Abstract
Aim
Description of patient characteristics, effectiveness and safety in Turkish patients treated with pazopanib for metastatic soft tissue sarcoma (STS).
Patients and methods
This multicenter study is based on retrospective review of hospital medical records of patients (≥ 18 years) treated with pazopanib for non-adipocytic metastatic STS at 37 Oncology clinics across Turkey. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated with further analysis of data on the three most common histological subtypes (leiomyosarcoma [LMS], undifferentiated pleomorphic sarcoma [UPS], synovial sarcoma [SS]) in the cohort.
Results
Data of 552 adults (57.6% women, median age: 52 years) were analyzed. DCR and ORR were 43.1% and 30.8%, respectively. Median PFS was 6.7 months and OS was 13.8 months. For LMS, UPS and SS, median PFSs were 6.1, 5.9 and 7.53 months and median OSs were 15.03, 12.87 and 12.27 months, respectively. ECOG ≥ 2 was associated with poor PFS and OS. Liver metastasis was only a factor for progression. Second-line use of pazopanib (vs. front-line) was associated with better PFS, its use beyond third line predicted worse OS. Adverse events (AE) occurred in 82.7% of patients. Most common AEs were fatigue (58.3%) and anorexia (52.3%) which were graded as ≥ 3 in 8.2% and 7.4% of patients, respectively.
Conclusion
Pazopanib is effective and well-tolerated in treatment of non-adipocytic metastatic STS. Its earlier use (at second-line), good performance status may result in better outcomes. Worldwide scientific collaborations are important to gain knowledge on rarer STS subtypes by conducting studies in larger patient populations.
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Data availability
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy restrictions.
References
Alshamsan B, Badran A, Alshibany A et al (2021) Real-world outcome and prognostic factors of pazopanib in advanced soft tissue sarcoma. Cancer Manag Res 13:6755–6766. https://doi.org/10.2147/CMAR.S323499
Aykan MB, Keskin GS, Örnek E et al (2022) Efficacy of pazopanib in patients with pretreated advanced stage soft tissue sarcomas. Acta Oncologica Turcica 55:229–236. https://doi.org/10.5505/aot.2022.37108
Bajpai J, Mullapally SK, Kapoor A, Ghosh J, Rekhi B (2021) Pazopanib in metastatic soft tissue sarcomas: testing the waters in developing world. Indian J Cancer 58(3):365–370. https://doi.org/10.4103/ijc.IJC_314_19
Byar KL, Fredericks T (2022) Uterine leiomyosarcoma. J Adv Pract Oncol 13(1):70–76. https://doi.org/10.6004/jadpro.2022.13.1.6
Carroll C, Patel N, Gunsoy NB, Stirnadel-Farrant HA, Pokras S (2022) Meta-analysis of pazopanib and trabectedin effectiveness in previously treated metastatic synovial sarcoma (second-line setting and beyond). Future Oncol 18(32):3651–3665. https://doi.org/10.2217/fon-2022-0348
Gelderblom H, Judson IR, Benson C et al (2017) Treatment patterns and clinical outcomes with pazopanib in patients with advanced soft tissue sarcomas in a compassionate use setting: results of the SPIRE study. Acta Oncol 56(12):1769–1775. https://doi.org/10.1080/0284186X.2017.1332779
Gronchi A, Miah AB, Dei Tos AP et al (2021) Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 32(11):1348–1365. https://doi.org/10.1016/j.annonc.2021.07.006
Halim NA, Sayed RE, Alameh IA et al (2021) Safety and efficacy of pazopanib as a second-line treatment and beyond for soft tissue sarcomas: a real-life tertiary-center experience in the MENA region. Cancer Treat Res Commun 26:100275. https://doi.org/10.1016/j.ctarc.2020.100275
Huang PW, Chou WC, Shen WC et al (2018) Hand-foot skin reaction predicts treatment outcome of pazopanib in patients with metastatic soft tissue sarcoma: a multicenter study in the Asian population. Asia Pac J Clin Oncol 14(4):353–360. https://doi.org/10.1111/ajco.13029
Jonker CJ, Bakker E, Kurz X, Plueschke K (2022) Contribution of patient registries to regulatory decision making on rare diseases medicinal products in Europe. Front Pharmacol 13:924648. https://doi.org/10.3389/fphar.2022.924648
Karaağaç M, Sezgin Y, Eryılmaz MK, Araz M, Kaplan MA, Artaç M (2020) The real-life outcome of pazopanib in patients with advanced soft tissue sarcoma: a retrospective cross-sectional study of a Turkish cohort. J Oncol Pharm Pract 26(7):1657–1666. https://doi.org/10.1177/1078155220904138
Kasper B, Sleijfer S, Litière S et al (2014) Long-term responders and survivors on pazopanib for advanced soft tissue sarcomas: subanalysis of two European organisation for research and treatment of cancer (EORTC) clinical trials 62043 and 62072. Ann Oncol 25(3):719–724. https://doi.org/10.1093/annonc/mdt586
Koca S, Beşiroğlu M, Özçelik M et al (2021) Pazopanib for metastatic soft-tissue sarcoma: a multicenter retrospective study. J Oncol Pharm Pract 27(3):541–546. https://doi.org/10.1177/1078155220924075
Korn RL, Crowley JJ (2013) Overview: progression-free survival as an endpoint in clinical trials with solid tumors. Clin Cancer Res 19(10):2607–2612. https://doi.org/10.1158/1078-0432.CCR-12-2934
Kumar R, Knick VB, Rudolph SK et al (2007) Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol Cancer Ther 6(7):2012–2021. https://doi.org/10.1158/1535-7163.MCT-07-0193
Nakamura T, Matsumine A, Kawai A et al (2016) The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: a Japanese musculoskeletal oncology group (JMOG) study. Cancer 122(9):1408–1416. https://doi.org/10.1002/cncr.29961
Oh CR, Hong JY, Kim JH et al (2020) Real-world outcomes of pazopanib treatment in Korean patients with advanced soft tissue sarcoma: a multicenter retrospective cohort study. Target Oncol 15(4):485–493. https://doi.org/10.1007/s11523-020-00731-z
Pizzato M, Collatuzzo G, Santucci C et al (2023) Mortality patterns of soft-tissue sarcomas worldwide up to 2018, with predictions for 2025. Eur J Cancer Prev 32(1):71–80. https://doi.org/10.1097/CEJ.0000000000000768
Pokras S, Tseng WY, Espirito JL, Beeks A, Culver K, Nadler E (2022) Treatment patterns and outcomes in metastatic synovial sarcoma: a real-world study in the US oncology network. Future Oncol 18(32):3637–3650. https://doi.org/10.2217/fon-2022-0477
Ray-Coquard I, Collard O, Ducimetiere F et al (2017) Treatment patterns and survival in an exhaustive French cohort of pazopanib-eligible patients with metastatic soft tissue sarcoma (STS). BMC Cancer 17(1):111. https://doi.org/10.1186/s12885-017-3057-3
Sbaraglia M, Bellan E, Dei Tos AP (2021) The 2020 WHO classification of soft tissue tumours: news and perspectives. Pathologica 113(2):70–84. https://doi.org/10.32074/1591-951X-213
Schwartz LH, Litière S, de Vries E et al (2016) RECIST 1.1-update and clarification: from the RECIST committee. Eur J Cancer 62:132–137. https://doi.org/10.1016/j.ejca.2016.03.081
Seto T, Song MN, Trieu M et al (2019) Real-world experiences with pazopanib in patients with advanced soft tissue and bone sarcoma in Northern California. Med Sci (Basel) 7(3):48. https://doi.org/10.3390/medsci7030048
Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A (2023) Cancer statistics, 2023. CA Cancer J Clin 73(1):17–48. https://doi.org/10.3322/caac.21763
Sleijfer S, Ray-Coquard I, Papai Z et al (2009) Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol 27(19):3126–3132. https://doi.org/10.1200/JCO.2008.21.3223
van der Graaf WT, Blay JY, Chawla SP et al (2012) Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 379(9829):1879–1886. https://doi.org/10.1016/S0140-6736(12)60651-5
Yoo KH, Kim HS, Lee SJ et al (2015) Efficacy of pazopanib monotherapy in patients who had been heavily pretreated for metastatic soft tissue sarcoma: a retrospective case series. BMC Cancer 15:154. https://doi.org/10.1186/s12885-015-1160-x
Acknowledgements
We thank Dr. Idilhan Baloglu Ari and Sinan Ozgur Aydin for the supports.
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All authors contributed to the study conception and design. Material preparation and analysis were performed by AB. All authors contributed to data collection and substantial input to the conception and acquisition of the work. The first draft of the manuscript was written by A.B and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Bilici, A., Koca, S., Karaagac, M. et al. Real-world outcomes of pazopanib in metastatic soft tissue sarcoma: a retrospective Turkish oncology group (TOG) study. J Cancer Res Clin Oncol 149, 8243–8253 (2023). https://doi.org/10.1007/s00432-023-04766-3
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DOI: https://doi.org/10.1007/s00432-023-04766-3