Clinical case of the use of oral metronomic vinorelbin in patient with metastatic Her2 negative breast cancer

Endocrine therapy in combination with inhibitors of cyclin-dependent kinases 4/6 in first lines is the current standard of treatment of metastatic ER positive Her2 negative breast cancer. After progression on several lines of endocrine therapy according to current principles we apply sequential lines of monochemotherapy. If possible non-toxic agents are prefered in order to maintain high quality of life. The special role in this context may play oral agents, when regular visits in clinic and intravenous injection are not needed. The efficacy of oral vinorelbine is well explored, unfortunately the standard dosage regimen сan have quite high especially hematologic toxicity. The metronomic dosing regimen is believed to be as effective as the standard, but is less toxic. In addition, the anti-angiogenic properties of the metronomic mode are described. Taking into account the increasing use of combination of endocrine therapy with CDK4/6 inhibitors in first treatment lines, it is extremely important to study the efficacy and tolerability of various regimens and drugs after progression on combined endocrine therapy. In this article, we represent a clinical case of the use of oral vinorelbine in the metronomic mode in the patient after progression on combination of fulvestrant and palbociclib. Long-term disease control with satisfactory quality of life has been demonstrated.

1. Cardoso F., Costa A., Norton L., Senkus E., Aapro M., André F. et al. ESOESMO 2nd international consensus guidelines for advanced breast cancer (ABC2). Ann Oncol. 2014;25(10):1871–1888. https://doi.org/10.1093/annonc/mdu385.

2. Cardoso F., Costa A., Norton L., Senkus E., Aapro M., André F. et al. ESOESMO 2nd international consensus guidelines for advanced breast cancer (ABC2). Breast. 2014;23(5):489–502. https://doi.org/10.1016/j.breast.2014.08.009.

3. Cardoso F., Paluch-Shimon S., Senkus E., Curigliano G., Aapro M.S., André F. et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020;31(12):1623–1649. https://doi.org/10.1016/j.annonc.2020.09.010.

4. Findlay M., Von Minckwitz G., Wardley A. Effective oral chemotherapy for breast cancer: pillars of strength. Ann Oncol. 2008;19(2):212–222. https://doi.org/10.1093/annonc/mdm285.

5. Liu G., Franssen E., Fitch M.I., Warner E. Patient preference for oral versus intravenous рalliative chemotherapy. J Clin Oncol. 1997;15(1):110–115. https://doi.org/10.1200/JCO.1997.15.1.110.

6. Khisamov A.A. Oral vinorelbine as monotherapy in treatment of advanced breast cancer. Literature review. Zlokachestvennye opukholi = Malignant Tumours. 2016;(2):43–48. (In Russ.) https://doi.org/10.18027/2224-5057-2016-2-43-48.

7. Fumoleau P., Delgado D.M., Delozier T., Monnier A., Gil Delgado M.A., Kerbrat P. et al. Phase II trial of weekly intravenous vinorelbine in first line advanced breast cancer chemotherapy. J Clin Oncol. 1993;11(7):1245– 1252. https://doi.org/10.1200/JCO.1993.11.7.1245.

8. García-Conde J., Lluch A., Martin M., Casado A., Gervasio H., De Oliveira C. et al. Phase II trial of weekly IV vinorelbine in first-line advanced breast cancer chemotherapy. Ann Oncol. 1994;5(9):854–857. https://doi.org/10.1093/oxfordjournals.annonc.a059019.

9. Freyer G., Delozier T., Lichinister M., Gedouin D., Bougnoux P., His P. et al. Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol. 2003;21(1):35–40. https://doi.org/10.1200/jco.2003.09.057.

10. Amadori D., Koralewski P., Tekiela A., Ruiz Simon A., Llombart A., Sommer H. et al. Efficacy and safety of navelbine oral (NVBO) in first line metastatic breast cancer (MBC). Eur J Cancer. 2001;37(Suppl. 6):S195. https://doi.org/10.1016/S0959-8049(01)81205-3.

11. Pluschnig U., Bartsch R., Gampenrieder S., Wensel C., Altorjai G., Gnant M. et al. Oral vinorelbine in metastatic breast cancer: the Vienna experience. Ann Oncol. 2008;19(Suppl. 8). Available at: https://www.researchgate.net/publication/298343794_ORAL_VINORELBINE_IN_METASTATIC_BREAST_CANCER_THE_VIENNA_EXPERIENCE.

12. Blancas I., Morales S., Diaz N., Barnadas A., Gonzalvez M.L., del Barco S. et al. Efficacy and safety of oral vinorelbine (NVBO) in first- or second-line metastatic breast cancer (MBC). J Clin Oncol. 2010;28(15S):1090. https://doi.org/10.1200/jco.2010.28.15_suppl.1090.

13. André N., Carré M., Pasquier E. Metronomics: towards personalized chemotherapy? Nat Rev Clin Oncol. 2014;11(7):413–431. https://doi.org/10.1038/nrclinonc.2014.89.

14. Bocci G., Francia G., Man S., Lawler J., Kerbel R.S. Thrombospondin 1, a mediator of the antiangiogenic effects of low-dose metronomic chemotherapy. Proc Natl Acad Sci USA. 2003;100:12917-12922. https://doi.org/10.1073/pnas.2135406100.

15. Cazzaniga M.E., Camerini A., Addeo R., Nolè F., Munzone E., Collovà E. et al. Metronomic oral vinorelbine in advanced breast cancer and non-smallcell lung cancer: current status and future development. Future Oncol. 2016;12(3):373–387. https://doi.org/10.2217/fon.15.306.

16. Briasoulis E., Aravantinos G., Kouvatseas G., Pappas P., Biziota E., Sainis I. et al. Dose selection trial of metronomic oral vinorelbine monotherapy in patients with metastatic cancer: a hellenic cooperative oncology group clinical translational study. BMC Cancer. 2013;13:263. https://doi.org/10.1186/1471-2407-13-263.

17. Addeo R., Sgambato A., Cennamo G., Montella L., Faiola V., Abbruzzese A. et al. Low-dose metronomic oral administration of vinorelbine in the 1stline treatment of elderly patients with metastatic breast cancer. Clin Breast Cancer. 2010;10(4):301–306. https://doi.org/10.3816/CBC.2010.n.039.

18. De Iuliis F., Salerno G., Taglieri L., Lanza R., Scarpa S. On and off metronomic oral vinorelbine in elderly women with advanced breast cancer. Tumori. 2015;101(1):30–35. https://doi.org/10.5301/tj.5000207.

19. Munzone E., Colleoni M. Clinical overview of metronomic chemotherapy in breast сancer. Nat Rev Clin Oncol. 2015;12(11):631–644. https://doi.org/10.1038/nrclinonc.2015.131.

20. Mansour M., Mourad С. Phase II Study of Single Agent Oral Vinorelbine (OV) as First-Line Chemotherapy (CT) in Patients (PTS) with HER-2 Negative Metastatic Breast Cancer (MBC): A Single Center Experience. Ann Oncol. 2012; 23(Suppl. 9):ix138. https://doi.org/10.1016/S0923-7534(20)32958-6.

21. Cardoso F., Colleoni M., Di Leo A., Francia G., Gennari A., Gligorov J., Llombart A. Oral chemotherapy in advanced breast cancer: expert perspectives on its role in clinical practice. Cancer Treatment Communications. 2016;6(Suppl. 1):S1-S10. https://doi.org/10.1016/S2213-0896(16)06001-1.

22. Wang L., Gao S., Li D., Ran X., Sheng Z., Wu Z., Yang X. CDK4/6 inhibitors plus endocrine therapy improve overall survival in advanced HR+/HER2− breast cancer: A meta-analysis of randomized controlled trials. Breast J. 2020;26(7):1439–1443. https://doi.org/10.1111/tbj.13703.

23. Giuliano M., Schettini F., Rognoni C., Milani M., Jerusalem G., Bachelot T. et al. Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis. Lancet Oncol. 2019;20(10):1360–1369. https://doi.org/10.1016/S1470-2045(19)30420-6.

24. Princic N., Aizer A., Tang D.H., Smith D.M., Johnson W., Bardia A. Predictors of systemic therapy sequences following a CDK 4/6 inhibitor-based regimen in post-menopausal women with hormone receptor positive, HEGFR2 negative metastatic breast cancer. Curr Med Res Opin. 2019;35(1):73–80. https://doi.org/10.1080/03007995.2018.1519500.

25. Mougalian S.S., Feinberg B.A., Wang E., Alexis K., Chatterjee D., Knoth R.S. et al. Observational study of clinical outcomes of eribulin mesylate in metastatic breast cancer after cyclin-dependent kinase 4/6 inhibitor therapy. Future Oncol. 2019;15(34):3935–3944. https://doi.org/10.2217/fon-2019-0537.