Joaquim Bellmunt1, Francesc Pons2, Abigail Foreshew3, André P Fay4, Thomas Powles3, Camillo Porta5, Sergio Bracarda6, Megan E Lampron4, Linda Cerbone7, Cora N Sternberg7, Thomas E Hutson8, Toni K Choueiri8. 1. Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Hospital del Mar, Barcelona, Spain. Electronic address: joaquim_bellmunt@dfci.harvard.edu. 2. Hospital del Mar, Barcelona, Spain. 3. St Bartholomew's Hospital, London, UK. 4. Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 5. IRCCS San Matteo University Hospital Fundantion, Pavia, Italy. 6. Istituto Toscano Tumori, Arezzo, Italy. 7. San Camilo and Forlanini Hospitals, Rome, Italy. 8. GU Center of Excellence Texas Oncology, Dallas, TX.
Abstract
INTRODUCTION/ BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) in whom first-line therapies have failed might derive clinical benefit with sequential targeted agents. Limited data are available on the efficacy and toxicity of subsequent therapies after disease progression during pazopanib therapy. PATIENTS AND METHODS: Patients with mRCC who received subsequent systemic treatment after pazopanib treatment failure were identified across 7 institutions. Pazopanib was given as first-line therapy in 28 patients and after cytokines therapy in 7 patients. Clinical outcome and toxicity analyses of 2 sequential treatment options (anti-vascular endothelial growth factor [VEGF] or mammalian target of rapamycin inhibitor [mTORi]) is presented. RESULTS: Subsequent therapy was anti-VEGF in 22 patients and mTORi in 13. One patient who received bevacizumab and temsirolimus combination was excluded. VEGF-targeted therapies included sorafenib (n = 10), sunitinib (n = 3), bevacizumab (n = 2), cediranib (n = 4) and cabozantinib (n = 3). Patients treated with mTORi received everolimus. Median progression-free survival was 5.6 months from the start of subsequent therapy with anti-VEGF and 2.4 months with mTORi (P = .009). Overall survival (OS) was not significantly different (P = .68). Clinical benefit (including partial response and stable disease) on subsequent therapy was observed in 15 patients (64%) and 4 patients (31%) of anti-VEGF- and everolimus-treated patients, respectively (P = .021). CONCLUSION: In this retrospective study, targeting VEGF was an effective strategy after disease progression during pazopanib treatment, although OS was not different among patients treated with VEGF or mTORi.
INTRODUCTION/ BACKGROUND:Patients with metastatic renal cell carcinoma (mRCC) in whom first-line therapies have failed might derive clinical benefit with sequential targeted agents. Limited data are available on the efficacy and toxicity of subsequent therapies after disease progression during pazopanib therapy. PATIENTS AND METHODS: Patients with mRCC who received subsequent systemic treatment after pazopanib treatment failure were identified across 7 institutions. Pazopanib was given as first-line therapy in 28 patients and after cytokines therapy in 7 patients. Clinical outcome and toxicity analyses of 2 sequential treatment options (anti-vascular endothelial growth factor [VEGF] or mammalian target of rapamycin inhibitor [mTORi]) is presented. RESULTS: Subsequent therapy was anti-VEGF in 22 patients and mTORi in 13. One patient who received bevacizumab and temsirolimus combination was excluded. VEGF-targeted therapies included sorafenib (n = 10), sunitinib (n = 3), bevacizumab (n = 2), cediranib (n = 4) and cabozantinib (n = 3). Patients treated with mTORi received everolimus. Median progression-free survival was 5.6 months from the start of subsequent therapy with anti-VEGF and 2.4 months with mTORi (P = .009). Overall survival (OS) was not significantly different (P = .68). Clinical benefit (including partial response and stable disease) on subsequent therapy was observed in 15 patients (64%) and 4 patients (31%) of anti-VEGF- and everolimus-treated patients, respectively (P = .021). CONCLUSION: In this retrospective study, targeting VEGF was an effective strategy after disease progression during pazopanib treatment, although OS was not different among patients treated with VEGF or mTORi.
Authors: Hashem O Alsaab; Samaresh Sau; Rami M Alzhrani; Vino T Cheriyan; Lisa A Polin; Ulka Vaishampayan; Arun K Rishi; Arun K Iyer Journal: Biomaterials Date: 2018-08-30 Impact factor: 12.479