Hans Gelderblom1, Ian R Judson2, Charlotte Benson2, Ofer Merimsky3, Giovanni Grignani4, Daniela Katz5, Klaus W Freivogel6, Dara Stein7, Minesh Jobanputra8, Arron Mungul9, Stephanie C Manson10, Roberta Sanfilippo11. 1. a Department of Medical Oncology , Leiden University Medical Centre , Leiden , the Netherlands. 2. b Sarcoma Unit , The Royal Marsden NHS Foundation Trust , London , UK. 3. c Unit of Bone and Soft Tissue Oncology , Tel-Aviv Sourasky Medical Center and Tel-Aviv University Sackler School of Medicine , Tel-Aviv , Israel. 4. d Divisione Oncologia Medica , Candiolo Cancer Institute - FPO I.R.C.C.S. , Candiolo , Italy. 5. e Hadassah-Hebrew University Medical Center , Jerusalem , Israel. 6. f United BioSource (Germany) GmbH , Loerrach , Germany. 7. g United BioSource Corporation , Quebec , Canada. 8. h bluebird bio , London , UK. 9. i Bristol-Myers Squibb , Uxbridge , UK. 10. j Novartis Oncology , East Hanover , NJ , USA. 11. k Adult Mesenchymal Tumor Medical Oncology Unit , Fondazione IRCCS Istituto Nazionale Tumori , Milan , Italy.
Abstract
BACKGROUND: A named patient program (NPP) was designed to provide patients with advanced soft-tissue sarcoma (aSTS) access to pazopanib, a multitargeted tyrosine kinase inhibitor. The SPIRE study was a retrospective chart review of participating patients. PATIENTS AND METHODS: Eligibility criteria for the NPP and SPIRE mirrored those of the pivotal phase-III study, PALETTE, which compared pazopanib with placebo in patients ≥18 years with aSTS and whose disease had progressed during or following prior chemotherapy or were otherwise unsuitable for chemotherapy. Outcomes of interest included treatment patterns, treatment duration, relative dose intensity, progression-free survival (PFS), overall survival (OS), clinical benefit rate, adverse events (AEs) and reasons for treatment discontinuation. RESULTS: A total of 211 patients were enrolled (median age 56 years; 60% female). Most patients received pazopanib in second- and third-line therapy (28.0% and 28.4%, respectively), followed by fourth line (19.0%) and ≥ fifth line (18.5%). The median duration of pazopanib treatment was 3.1 months (95% CI: 2.8-3.8), with a mean daily dose of 715 mg equating to 92% of recommended dose. Median OS was 11.1 months and clinical benefit rate was 46%. There was evidence of some clinical benefit across most histological subtypes. At study end, 40% of patients were alive and of these, 18% remained on pazopanib. Thirteen percent (13%) of patients discontinued pazopanib due to AEs. CONCLUSIONS: The SPIRE study demonstrated activity of pazopanib in heavily pretreated aSTS patients in a compassionate use setting. No new safety concerns were noted. Reassuringly, the relative dose intensity of pazopanib was 92%.
BACKGROUND: A named patient program (NPP) was designed to provide patients with advanced soft-tissue sarcoma (aSTS) access to pazopanib, a multitargeted tyrosine kinase inhibitor. The SPIRE study was a retrospective chart review of participating patients. PATIENTS AND METHODS: Eligibility criteria for the NPP and SPIRE mirrored those of the pivotal phase-III study, PALETTE, which compared pazopanib with placebo in patients ≥18 years with aSTS and whose disease had progressed during or following prior chemotherapy or were otherwise unsuitable for chemotherapy. Outcomes of interest included treatment patterns, treatment duration, relative dose intensity, progression-free survival (PFS), overall survival (OS), clinical benefit rate, adverse events (AEs) and reasons for treatment discontinuation. RESULTS: A total of 211 patients were enrolled (median age 56 years; 60% female). Most patients received pazopanib in second- and third-line therapy (28.0% and 28.4%, respectively), followed by fourth line (19.0%) and ≥ fifth line (18.5%). The median duration of pazopanib treatment was 3.1 months (95% CI: 2.8-3.8), with a mean daily dose of 715 mg equating to 92% of recommended dose. Median OS was 11.1 months and clinical benefit rate was 46%. There was evidence of some clinical benefit across most histological subtypes. At study end, 40% of patients were alive and of these, 18% remained on pazopanib. Thirteen percent (13%) of patients discontinued pazopanib due to AEs. CONCLUSIONS: The SPIRE study demonstrated activity of pazopanib in heavily pretreated aSTS patients in a compassionate use setting. No new safety concerns were noted. Reassuringly, the relative dose intensity of pazopanib was 92%.
Authors: Yitian Wang; Minxun Lu; Yong Zhou; Sisi Zhou; Xinzhu Yu; Fan Tang; Yi Luo; Wenli Zhang; Hong Duan; Li Min; Chongqi Tu Journal: Cancer Manag Res Date: 2020-07-01 Impact factor: 3.989