COST-EFFECTIVENESS ANALYSIS OF BRENTUXIMAB VEDOTIN IN ADULTS WITH RELAPSED OR REFRACTORY HODGKIN’S LYMPHOMA

Objective: to perform cost-effectiveness analysis of brentuximab vedotin (BV) in patients with relapsed or refractory CD30-positive Hodgkin’s lymphoma (HL).

Materials and methods. This study was performed in two parts in 2015. In the first part Markov model was built on the basis of the results of cohort prospective and retrospective studies and clinical expert survey to assess cost-effectiveness of BV in patients with relapsed or refractory CD30-positive HL. Time horizon of the model was 40 years. The model simulated transition between three health states: progression-free, post-progression and death for patients with relapsed or refractory CD30-positive HL after autologous stem cell transplantation (ASCT). Three alternatives were analyzed: 1) chemotherapy with or without radiotherapy (Ch ± RT), 2) Ch ± RT with allogeneic stem cell transplantation (alloSCT) and 3) BV. The economic evaluation was made from the Russian healthcare system point of view. Incremental cost-effectiveness ratio (ICER) for BV vs Ch ± RT and Ch ± RT + alloSCT vs Ch ± RT per life year (LY) and quality-adjusted life year (QALY) was calculated. In the second part we calculated ICER for BV vs standard treatment based on drugs costs only and compared it with ICER for some other costly oncologic drugs, calculated by the same approach. Drugs used for ICER comparison were: bevacizumab for metastatic renal cell carcinoma, eribulin for metastatic breast cancer, panitumumab for adenocarcinoma of the colon or rectum and cabazitaxel for metastatic castration-resistant prostate cancer. ICER was calculated separately for each single drug as the ratio of increment costs of analyzed drug vs the comparator and the increment overall survival; data was derived from clinical trials.

Results. In patients with relapsed or refractory CD30-positive HL after ASCT ICER was 5,8 million rub. per LY for BV vs Ch ± RT and 6,4 million rub. for Ch ± RT + alloSCT vs Ch ± RT. Cost of additional month of life for BV in patients with relapsed or refractory CD30-positive HL after ASCT was 524 thousand rub. that was lower than for bevacizumab for metastatic renal cell carcinoma and eribulin for metastatic breast cancer, both drugs included into 2016 Essential and Vital Drugs List: 2,5 million rub. and 923 thousand rub., respectively.

Conclusion. In patients with relapsed or refractory CD30- positive HL after ASCT BV is an appropriate alternative as ICER per LY is lower than for standard treatment Ch ± RT + alloSCT vs Ch ± RT. Cost of additional month of life is lower than for other oncologic drugs included into Russian Essential and Vital Drugs List.

1. Zelenova O.V. Menedzher zdravookhraneniya. 2011; 6. Rezhim dostupa: http://cyberleninka.ru/article/n/sovremennye-metody-issledovaniya-poroga-gotovnosti-platit-v-sfere-zdravoohraneniya. Data obrashcheniya: 16.10.2015.

2. Malignancies in Russia in 2013 (morbidity and mortality). Ed. A.D. Caprin, VV Starinskiy, G.V. Petrova. Moscow Research Institute of Oncology named after PA Herzen Ministry of Health of Russia [Zlokachestvennye novoobrazovaniya v Rossii v 2013 godu (zabolevaemost' i smertnost'). Pod red. A.D. Kaprina, V.V. Starinskogo, G.V. Petrovoi. MNIOI im. P.A. Gertsena – filial FGBU «FMITs im. P.A. Gertsena» Minzdrava Rossii (in Russian)]. 2015; 250 s.

3. Basic derived indicators of the dynamics of the exchange rate of the ruble in January-November 2015, the Central Bank of the Russian Federation [Osnovnye proizvodnye pokazateli dinamiki obmennogo kursa rublya v yanvare-noyabre 2015 goda, TsB RF (in Russian)]. URL: http://www.cbr.ru/statistics/print.aspx?file=credit_statistics/ex_rate_ind_15. htm&pid=svs&sid=analit. Accessed: 16.10.2015.

4. On the production and use of gross domestic product (GDP) for 2014, Rosstat 2015 [O proizvodstve i ispol'zovanii valovogo vnutrennego produkta (VVP) za 2014 g., Rosstat 2015 g. (in Russian)]. URL: http://www.gks.ru/bgd/free/b04_03/Isswww.exe/Stg/d05/18vvp2.htm. Accessed: 16.10.2015.

5. Russian Federation Government Resolution dated November 28, 2014 N 1273 "About state guarantees of rendering free medical care to citizens for 2015 and the planning period of 2016 and 2017" [Postanovlenie Pravitel'stva Rossiiskoi Federatsii ot 28 noyabrya 2014 g. N 1273 «O programme gosudarstvennykh garantii besplatnogo okazaniya grazhdanam meditsinskoi pomoshchi na 2015 god i na planovyi period 2016 i 2017 godov» (in Russian)].

6. Decree of the Russian Government dated 26 December 2015 № 2724-r "On approval of the list of vital and essential drugs for 2016, as well as lists of drugs for medical use and minimal assortment of drugs needed for medical care." [Rasporyazhenie Pravitel'stva RF ot 26 dekabrya 2015 g. № 2724-r «Ob utverzhdenii perechnya zhiznenno neobkhodimykh i vazhneishikh lekarstvennykh preparatov na 2016 god, a takzhe perechnei lekarstvennykh preparatov dlya meditsinskogo primeneniya i minimal'nogo assortimenta lekarstvennykh preparatov, neobkhodimykh dlya okazaniya meditsinskoi pomoshchi» (in Russian)]. URL: http://www.consultant.ru/document/cons_doc_LAW_192036/. Accessed: 16.10.2015.

7. Russian clinical guidelines for the diagnosis and treatment of lymphoproliferative disorders. Under the guidance of prof. IV Poddubnaya, prof. VG Savchenko [Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniyu limfoproliferativnykh zabolevanii. Pod rukovodstvom prof. I.V. Poddubnoi, prof. V.G. Savchenko (in Russian)]. Moscow. 2014; 128 s.

8. Tariff agreement for the payment of medical assistance for the territorial program of compulsory health insurance the city of Moscow for 2015 on December 25, 2014 [Tarifnoe soglashenie na oplatu meditsinskoi pomoshchi, okazyvaemoi po territorial'noi programme obyazatel'nogo meditsinskogo strakhovaniya goroda Moskvy na 2015 god ot 25 dekabrya 2014 g. (in Russian)]. URL: http://www.mgfoms.ru/system/files/tarifnoe_soglashenie_territorialnoy_oms_2015_god.pdf. Accessed: 16.10.2015.

9. Fees for medical services Moscow city registry of medical services in the CHI system tariffs for medical services, entered into force on 01.10.2014. [Tarify na meditsinskie uslugi Moskovskogo gorodskogo reestra meditsinskikh uslug v sisteme OMS Tarify na meditsinskie uslugi, vvedennye v deistvie s 01.10.2014 (in Russian)]. URL: http://www.mgfoms.ru/system/files/fokt1014.xls. Accessed: 16.10.2015.

10. The number of Russian population by municipalities in 2014 Rosstat 2015 [Chislennost' naseleniya Rossiiskoi Federatsii po munitsipal'nym obrazovaniyam v 2014 g. Rosstat 2015 g. (in Russian)]. URL: http://www.gks.ru/wps/wcm/connect/rosstat_main/rosstat/ru/statistics/publications/catalog/afc8ea004d56a39ab251f2bafc3a6fce. Accessed: 16.10.2015.

11. Arai S., Fanale M., DeVos S. et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013 Nov; 54 (11): 2531-3. DOI: 10.3109/10428194.2013.798868. Epub 2013 Jun 5.

12. De Bono J.S., Oudard S., Ozguroglu M et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2; 376 (9747): 1147-54. DOI: 10.1016/S0140-6736(10)61389-X.

13. Diehl V., Sieber M., Ruffer U. et al. BEACOPP: an intensified chemotherapy regimen in advanced Hodgkin disease. The German Hodgkin Lymphoma Study Group. Ann Oncol. 1997; (2): 143-8.

14. Eichenauer D.A., Engert A., André M. et al. Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014 Sep; 25 Suppl 3: iii70-5. DOI: 10.1093/annonc/mdu181.Epub 2014 Jul 25.

15. El Gnaoui T., Dupuis J., Belhadj K. et al. Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol. 2007; (8): 1363-8.

16. Gopal A.K., Chen R., Smith S.E. et al. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2015 Feb 19; 125 (8): 1236-43. DOI: 10.1182/blood-2014-08-595801. Epub 2014 Dec 22.

17. Gopal A., Chen R., Smith S. et al. Three-Year Follow-Up Data and Characterization Of Long-Term Remissions From An Ongoing Phase 2 Study Of Brentuximab Vedotin In Patients With Relapsed Or Refractory Hodgkin Lymphoma. American Society of Hematology Meeting 2013, abstract №4382. URL: https://ash.confex.com/ash/2013/webprogram/Paper57589.html. Accessed: 16.10.2015.

18. Heider A., Niederle N. Efficacy and toxicity of bendamustine in patients with relapsed low-grade non-Hodgkin lymphomas. Anticancer Drugs. 2001; 9: 725-9.

19. Hoppe R.T., Advani R.H., Ai W.Z. et al. Hodgkin lymphoma, version 2.2015. J Natl Compr Canc Netw. 2015 May; 13 (5): 554-86.

20. Josting A., Rudolph C., Reiser M. et al. Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin disease. Ann Oncol. 2002; 10: 1628-35.

21. Kaufman P.A., Awada A., Twelves C. et al. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015 Feb 20; 33 (6): 594-601. DOI: 10.1200/JCO.2013.52.4892. Epub 2015 Jan 20.

22. Martinez C., Canals C., Alessandrino E.P. et al. Relapse of Hodgkin’s lymphoma after autologous stem cell transplantation (ASCT): identification of prognostic factors predicting outcome. Presentation at the 8th International Symposium on Hodgkin Lymphoma (ISHL), Cologne, October 26th.

23. Martinez C., Canals C., Sarina B. et al. Identification of prognostic factors predicting outcome in Hodgkin's lymphoma patients relapsing after autologous stem cell transplantation. Ann Oncol. 2013 Sep; 24 (9): 2430-4. DOI: 10.1093/annonc/mdt206. Epub 2013 May 26.

24. Ng M., Waters J., Cunningham D. et al. Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma. Br J Cancer. 2005 (8): 1352-7.

25. Price T.J., Peeters M., Kim T.W. et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014 May; 15 (6): 569-79. DOI: 10.1016/S1470-2045(14)70118-4. Epub 2014 Apr 14.

26. Radford J., McKay P., Peggs K. et al. Treatment pathways and resource use associated with the management of recurrent Hodgkin lymphoma after autologous stem cell transplantation. Presented at the 9th International Symposium on Hodgkin Lymphoma (ISHL), Cologne, Germany, October 2013.

27. Rini B.I., Halabi S., Rosenberg J.E. et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol. 2010 May 1; 28 (13): 2137-43. DOI: 10.1200/JCO.2009.26.5561. Epub 2010 Apr 5.

28. Robinson S.P., Sureda A., Canals C. et al. Reduced intensity conditioning allogeneic stem cell transplantation for Hodgkin's lymphoma: identification of prognostic factors predicting outcome. Haematologica. 2009 Feb; 94 (2): 230-8. DOI: 10.3324/haematol.13441. Epub 2008 Dec 9.

29. Sarina B., Castagna L., Farina L. et al. Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood. 2010; 115 (18): 3671-7.

30. Selby P., Patel P., Milan S. et al. ChlVPP combination chemotherapy for Hodgkin disease: long-term results. Br J Cancer. 1990; 2: 279-85.

31. Swinburn et al. Health state utilities for relapsed/refractory Hodgkin lymphoma (HL) and systemic anaplastic large-cell lymphoma (sALCL). Poster presented at the 17th Congress of the European Hematology Association (EHA). 2012 June 14-17; Amsterdam.

32. Younes A., Gopal A.K., Smith S.E. et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012 Jun 20; 30 (18): 2183-9. DOI: 10.1200/JCO.2011.38.0410. Epub 2012 Mar 26.