Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study

Ferhatoglu, Ferhat; Dogan, Izzet; KHANMAMMADOV, NİJAT; karabulut, senem; Bozbey, Hamza Ugur; Paksoy, Nail; TASTEKIN, DIDEM

doi:10.5505/tjo.2022.3756

Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study

Nail PAKSOY, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Tıbbi Onkoloji Anabilim Dalı, İstanbul, Türkiye)

Ferhat FERHATOĞLU, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Tıbbi Onkoloji Anabilim Dalı, İstanbul, Türkiye)

İzzet DOĞAN, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Tıbbi Onkoloji Anabilim Dalı, İstanbul, Türkiye)

Nijat KHANMAMMADOV, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Tıbbi Onkoloji Anabilim Dalı, İstanbul, Türkiye)

Hamza Ugur Bozbey, (İstanbul Yeniyüzyıl Üniversitesi, Tıp Fakültesi, Medikal Onkoloji Anabilim Dalı, İstanbul, Türkiye)

Senem KARABULUT, (İstanbul Üniversitesi, Onkoloji Enstitüsü, Tıbbi Onkoloji Anabilim Dalı, İstanbul, Türkiye)

Didem TAŞTEKİN (İstanbul Üniversitesi, Onkoloji Enstitüsü, Tıbbi Onkoloji Anabilim Dalı, İstanbul, Türkiye)

Türk Onkoloji Dergisi

0 0

Yıl: 2022 Cilt: 37 Sayı: 4 Sayfa Aralığı: 478 - 483 Metin Dili: İngilizce DOI: 10.5505/tjo.2022.3756 İndeks Tarihi: 26-05-2023

Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study

Öz:

OBJECTIVE Regorafenib, a multikinase inhibitor, is an approved third-line therapy for advanced gastrointestinal stromal tumors (GISTs). However, its routine clinical application is difficult due to the associated ad- verse events (AEs) reported by patients in the 1 st month, which leads to early discontinuation. In this study, we presented our experiences in toxicities management and the effectiveness of regorafenib in our institutional cancer center. METHODS Twenty-two patients treated with regorafenib as a third-line therapy for advanced GISTs were retro- spectively evaluated who had progressive disease after imatinib and sunitinib treatments. All patients received a full dose of 160 mg/day of regorafenib. RESULTS The average age of the patients was 49 years (range: 25-61 years), with a male preponderance (63.6%). The average follow-up time for the subjects was 114.2 months (16.2-210.3), while the median time of regorafenib using time was 7.7 months (1.9-29.1). The median overall survival (OS) of the patients was found as 10 months, while the 1-year OS rate was 38.3%. The median progression-free survival was found as 7.1 months. Regorafenib-related partial response was observed in 5 patients (22.7%), stable disease in 9 (40.9%), and progressive disease in 8 (36.4%). The disease control rate was 63.7%. Treat- ment-related grade 3/4 AEs were seen in ten (45.4%) patients. The most common AE was hand-foot skin reaction (5; 18.2%), followed by fatigue (3; 13.6%) and hypertension (2; 9.1%). Dose reductions were required in 7 patients (31.8%). The treatment was discontinued in a patient due to stroke. CONCLUSION Our results demonstrate promising activity and manageable side effects of regorafenib as third-line ther- apy of GIST in daily clinical practice in the Turkish population.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Miettinen M, Lasota J. Gastrointestinal stromal tu- mors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med 2006;130(10):1466–78.
2. Mucciarini C, Rossi G, Bertolini F, Valli R, Cirilli C, Rashid I, et al. Incidence and clinicopathologic fea- tures of gastrointestinal stromal tumors. A popula- tion-based study. BMC Cancer 2007;7:230.
3. Judson I, Bulusu R, Seddon B, Dangoor A, Wong N, Mudan S. UK clinical practice guidelines for the man- agement of gastrointestinal stromal tumours (GIST). Clin Sarcoma Res 2017;7(1):6.
4. Miettinen M, Lasota J. Gastrointestinal stromal tu- mors: pathology and prognosis at different sites. Semin Diagn Pathol 2006;23(2):70–83.
5. Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, et al. Kinase mutations and ima- tinib response in patients with metastatic gastrointesti- nal stromal tumor. J Clin Oncol 2003;21(23):4342–9
6. Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, et al. PDGFRA activating mu- tations in gastrointestinal stromal tumors. Science 2003;299(5607):708–10.
7. Casali PG, Abecassis N, Aro HT, Bauer S, Biagini R, Bielack S, et al; ESMO Guidelines Committee and EURACAN. Gastrointestinal stromal tumours: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018;29(Suppl 4):iv68–iv78.
8. Nannini M, Rizzo A, Nigro MC, Vincenzi B, Mazzocca A, Grignani G, et al. Standard versus personalized schedule of regorafenib in metastatic gastrointestinal stromal tumors: a retrospective, multicenter, real- world study. ESMO Open 2021;6(4):100222.
9. Foo T, Goldstein D, Segelov E, Shapiro J, Pavlakis N, Desai J, et al. The management of unresectable, ad- vanced gastrointestinal stromal tumours. Target Oncol 2022;17(2):95–110.
10. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointesti- nal stromal tumors. N Engl J Med 2002;347(7):472–80.
11. Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, et al. Phase III random- ized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol 2008;26(4):626–32.
12. Heinrich MC, Maki RG, Corless CL, Antonescu CR, Fletcher JA, Fletcher CD, et al. Sunitinib (SU) re- sponse in imatinib resistant (IM R) GIST correlates with KIT and PDGFRA mutation status. J Clin Oncol 2006;24(18 Suppl):9502.
13. Demetri GD, van Oosterom AT, Garrett CR, Black- stein ME, Shah MH, Verweij J, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006;368(9544):1329–38.
14. Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schütz G, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and onco- genic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 2011;129(1):245–55.
15. George S, Wang Q, Heinrich MC, Corless CL, Zhu M, Butryn ski JE, et al. Efficacy and safety of rego- rafenib in patients with metastatic and/or unre- sectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial. J Clin Oncol 2012;30(19):2401–7.
16. Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, et al. Efficacy and safety of rego- rafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an in- ternational, multicentre, randomised, placebo con- trolled, phase 3 trial. Lancet 2013;381(9863):295–302.
17. Chamberlain F, Farag S, Williams-Sharkey C, Colling- wood C, Chen L, Mansukhani S, et al. Toxicity man- agement of regorafenib in patients with gastro-intesti- nal stromal tumour (GIST) in a tertiary cancer centre. Clin Sarcoma Res 2020;10:1.
18. Schvartsman G, Wagner MJ, Amini B, Zobniw CM, Trinh VA, Barbo AG, et al. Treatment patterns, efficacy and toxicity of regorafenib in gastrointestinal stromal tumour patients. Sci Rep 2017;7(1):9519.
19. Nannini M, Nigro MC, Vincenzi B, Fumagalli E, Grig- nani G, D’Ambrosio L, et al. Personalization of rego- rafenib treatment in metastatic gastrointestinal stro- mal tumours in real-life clinical practice. Ther Adv Med Oncol 2017;9(12):731–9.
20. Jeffers M, Kappeler C, Kuss I, Beckmann G, Mehnert DH, Fredebohm J, et al. Broad spectr

APA	Paksoy N, Ferhatoglu F, Dogan I, KHANMAMMADOV N, Bozbey H, karabulut s, TASTEKIN D (2022). Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study. , 478 - 483. 10.5505/tjo.2022.3756
Chicago	Paksoy Nail,Ferhatoglu Ferhat,Dogan Izzet,KHANMAMMADOV NİJAT,Bozbey Hamza Ugur,karabulut senem,TASTEKIN DIDEM Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study. (2022): 478 - 483. 10.5505/tjo.2022.3756
MLA	Paksoy Nail,Ferhatoglu Ferhat,Dogan Izzet,KHANMAMMADOV NİJAT,Bozbey Hamza Ugur,karabulut senem,TASTEKIN DIDEM Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study. , 2022, ss.478 - 483. 10.5505/tjo.2022.3756
AMA	Paksoy N,Ferhatoglu F,Dogan I,KHANMAMMADOV N,Bozbey H,karabulut s,TASTEKIN D Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study. . 2022; 478 - 483. 10.5505/tjo.2022.3756
Vancouver	Paksoy N,Ferhatoglu F,Dogan I,KHANMAMMADOV N,Bozbey H,karabulut s,TASTEKIN D Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study. . 2022; 478 - 483. 10.5505/tjo.2022.3756
IEEE	Paksoy N,Ferhatoglu F,Dogan I,KHANMAMMADOV N,Bozbey H,karabulut s,TASTEKIN D "Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study." , ss.478 - 483, 2022. 10.5505/tjo.2022.3756
ISNAD	Paksoy, Nail vd. "Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study". (2022), 478-483. https://doi.org/10.5505/tjo.2022.3756

APA	Paksoy N, Ferhatoglu F, Dogan I, KHANMAMMADOV N, Bozbey H, karabulut s, TASTEKIN D (2022). Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study. Türk Onkoloji Dergisi, 37(4), 478 - 483. 10.5505/tjo.2022.3756
Chicago	Paksoy Nail,Ferhatoglu Ferhat,Dogan Izzet,KHANMAMMADOV NİJAT,Bozbey Hamza Ugur,karabulut senem,TASTEKIN DIDEM Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study. Türk Onkoloji Dergisi 37, no.4 (2022): 478 - 483. 10.5505/tjo.2022.3756
MLA	Paksoy Nail,Ferhatoglu Ferhat,Dogan Izzet,KHANMAMMADOV NİJAT,Bozbey Hamza Ugur,karabulut senem,TASTEKIN DIDEM Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study. Türk Onkoloji Dergisi, vol.37, no.4, 2022, ss.478 - 483. 10.5505/tjo.2022.3756
AMA	Paksoy N,Ferhatoglu F,Dogan I,KHANMAMMADOV N,Bozbey H,karabulut s,TASTEKIN D Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study. Türk Onkoloji Dergisi. 2022; 37(4): 478 - 483. 10.5505/tjo.2022.3756
Vancouver	Paksoy N,Ferhatoglu F,Dogan I,KHANMAMMADOV N,Bozbey H,karabulut s,TASTEKIN D Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study. Türk Onkoloji Dergisi. 2022; 37(4): 478 - 483. 10.5505/tjo.2022.3756
IEEE	Paksoy N,Ferhatoglu F,Dogan I,KHANMAMMADOV N,Bozbey H,karabulut s,TASTEKIN D "Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study." Türk Onkoloji Dergisi, 37, ss.478 - 483, 2022. 10.5505/tjo.2022.3756
ISNAD	Paksoy, Nail vd. "Toxicity Management and Effectiveness of Regorafenib in Advance GIST Patients: A Real-world Study". Türk Onkoloji Dergisi 37/4 (2022), 478-483. https://doi.org/10.5505/tjo.2022.3756