Tyrosine kinase inhibitors in the treatment of advanced lung cancer from example of preferential medicine provision in Moscow city

Lung cancer is leading cause of death across oncological diseases. Nowadays, the therapy of lung cancer remains most serious problem of oncology. Targeted therapy including tyrosine kinase inhibitors (TKIs) is widely used in current clinical practice to treat advanced or metastatic non-small cell lung cancer. This paper reviews the clinical aspects of TKIs application in practical medicine. The article summarizes the results and outcomes of key clinical trials focused on efficiency and safety of TKIs, describes the results of analysis for TKIs need within the Moscow City Department of Healthcare system providing preferential medicines. The perspectives of future clinical developments of targeted treatments for lung cancer are postulated and discussed as well. Our previously unpublished data clearly demonstrate that gefitinib, erlotinib and afatinib turned out to be the most used TKIs for treatment of non-small cell lung cancer in the system of preferential medicine supply for Moscow population in 2018. The choice of targeted drugs directly depends on the molecular genetic profile of the tumor. To further improve the use of financial resources of the Moscow City Department of Healthcare it is essential to define accurately the molecular profile of the tumor specimens and prescribe the most effective TKIs for each individual case of lung cancer.

1. Amanam I., Gupta R., Mambetsariev I., Salgia R. The brigatinib experience: a new generation of therapy for ALKpositive non-small-cell lung cancer. Future Oncol. 2018; 14 (19): 1897–1908. DOI: 10.2217/fon-2017-0545.

2. Kaprin A.D., Starin - skiy V.V., Petrova G.V., red. [Malignant neoplasms in Russia in 2016 (incidence and mortality)]. Moscow: MNIOI im. P.A.Gertsena – filial FGBU «NMITs radiologii» Min - zdrava Rossii; 2018. Available at: https://oncology-association.ru/files/medstat/2016.pdf (in Russian).

3. Zugazagoitia J., Molina-Pinelo S., Lopez-Rios F., PazAres L. Biological therapies in nonsmall cell lung cancer. Eur. Respir. J. 2017; 49 (3): 1601520. DOI: 10.1183/13993003.01520-2016.

4. Wang Y., Hu G.F., Wang Z.H. The status of immunosuppression in patients with stage IIIB or IV non-small-cell lung cancer correlates with the clinical characteristics and response to chemotherapy. Onco Targets Ther. 2017; 10: 3557–3566. DOI: 10.2147/OTT.S136259.

5. Gadgeel S.M. Personalized therapy of non-small cell lung cancer (NSCLC). Adv. Exp. Med. Biol. 2016; 890: 203–222. DOI: 10.1007/978-3-319-24932-2_11.

6. Chan B.A., Hughes B.G.M. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl. Lung Cancer Res. 2015; 4 (1): 36–54. DOI: 10.3978/j.issn.2218-6751.2014.05.01.

7. Alamgeer M., Ganju V., Watkins D.N. Novel therapeutic targets in non-small cell lung cancer. Curr. Opin. Pharmacol. 2013; 13 (3): 394–401. DOI: 10.1016/j.coph.2013.03.010.

8. Savas P., Hughes B., Solomon B. Targeted therapy in lung cancer: IPASS and beyond, keeping abreast of the explosion of targeted therapies for lung cancer. J. Thorac. Dis. 2013; 5 (Suppl. 5): S579–592. DOI: 10.3978/j.issn.2072-1439.2013.08.52.

9. Keedy V.L., Temin S., Somerfield M.R. et al. American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J. Clin. Oncol. 2011; 29 (15): 2121–2127. DOI: 10.1200/JCO.2010.31.8923.

10. Califano R., Greystoke A., Lal R. et al. Management of ceritinib therapy and adverse events in patients with ALKrearranged non-small cell lung cancer. Lung Cancer. 2017; 111: 51–58. DOI: 10.1016/j.lungcan.2017.06.004.

11. Weart T.C., Miller K.D., Simone C.B. Spotlight on dabra - fenib/trametinib in the treatment of non-small-cell lung cancer: place in therapy. Cancer Manag. Res. 2018; 10: 647– 652. DOI: 10.2147/CMAR.S142269.

12. Nivolumab approved for lung cancer. Cancer Discov. 2015; 5 (5): OF 1. DOI: 10.1158/2159-8290.CD-NB2015-042.

13. Ranson M., Hammond L.A., Ferry D. et al. ZD1839, a selec tive oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial. J. Clin. Oncol. 2002; 20 (9): 2240–2250. DOI: 10.1200/JCO.2002.10.112.

14. Ho C., Murray N., Laskin J. et al. Asian ethnicity and adenocarcinoma histology continues to predict response to gefitinib in patients treated for advanced non-small cell carcinoma of the lung in North America. Lung Cancer. 2005; 49 (2): 225–231. DOI: 10.1016/j.lungcan.2005.02.011.

15. Giaccone G., Herbst R.S., Manegold C. et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial–INTACT 1. J. Clin. Oncol. 2004; 22 (5): 777–784. DOI: 10.1200/JCO.2004.08.001.

16. Herbst R.S., Giaccone G., Schiller J.H. et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial–INTACT 2. J. Clin. Oncol. 2004; 22 (5): 785–794. DOI: 10.1200/JCO.2004.07.215.

17. Kim E.S., Hirsh V., Mok T. et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008; 372 (9652): 1809–1818. DOI: 10.1016/S0140-6736(08)61758-4.

18. Maruyama R., Nishiwaki Y., Tamura T. et al. Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell lung cancer. J. Clin. Oncol. 2008; 26 (26): 4244–4252. DOI: 10.1200/JCO.2007.15.0185.

19. Lee D.H., Park K., Kim J.H. et al. Randomized phase III trial of gefitinib versus docetaxel in non-small cell lung cancer patients who have previously received platinum-based chemotherapy. Clin. Cancer Res. 2010; 16 (4): 1307–1314. DOI: 10.1158/1078-0432.CCR-09-1903.

20. Thatcher N., Chang A., Parikh P. et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005; 366 (9496): 1527–1537. DOI: 10.1016/S0140-6736(05)67625-8.

21. Shepherd F.A., Rodrigues Pereira J., Ciuleanu T. et al. Erlotinib in previously treated non-small-cell lung cancer. N. Engl. J. Med. 2005; 353 (2): 123–132. DOI: 10.1056/NEJMoa050753.

22. Shea M., Costa D.B., Rangachari D. Management of advanced non-small cell lung cancers with known mutations or rearrangements: latest evidence and treatment approaches. Ther. Adv. Respir. Dis. 2016; 10 (2): 113–129. DOI: 10.1177/1753465815617871.

23. Sequist L.V., Yang J.C.H., Yamamoto N. et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J. Clin. Oncol. 2013; 31 (27): 3327–3334. DOI: 10.1200/JCO.2012.44.2806.

24. Mok T.S., Wu Y.L., Thongprasert S. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med. 2009; 361 (10): 947–957. DOI: 10.1056/NEJMoa0810699.

25. Mitsudomi T., Morita S., Yatabe Y. et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010; 11 (2): 121–128. DOI: 10.1016/S1470-2045(09)70364-X.

26. Maemondo M., Inoue A., Kobayashi K. et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N. Engl. J. Med. 2010; 362 (25): 2380–2388. DOI: 10.1056/NEJMoa0909530.

27. Zhou C., Wu Y.L., Chen G. et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011; 12 (8): 735–742. DOI: 10.1016/S1470-2045(11)70184-X.

28. Rosell R., Carcereny E., Gervais R. et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-smallcell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012; 13 (3): 239–246. DOI: 10.1016/S1470-2045(11)70393-X.

29. Yeo W.L., Riely G.J., Yeap B.Y. et al. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J. Thorac. Oncol. 2010; 5 (7): 1048–1053. DOI: 10.1097/JTO.0b013e3181dd1386.

30. Janne P.A., Yang J.C.H., Kim D.W. et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N. Engl. J. Med. 2015; 372 (18): 1689–1699. DOI: 10.1056/NEJMoa1411817.

31. Sequist L.V., Soria J.C., Goldman J.W. et al. Rociletinib in EGFR-mutated non-small-cell lung cancer. N. Engl. J. Med. 2015; 372 (18): 1700–1709. DOI: 10.1056/NEJMoa1413654.

32. Ramalingam S.S., Yang J.C.H., Lee C.K. et al. Osimertinib as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer. J. Clin. Oncol. 2018; 36 (9): 841–849. DOI: 10.1200/JCO.2017.74.7576.

33. Kwak E.L., Bang Y.J., Camidge D.R. et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N. Engl. J. Med. 2010; 363 (18): 1693–1703. DOI: 10.1056/NEJMoa1006448.

34. Camidge D.R., Bang Y.J., Kwak E.L. et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012; 13 (10): 1011–1019. DOI: 10.1016/S1470-2045(12)70344-3.

35. Shaw A.T., Kim D.W., Nakagawa K. et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N. Engl. J. Med. 2013; 368 (25): 2385–2394. DOI: 10.1056/NEJMoa1214886.

36. Solomon B.J., Mok T., Kim D.W. et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N. Engl. J. Med. 2014; 371 (23): 2167–2177. DOI: 10.1056/NEJMoa1408440.

37. Shaw A.T., Kim D.W., Mehra R. et al. Ceritinib in ALKrearranged non-small-cell lung cancer. N. Engl. J. Med. 2014; 370 (13): 1189–1197. DOI: 10.1056/NEJMoa1311107.

38. Soria J.C., Tan D.S.W., Chiari R. et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALKrearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017; 389 (10072): 917–929. DOI: 10.1016/S0140-6736(17)30123-X.

39. Hirsch F.R., Suda K., Wiens J. et al. New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 2016; 388 (10048): 1012–1024. DOI: 10.1016/S0140-6736(16)31473-8.

40. Peters S., Camidge D.R., Shaw A.T. et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N. Engl. J. Med. 2017; 377 (9): 829–838. DOI: 10.1056/NEJMoa1704795.

41. Gettinger S.N., Bazhenova L.A., Langer C.J. et al. Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, openlabel, phase 1/2 trial. Lancet Oncol. 2016; 17 (12): 1683– 1696. DOI: 10.1016/S1470-2045(16)30392-8.

42. Planchard D., Kim T.M., Mazieres J. et al. Dabrafenib in patients with BRAF(V600E)-positive advanced non-smallcell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016; 17 (5): 642–650. DOI: 10.1016/S1470-2045(16)00077-2.

43. Planchard D., Besse B., Groen H.J.M. et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016; 17 (7): 984–993. DOI: 10.1016/S1470-2045(16)30146-2.

44. Planchard D., Smit E.F., Groen H.J.M. et al. Dabrafenib plus trametinib in patients with previously untreated BRAF(V600E)-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017; 18 (10): 1307–1016. DOI: 10.1016/S1470-2045(17)30679-4.

45. Lehman J.M., Gwin M.E., Massion P.P. Immunotherapy and targeted therapy for small cell lung cancer: there is hope. Curr. Oncol. Rep. 2017; 19 (7): 49. DOI: 10.1007/s11912-017-0609-2.

46. Schoffski P., Besse B., Gauler T. et al. Efficacy and safety of biweekly i.v. administrations of the Aurora kinase inhibitor danusertib hydrochloride in independent cohorts of patients with advanced or metastatic breast, ovarian, colorectal, pancreatic, small-cell and non-small-cell lung cancer: a multitumour, multi-institutional phase II study. Ann Oncol. 2015; 26 (3): 598–607. DOI: 10.1093/annonc/mdu566.

47. Melichar B., Adenis A., Lockhart A.C. et al. Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamouscell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study. Lancet Oncol. 2015; 16 (4): 395–405. DOI: 10.1016/S1470-2045(15)70051-3.