůňková J, Podrazil M, Špíšek R. Imunoterapie v léčbě nádorových onemocnění. Remedia 2015; 25 (1): 34–38.

4. Otáhal P, Trněný M. Současné možnosti imunoterapie nádorových onemocnění. Klin onkol 2015; 28 (Suppl 3): 105–111.

5. Domingues D, Turner A, Silva M et al. Immunotherapy and lung cancer: current developments and novel targeted therapies. Immunotherapy 2014; 6 (11): 1221–1235.

6. Bansal P, Osman D, Gan D et al. Recent Advances in Immunotherapy in Metastatic NSCLC. Front Oncol 2016; 6: 239. doi: 10.3389/fonc.2016.00239.

7. Mountzios G, Linardou H, Kosmidis P. Immunotherapy in non-small cell lung cancer: the clinical impact of immune response and targeting. Ann Transl Med 2016; 4 (14): 268. doi: 10.21037/atm.2016.06.24.

8. Wolchock J D, Hoos A., O’day S et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009; 15 (23): 7412–7420. doi: 10.1158/1078-0432.CCR-09-1624.

9. Klener P, Šťastný M. Posuzování léčebné odpovědi u zhoubných nádorů a potřeba úpravy kritérií pro hodnocení účinnosti imunoterapie. Remedia 2010; 20 (5): 332–336.

10. Lakomý R, Poprach A. Nežádoucí účinky moderní imunoterapie a jejich řešení v klinické praxi. Klin Onkol 2015; 28 (Suppl 4): 103–114.

11. Correale P, Tindara Miano S, Remondo C et al. Secondline treatment of non small cell lung cancer by biweekly gemcitabine and docetaxel +/-granulocyte-macrophage colony stimulating factor and low dose aldesleukine. Cancer Biol Ther 2009; 8 (6): 497–502. doi: 10.4161/cbt.8.6.7593.

12. Ridolfi L, Bertetto O, Santo A et al. Chemotherapy with or without low-dose interleukin-2 in advanced non-small cell lung cancer: results from a phase III randomized multicentric trial. Int J Oncol 2011; 39 (4): 1011–1017. doi: 10.3892/ijo.2011.1099.

13. Lissoni P, Brivio F, Fumagalli L et al. Neuroimmunomodulation in medical oncology: application of psychoneuroimmunology with subcutaneous low-dose IL-2 and the pineal hormone melatonin in patients with untreatable metastatic solid tumors. Anticancer Res 2008; 28 (2B): 1377–1381.

14. Pillai RN, Aisner J, Dahlberg SE et al. Interferon alpha plus 13-cis-retinoic acid modulation of BCL-2 plus paclitaxel for recurrent small-cell lung cancer (SCLC): An Eastern Cooperative Oncology Group study (E6501). Cancer Chemother Pharmacol 2014; 74 (1): 177–183. doi: 10.1007/s00280-014-2427-7.

15. Zarogoulidis K, Ziogas E, Boutsikou E et al. Immunomodifiers in combination with conventional chemotherapy in small cell lung cancer: Aphase II, randomized study. Drug Des Devel Ther 2013; 7: 611–617. doi: 10.2147/DDDT.S43184.

16. Schvartsman G, Ferrarotto R, Massarelli E. Checkpoint inhibitors in lung cancer: latest developments and clinical potential. Ther Adv Med Oncol 2016; 8 (6): 460–473. doi: 10.1177/1758834016661164.

17. Deel A. Nivolumab in metastatic non-small cell lung cancer. J Adv Pract Oncol 2016; 7 (2): 220–225.

18. Brahmer J, Reckamp K, L, 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. doi: 10.1056/NEJMoa1504627.

19. Borghaei H, Paz-Ares L, Horn L et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015; 373 (17): 1627–1639. doi: 10.1056/NEJMoa1507643.

20. 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. 10.1056/NEJMoa1613493.

21. Champiat S, Dercle L, Ammari 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): 1920–1928. doi: 10.1158/1078-0432.CCR-16-1741.

22. Antonia S J, López-Martin J A, Bendell J et al. Nivolumab alone and Nivolumab plus Ipilimumab in recurrent small-cell lung cancer (checkmate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol 2016; 17 (7): 883–895. doi: 10.1016/S1470-2045 (16) 30098-5.

23. A Safety Trial of Nivolumab in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed During or After Receiving At Least One Prior Chemotherapy Regimen (CheckMate153). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02066636.

24. Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC) (CheckMate 017). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT01642004.

25. Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Metastatic Non-squamous NSCLC (CheckMate057). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT01673867.

26. An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator’s Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer (CheckMate 026). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02041533.

27. An Investigational Immuno-therapy Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum-doublet Chemotherapy, Compared to Platinum Doublet Chemotherapy in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC) (CheckMate 227). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02477826.

28. An Investigational Immuno-therapy Study of Nivolumab, or Nivolumab in Combination With Ipilimumab, or Placebo in Patients With Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC) After Completion of Platinum-based Chemotherapy (CheckMate 451). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02538666.

29. Combination Checkpoint Inhibitor Plus Erlotinib or Crizotinib for EGFR or ALK Mutated Stage IV Non-small Cell Lung Cancer. Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT01998126.

30. Study of Safety and Efficacy of Ceritinib in Combination With Nivolumab in Patients With ALK-positive Non-small Cell Lung Cancer. Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02393625.

31. Ott PA, Elez E, Hiret S et al. Pembrolizumab for extensive stage SCLC: Efficacy and relationship with PD-L1 expression. Presented at: 16th World Conference on Lung Cancer. Denver, September 6–9 2015: abstract 3285.

32. Vachhani P, Chen H. Spotlight on Pembrolizumab in non-small cell lung cancer: the evidence to date. Onco Targets Ther 2016; 9: 5855–5866. doi: 10.2147/OTT.S97746.

33. Reck M, Rodríguez-Abreu D, Robinson A G et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016; 375 (19): 1823–1833. doi: 10.1056/NEJMoa1606774.

34. Study of MK-3475 (Pembrolizumab) Versus Platinum-based Chemotherapy for Participants With PD-L1-positive Advanced or Metastatic Non-small Cell Lung Cancer (MK-3475-042/KEYNOTE-042). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02220894.

35. Study of Pembrolizumab (MK-3475) vs Placebo for Participants With Non-small Cell Lung Cancer After Resection With or Without Standard Adjuvant Therapy (MK-3475-091/KEYNOTE-091) (PEARLS). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/ show/NCT02504372.

36. Pembrolizumab in Treating Patients With Extensive Stage Small Cell Lung Cancer After Completion of Combination Chemotherapy. Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02359019.

37. Wakelee H, Patel JD, Heist R et al. ORAL01.04: Phase II Trial of Atezolizumab for Patients with PD-L1-Selected Advanced NSCLC (BIRCH): Updated Efficacy and Exploratory Biomarker Results: Topic: Medical Oncology. J Thorac Oncol 2016; 11 (Suppl 11): 251–252. doi: 10.1016/j.jtho.2016.09.009.

38. Spigel DR, Chaft JE, Gettinger SC et al. Clinical activity and safety from a phase II study (FIR) of MPDL3280A (anti-PDL1) in PD-L1 selected patients with non-small-cell lung cancer (NSCLC). J Clin Oncol 2015; 33 (Suppl 15): 8028. doi: 0.1200/jco.2015.33.

39. 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. doi: 10.1016/S0140-6736 (16) 00587-0.

40. 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. doi: 10.1016/S0140-6736 (16) 32 517-X.

41. A Study of Atezolizumab (MPDL3280A) Compared With a Platinum Agent (Cisplatin or Carboplatin) + (Pemetrexed or Gemcitabine) in Participants With Stage IV Non-Squamous or Squamous Non-Small Cell Lung Cancer (NSCLC) [IMpower110]. Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02409342.

42. A Study of Atezolizumab in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Participants Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (IMpower 132). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02657434.

43. A Study of Atezolizumab (Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) in Combination With Carboplatin Plus (+) Nab-Paclitaxel Compared With Carboplatin + Nab-Paclitaxel in Participants With Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (IMpower130). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02367781.

44. A Study of Atezolizumab in Combination With Carboplatin + Paclitaxel or Carboplatin + Nab-Paclitaxel Compared With Carboplatin + Nab-Paclitaxel in Participants With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC) [IMpower131]. Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02367794.

45. A Study of Atezolizumab (Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) in Combination With Carboplatin Plus (+) Paclitaxel With or Without Bevacizumab Compared With Carboplatin+Paclitaxel+Bevacizumab in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (IMpower150). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02366143.

46. A Study of Atezolizumab Compared With Docetaxel in Non-Small Cell Lung Cancer (NSCLC) After Failure With Platinum-Containing Chemotherapy (IMpower210). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02813785.

47. Gulley J L, Rajan A, Spigel D R et al. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (javelin solid tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol 2017; 18 (5): 599–610. doi: 10.1016/S1470-2045 (17) 30240-1.

48. Avelumab in First-line Non-Small Cell Lung Cancer (JAVELIN Lung 100). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02576574.

49. Avelumab in Non-Small Cell Lung Cancer (JAVELIN Lung 200). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02395172.

50. Garassino MC, Vansteenkiste J F, Kim J et al. Durvalumab in ≥ 3rd-line locally advanced or metastatic, EGFR/alk wild-type NSCLC: results from the phase 2 atlantic study. J Thorac Oncol 2017; 12 (Suppl 1): 10–11. doi: 10.1016/j.jtho.2016.11.012.

51. Phase III Open Label First Line Therapy Study of MEDI 4736 (Durvalumab) With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC). (MYSTIC). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02453282.

52. Study of 1st Line Therapy Study of Durvalumab With Tremelimumab Versus SoC in Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE). (NEPTUNE). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02542293.

53. A Global Study to Assess the Effects of MEDI4736 Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02125461.

54. Phase II Study for Previously Untreated Subjects With Non Small Cell Lung Cancer (NSCLC) or Small Cell Lung Cancer (SCLC). Cinicaltrials.cz. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT00527735.

55. Lynch T J, Bondarenko I, Luft A et al. Ipilimumab in combination with Paclitaxel and Carboplatin as first-line treatment in stage IIIb/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol 2012; 30 (17): 2046–2054. doi: 10.1200/JCO.2011.38.4032.

56. Reck M, Bondarenko I, Luft A et al. Ipilimumab in combination with Paclitaxel and Carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol 2013; 24 (1): 75–83. doi: 10.1093/annonc/mds213.

57. Reck M, Luft A, Szczesna A et al. Phase III randomized trial of Ipilimumab plus Etoposide and Platinum versus placebo plus Etoposide and Platinum in extensive-stage small-cell lung cancer. J Clin Oncol 2016; pii: JCO676601. doi: 10.1200/JCO.2016.67.6601.

58. Cinicaltrials.cz. Phase 3 Trial in Squamous Non Small Cell Lung Cancer Subjects Comparing Ipilimumab Plus Paclitaxel and Carboplatin Versus Placebo Plus Paclitaxel and Carboplatin. [online] [last update posted: September 8, 2017]. Available from: https: //clinicaltrials.gov/ct2/show/NCT02279732.

59. Zatloukal P, Heo D S, Park K et al. Randomized phase II clinical trial comparing tremelimumab (CP-675,206) with best supportive care (BSC) following first-line platinum-based therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2009; 27 (Suppl 15): 8071–8071. doi: 10.1200/jco.2009.27.15s.8071.

60. Vansteekiste JF, Cho BC, Vanakesa T et al. Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2016; 17 (6): 822–835. doi: 10.1016/S1470-2045 (16) 000 99-1.

61. Butts C, Socinski MA, Mitchell P et al. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. Lancet Oncol 2014; 15 (1): 59–68. doi: 10.1016/S1470-2045 (13) 70510-2.

62. Giaccone G, Bazhenova LA, Nemunaitis J et al. A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer. Eur J Cancer 2015; 51 (16): 2321–2329. doi: 10.1016/j.ejca.2015.07.035.

63. Krug LM, Ragupathi G, Ng KK et al. Vaccination of small cell lung cancer patients with polysialic acid or N-propionylated polysialic acid conjugated to keyhole limpet hemocyanin. Clin Cancer Res 2004; 10 (3): 916–923.

64. Krug LM, Ragupathi G, Hood C et al. Immunization with N-propionyl polysialic acid-KLH conjugatein patients with small cell lung cancer is safeand induces IgM antibodies reactive with SCLC cells and bactericidal against group B meningococci. Cancer Immunol Immunother 2012; 61 (1): 9–18. doi: 10.1007/s00262-011-1083-6.

65. Giaccone G, Debruyne C, Felip E et al. Phase III study of adjuvant vaccination with Bec2/bacille Calmette-Guerin in responding patients with limited-disease small-cell lung cancer (European Organisation for Research and Treatment of Cancer 08971-08971B; Silva Study). J Clin Oncol 2005; 23 (28): 6854–6864. doi: 10.1200/ JCO.2005.17.186.

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Article was published in

Clinical Oncology

2017 Issue Supplementum3