Burcu CANER, Sibel OYUCU ORHAN, Büşra ASAN, Birol OCAK, Ahmet Bilgehan ŞAHİN, Adem DELİGÖNÜL, Erdem ÇUBUKÇU, Türkkan EVRENSEL

Metastatik Yumuşak Doku Sarkomlarında Trabektedin Kullanımının Retrospektif Değerlendirilmesi: Tek Merkez Deneyimi

etkilerinin değerlendirilmesi amaçlanmıştır. Sarkom tanısıyla trabektedin tedavisi alan 16 hastanın dosyaları retrospektif olarak tarandı. Hastaların demografik özellikleri, tedavi süreleri, tedavi yanıtları, ilaç yan etkileri kaydedildi. 16 hastanın 9’u erkek (%56,2), 7’si kadındı (%43,7). Trabektedin için medyan progresyonsuz sağkalım (progression-free survival, PFS) 2,9 ay, genel sağkalım (overall survival, OS) 6,7 ay saptandı. Sağkalım üzerine etkili olan tek faktör trabektedin tedavi sırası olarak belirlendi. Trabektedini 2. ya da 3.sıra tedavi olarak alan hastalar daha iyi PFS süresine (medyan PFS 10,3 aya karşı 1,6 ay, %95 GA: 0-21.9, p= 0.003) ve OS süresine (medyan 26,7 ay’a karşı 5,7 ay, %95 GA: 16.9-36.5, p= 0.003) sahipti. Sarkom çalışmalarında objektif yanıt değerlendirme kriteri olarak kullanılan büyüme modülasyon indeksi (growth modulation index, GMI) değeri 1,33’ün üzerinde olan hastaların PFS ve OS süreleri istatiksel anlamlı olarak daha iyiydi (medyan PFS 19,8 ay, p=0.002; medyan OS 26,7 ay, p=0.047). Tüm hastalarda yan etki gözlendi, grad 3/4 yan etkiler hematolojik yan etkiler %62,5 ve alanin aminotransferaz (ALT)/ aspartat aminotransferaz (AST) artışı %50 sıklıkta oldu. Çalışmada saptanan PFS, OS, yanıt oranları ve yan etkiler diğer çalışmalar ile benzer saptanmış, trabektedini 2.ve 3.sıra tedavi olarak alan hastaların ilaçtan daha fazla fayda gördüğü belirlenmiştir.

Anahtar Kelimeler:

metastatik sarkom, trabektedin, etkinlik, gerçek yaşam verisi

Retrospective Evaluation of Trabectedin Use in Metastatic Soft Tissue Sarcomas: A Single-Center Experience

This study aimed to evaluate the treatment responses, survival results, and drug side effects of patients treated with trabectedin for metastatic soft tissue sarcoma. The files of 16 patients who received trabectedin treatment with the diagnosis of sarcoma were reviewed retrospectively. Demographic characteristics of the patients, duration of treatment, response to treatment, and drug side effects were recorded. Of 16 patients, 9 (56.2%) were male and 7 (43.7%) were female. Median progression-free survival (PFS) for trabectedin was 2.9 months, and overall survival (OS) was 6.7 months. The only factor effective on survival was determined as trabectedin treatment line. Patients receiving trabectedin as second or third-line therapy had better PFS time (median PFS 10.3 vs 1.6 months, 95% CI: 0-21.9, p= 0.003) and OS time (median 26.7 vs 5.7 months, 95% CI: 16.9-36.5, p= 0.003). Patients with a growth modulation index (GMI) value above 1.33, which is used as an objective response evaluation metric in sarcoma studies, had statistically significantly better PFS and OS times (median PFS 19.8 months, p=0.002; median OS 26.7 months, p=0.047). Any grade side effects were observed in all patients, grade 3/4 side effects were hematological side effects in 62.5% and alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) increase in 50%. The PFS, OS, response rates and side effects detected in the study were found to be similar to other studies, and it was determined that the patients who received trabectedin as the second and third-line treatment benefited more from the drug.

Keywords:

metastatic sarcoma, trabectedin, efficacy, real-world data,

PDF

___

1. Verma S, Younus J, Stys-Norman D, Haynes AE, Blackstein M, Members of the Sarcoma Disease Site Group of Cancer Care Ontario’s Program in Evidence-Based Care. Meta-analysis of ifosfamide-based combination chemotherapy in advanced soft tissue sarcoma. Cancer Treat Rev. Haziran 2008;34(4):339-47.
2. Friedman D, Hu Z, Kolb EA, Gorfajn B, Scotto KW. Ecteinascidin-743 inhibits activated but not constitutive transcription. Cancer Research. 2002;62(12):3377-81.
3. Herrero AB, Martín-Castellanos C, Marco E, Gago F, Moreno S. Cross-Talk between Nucleotide Excision and Homologous Recombination DNA Repair Pathways in the Mechanism of Action of Antitumor Trabectedin. Cancer Res. 15 Ağustos 2006;66(16):8155-62.
4. Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, vd. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. JCO. 10 Mart 2016;34(8):786-93.
5. Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, vd. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 01 Eylül 2009;27(25):4188-96.
6. Penel N, Demetri GD, Blay JY, Cousin S, Maki RG, Chawla SP, vd. Growth modulation index as metric of clinical benefit assessment among advanced soft tissue sarcoma patients receiving trabectedin as a salvage therapy. Ann Oncol. Şubat 2013;24(2):537-42.
7. Le Cesne A, Blay JY, Judson I, Van Oosterom A, Verweij J, Radford J, vd. Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. J Clin Oncol. 20 Ocak 2005;23(3):576-84.
8. Patel S, von Mehren M, Reed DR, Kaiser P, Charlson J, Ryan CW, vd. Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Cancer. 01 Ağustos 2019;125(15):2610-20.
9. Le Cesne A, Blay J-Y, Cupissol D, Italiano A, Delcambre C, Penel N, vd. A randomized phase III trial comparing trabectedin to best supportive care in patients with pre-treated soft tissue sarcoma: T-SAR, a French Sarcoma Group trial. Annals of Oncology. 01 Ağustos 2021;32(8):1034-44.
10. Blay J-Y, Italiano A, Ray-Coquard I, Le Cesne A, Duffaud F, Rios M, vd. Long-term outcome and effect of maintenance therapy in patients with advanced sarcoma treated with trabectedin: an analysis of 181 patients of the French ATU compassionate use program. BMC Cancer. 06 Şubat 2013;13:64.
11. Samuels BL, Chawla S, Patel S, Mehren M von, Hamm J, Kaiser PE, vd. Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study†. Annals of Oncology. 01 Haziran 2013;24(6):1703-9.
12. Paz-Ares L, López-Pousa A, Poveda A, Balañá C, Ciruelos E, Bellmunt J, vd. Trabectedin in pre-treated patients with advanced or metastatic soft tissue sarcoma: a phase II study evaluating co-treatment with dexamethasone. Invest New Drugs. 01 Nisan 2012;30(2):729-40.
13. Jordan K, Jahn F, Jordan B, Kegel T, Müller-Tidow C, Rüssel J. Trabectedin: Supportive care strategies and safety profile. Critical Reviews in Oncology/Hematology. 01 Haziran 2015;94(3):279-90.
14. Grosso F, Jones RL, Demetri GD, Judson IR, Blay J-Y, Le Cesne A, vd. Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study. Lancet Oncol. Temmuz 2007;8(7):595-602.
15. Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, vd. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. Nisan 2015;16(4):406-16.
16. Chudgar NP, Brennan MF, Munhoz RR, Bucciarelli PR, Tan KS, D’Angelo SP, vd. Pulmonary metastasectomy with therapeutic intent for soft-tissue sarcoma. The Journal of Thoracic and Cardiovascular Surgery. 01 Temmuz 2017;154(1):319-330.e1.
17. van Geel AN, Pastorino U, Jauch KW, Judson IR, van Coevorden F, Buesa JM, vd. Surgical treatment of lung metastases: The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group study of 255 patients. Cancer. 15 Şubat 1996;77(4):675-82.