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Metastatik Kolorektal Kanserli Hastalarda Regorafenib ile Tek Merkez Gerçek Yaşam Deneyimi

Year 2020, Volume: 6 Issue: 1, 129 - 135, 01.01.2020

Abstract

Amaç: Rutin klinik uygulamada regorafenibin klinik yararını değerlendirmektir.Gereç ve Yöntemler: Ocak 2016 - Kasım 2018 tarihleri arasında regorafenib alan 45 metastatik kolorektal kanser hastasının verilerini retrospektif olarak değerlendirdik.Bulgular: Tüm hastaların ortanca yaşı 54 ve %66.7'si erkek hastaydı. Yirmi hastanın %44.4 performans durumu 2 iken, 25 hastada %55.6 0-1 idi. Otuz altı hastanın %80 primer tümörü rezekeydi ve hastaların %53.3'ünde KRAS mutasyonu vardı. Tüm hastalarda regorafenib başlangıç dozu 160 mg idi ve hastaların %28.9' una doz redüksiyonu uygulanmış olduğu görüldü. Regorafenib tedavisini hastaların %66.7'si 3. basamakta almış iken, %33.3ʼünde 4. basamak veya daha sonrasında almıştı. Regorafenib ile elde edilen en iyi yanıt progresif hastalık %46.7 ve stabil hastalık %35.6 idi. Ortanca progresyonsuz sağkalım 3.1 ay %95 CI: 2.2-4.0 ve genel sağkalım 6.4 ay %95 CI: 3.2-9.5 idi. Primer tümörün rezeksiyon durumu ve regorafenibin ≥ 4 basamak tedavi olarak kullanımı çok değişkenli analizde hem progresyonsuz sağkalım hem de genel sağkalım ile anlamlı şekilde ilişkiliydi.Sonuç: Regorafenib, bizim hastalarımızda da hem randomize kontrollü çalışmalarda hem de gerçek yaşam ortamında bildirilenlere benzer hayatta kalma süreleriyle ilişkiliydi ve genellikle iyi tolere edildi. Primer tümör rezeke edilen ve regorafenibi ≥ 4 basamak tedavi olarak kullanan hastalar istatistiksel olarak daha iyi progresyonsuz sağkalıma ve genel sağkalıma sahipti regorafenib 3. vs ≥ 4. basamak tedavi: PFS: 2.7 vs 4.6 ay, p:0.001; OS: 3.8 vs 11.4 ay, p:0.001, primeri rezeke vs rezeke olmayan: PFS: 3.8 vs 1.6 ay, p: 0.006; OS: 6.1 vs 3.1 ay, p: 0.018 . Primer tümörü rezeke edilen hastalarda regorafenib ile daha iyi sağkalım oluşunu açıklamak ve bu bilgiyi doğrulamak için başka çalışmalara ihtiyaç vardır

References

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6):394-424.
  • Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouché O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D. CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381(9863):303-12.
  • Li J, Qin S, Xu R, Yau TC, Ma B, Pan H, Xu J, Bai Y, Chi Y, Wang L, Yeh KH, Bi F, Cheng Y, Le AT, Lin JK, Liu T, Ma D, Kappeler C, Kalmus J, Kim TW. CONCUR Investigators. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): A randomised, double-blind, placebo- controlled, phase 3 trial. Lancet Oncol 2015; 16(6):619- 29.
  • Van Cutsem E, Martinelli E, Cascinu S, Sobrero A, Banzi M, Seitz JF, Barone C, Ychou M, Peeters M, Brenner B, Hofheinz RD, Maiello E, André T, Spallanzani A, Garcia-Carbonero R, Arriaga YE, Verma U, Grothey A, Kappeler C, Miriyala A, Kalmus J, Falcone A, Zaniboni A. Regorafenib for patients with metastatic colorectal cancer who progressed after standard therapy: Results of the large, single-arm, open-label phase IIIb CONSIGN study. Oncologist 2019; 24(2):185-92.
  • Adenis A, de la Fouchardiere C, Paule B, Burtin P, Tougeron D, Wallet J, Dourthe LM, Etienne PL, Mineur L, Clisant S, Phelip JM, Kramar A, Andre T. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: Results from a multicenter study (REBECCA) nested within a compassionate use program. BMC Cancer 2016; 16:412.
  • Aljubran A, Elshenawy MA, Kandil M, Zahir MN, Shaheen A, Gad A, Alshaer O, Alzahrani A, Eldali A, Bazarbashi S. Efficacy of Regorafenib in Metastatic Colorectal Cancer: A Multi-institutional Retrospective Study. Clin Med Insights Oncol 2019; 13:1179554918825447.
  • Unseld M, Filip M, Seirl S, Gleiss A, Bianconi D, Kieler M, Demyanets S, Scheithauer W, Zielinski C, Prager G. Regorafenib therapy in metastatic colorectal cancer patients: Markers and outcome in an actual clinical setting. Neoplasma 2018; 65(4):599-603.
  • Gotfrit J, Vickers M, Sud S, Asmis T, Cripps C, Goel R, Hsu T, Jonker D, Goodwin R. Real-life treatment of metastatic colorectal cancer with regorafenib: A single- centre review. Curr Oncol 2017; 24(4):234-9.
  • Calcagno F, Lenoble S, Lakkis Z, Nguyen T, Limat S, Borg C, Jary M, Kim S, Nerich V. Efficacy, safety and cost of regorafenib in patients with metastatic colorectal cancer in french clinical practice. Clin Med Insights Oncol 2016; 10:59-66.
  • Ramaswamy A, Ostwal V, Pande N, Sharma A, Patil S, Thippeswamy R, Ghadyalpatil N, Roy R, Peshwe H, Poladia B, Rajamanickam D, Rangarajan B, Neelesh Reddy PR, Pandita V, Mukherjee A, Thoke A, Sarkar A, Satish CT, Shashidara H, Banavali SD. Practice patterns and outcomes with the use of regorafenib in metastatic colorectal cancer: Results from the regorafenib in metastatic colorectal cancer- An Indian exploratory analysis study. South Asian J Cancer 2019; 8(1):22-6.
  • Giampieri R, Prete MD, Prochilo T, Puzzoni M, Pusceddu V, Pani F, Maccaroni E, Mascia R, Baleani MG, Meletani T, Berardi R, Lanzillo AM, Mariotti S, Zaniboni A, Cascinu S, Scartozzi M. Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis. Sci Rep 2017; 7:45703.
  • Osawa H. Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer. Mol Clin Oncol 2017; 6(3):365-72.
  • Yoon SE, Lee SJ, Lee J, Park SH, Park JO, Lim HY, Kang WK, Park YS, Kim ST. The use of regorafenib for patients with refractory metastatic colorectal cancer in clinical practice. Onco Targets Ther 2018; 12:225-31.
  • Yamaguchi K, Komatsu Y, Satoh T, Uetake H, Yoshino T, Nishida T, Yamazaki N, Takikawa H, Morimoto T, Chosa M, Sunaya T, Hamada Y, Muro K, Sugihara K. Large-Scale, prospective observational study of regorafenib in japanese patients with metastatic colorectal cancer in a real-world clinical setting. Oncologist 2019; 24(7):e450-e457.
  • Bekaii-Saab TS, Fs O, Anderson DM, Ahn DH, Boland PM, Ciombor KK. Regorafenib dose optimization study (ReDOS): Randomized phase II trial to evaluate dosing strategies for regorafenib in refractory metastatic colorectal cancer (mCRC) - An ACCRU Network study. J Clin Oncol 2018; 36 Suppl:611.

Single Center Real Life Experience with Regorafenib in Patients with Metastatic Colorectal Cancer

Year 2020, Volume: 6 Issue: 1, 129 - 135, 01.01.2020

Abstract

Objective: To evaluate the clinical benefit of regorafenib in routine clinical practice.Material and Methods: We retrospectively evaluated the data of 45 metastatic colorectal cancer mCRC patients who received regorafenib between January 2016 and November 2018.Results: The median age of all patients was 54 years, and 66.7% of the patients were male. Performance status of 20 patients 44.4% was 2, whereas in 25 patients 55.6% it was 0-1. Thirty-six patients 80% were performed primary tumor resection and KRAS mutation was detected in 53.3% of patients. Regorafenib was started at a dose of 160 mg in all patients, and a dose reduction was observed in 28.9% of patients. Line of regorafenib treatment was 3rd in 66.7% of patients, whereas in 33.3% of patients it was ≥ 4th. Best response was progressive disease 46.7% and stable disease 35.6% . The median progression free survival PFS was 3.1 months 95% CI: 2.2-4.0 and overall survival OS was 6.4 months 95% CI: 3.2-9.5 . Primary tumor resection status and using regorafenib ≥ 4 treatment line were significantly associated with both PFS and OS in multivariate analysis. Conclusion: Regorafenib was associated with survival durations similar to those reported in both randomized controlled trials and in the real-life setting, and was generally well tolerated. Patients who had primary tumor resected and using regorafenib as the ≥ 4th treatment line primary resected vs nonresected: PFS: 3.8 vs. 1.6 months, p: 0.006; OS: 6.1 vs. 3.1 months, p: 0.018, 3rd vs. 4th or more: PFS: 2.7 vs. 4.6 months, p:0.001; OS: 3.8 vs. 11.4 months, p:0.001 were associated with better PFS and OS. However, in order to explain the better survival with regorafenib in patients with primary tumor resected, this information must be confirmed with further studies

References

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6):394-424.
  • Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouché O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D. CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381(9863):303-12.
  • Li J, Qin S, Xu R, Yau TC, Ma B, Pan H, Xu J, Bai Y, Chi Y, Wang L, Yeh KH, Bi F, Cheng Y, Le AT, Lin JK, Liu T, Ma D, Kappeler C, Kalmus J, Kim TW. CONCUR Investigators. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): A randomised, double-blind, placebo- controlled, phase 3 trial. Lancet Oncol 2015; 16(6):619- 29.
  • Van Cutsem E, Martinelli E, Cascinu S, Sobrero A, Banzi M, Seitz JF, Barone C, Ychou M, Peeters M, Brenner B, Hofheinz RD, Maiello E, André T, Spallanzani A, Garcia-Carbonero R, Arriaga YE, Verma U, Grothey A, Kappeler C, Miriyala A, Kalmus J, Falcone A, Zaniboni A. Regorafenib for patients with metastatic colorectal cancer who progressed after standard therapy: Results of the large, single-arm, open-label phase IIIb CONSIGN study. Oncologist 2019; 24(2):185-92.
  • Adenis A, de la Fouchardiere C, Paule B, Burtin P, Tougeron D, Wallet J, Dourthe LM, Etienne PL, Mineur L, Clisant S, Phelip JM, Kramar A, Andre T. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: Results from a multicenter study (REBECCA) nested within a compassionate use program. BMC Cancer 2016; 16:412.
  • Aljubran A, Elshenawy MA, Kandil M, Zahir MN, Shaheen A, Gad A, Alshaer O, Alzahrani A, Eldali A, Bazarbashi S. Efficacy of Regorafenib in Metastatic Colorectal Cancer: A Multi-institutional Retrospective Study. Clin Med Insights Oncol 2019; 13:1179554918825447.
  • Unseld M, Filip M, Seirl S, Gleiss A, Bianconi D, Kieler M, Demyanets S, Scheithauer W, Zielinski C, Prager G. Regorafenib therapy in metastatic colorectal cancer patients: Markers and outcome in an actual clinical setting. Neoplasma 2018; 65(4):599-603.
  • Gotfrit J, Vickers M, Sud S, Asmis T, Cripps C, Goel R, Hsu T, Jonker D, Goodwin R. Real-life treatment of metastatic colorectal cancer with regorafenib: A single- centre review. Curr Oncol 2017; 24(4):234-9.
  • Calcagno F, Lenoble S, Lakkis Z, Nguyen T, Limat S, Borg C, Jary M, Kim S, Nerich V. Efficacy, safety and cost of regorafenib in patients with metastatic colorectal cancer in french clinical practice. Clin Med Insights Oncol 2016; 10:59-66.
  • Ramaswamy A, Ostwal V, Pande N, Sharma A, Patil S, Thippeswamy R, Ghadyalpatil N, Roy R, Peshwe H, Poladia B, Rajamanickam D, Rangarajan B, Neelesh Reddy PR, Pandita V, Mukherjee A, Thoke A, Sarkar A, Satish CT, Shashidara H, Banavali SD. Practice patterns and outcomes with the use of regorafenib in metastatic colorectal cancer: Results from the regorafenib in metastatic colorectal cancer- An Indian exploratory analysis study. South Asian J Cancer 2019; 8(1):22-6.
  • Giampieri R, Prete MD, Prochilo T, Puzzoni M, Pusceddu V, Pani F, Maccaroni E, Mascia R, Baleani MG, Meletani T, Berardi R, Lanzillo AM, Mariotti S, Zaniboni A, Cascinu S, Scartozzi M. Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis. Sci Rep 2017; 7:45703.
  • Osawa H. Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer. Mol Clin Oncol 2017; 6(3):365-72.
  • Yoon SE, Lee SJ, Lee J, Park SH, Park JO, Lim HY, Kang WK, Park YS, Kim ST. The use of regorafenib for patients with refractory metastatic colorectal cancer in clinical practice. Onco Targets Ther 2018; 12:225-31.
  • Yamaguchi K, Komatsu Y, Satoh T, Uetake H, Yoshino T, Nishida T, Yamazaki N, Takikawa H, Morimoto T, Chosa M, Sunaya T, Hamada Y, Muro K, Sugihara K. Large-Scale, prospective observational study of regorafenib in japanese patients with metastatic colorectal cancer in a real-world clinical setting. Oncologist 2019; 24(7):e450-e457.
  • Bekaii-Saab TS, Fs O, Anderson DM, Ahn DH, Boland PM, Ciombor KK. Regorafenib dose optimization study (ReDOS): Randomized phase II trial to evaluate dosing strategies for regorafenib in refractory metastatic colorectal cancer (mCRC) - An ACCRU Network study. J Clin Oncol 2018; 36 Suppl:611.
There are 15 citations in total.

Details

Primary Language English
Journal Section Research Article
Authors

Melek Karakurt Eryılmaz This is me

Mustafa Karaagac This is me

Murat Araz This is me

Fatma Yalcın Musrı This is me

Mehmet Artac This is me

Publication Date January 1, 2020
Published in Issue Year 2020 Volume: 6 Issue: 1

Cite

Vancouver Karakurt Eryılmaz M, Karaagac M, Araz M, Yalcın Musrı F, Artac M. Single Center Real Life Experience with Regorafenib in Patients with Metastatic Colorectal Cancer. Akd Med J. 2020;6(1):129-35.