title: Evaluation of Novel Targeted Therapies in Aggressive Biology Sarcoma Patients after progression from US FDA approved Therapies.
abstract: Prognosis of patients with advanced sarcoma after progression from FDA approved therapies remains grim. In this study, clinical outcomes of 100 patients with advanced sarcoma who received treatment on novel targeted therapy trials were evaluated. Outcomes of interest included best response, clinical benefit rate, progression-free survival (PFS) and overall survival (OS). Median patient age was 48 years (range 14-80). Patients had received a median of 2 prior lines of systemic treatment. Phase I treatments were anti-VEGF-based (n = 45), mTOR inhibitor-based (n = 15), and anti-VEGF + mTOR inhibitor-based (n = 17) or involved other targets (n = 23). Best responses included partial response (n = 4) and stable disease (n = 57). Clinical benefit rate was 36% (95% confidence interval 27-46%). Median OS was 9.6 months (95% Confidence Interval 8.1-14.2); median PFS was 3.5 months (95% Confidence Interval 2.4-4.7). RMH prognostic score of 2 or 3 was associated with lower median OS (log-rank p-value < 0.0001) and PFS (log-rank p-value 0.0081). Receiving cytotoxic chemotherapy as part of phase I trial was also associated with shorter median OS (log-rank p-value 0.039). Patients with advanced sarcoma treated on phase I clinical trials had a clinical benefit rate of 36% and RMH score predicted survival.
authors.affiliation: Department of Investigational Cancer Therapeutics (A Phase I Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.|Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Subbiah
authors.affiliation: Division of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.affiliation: Department of Investigational Cancer Therapeutics (A Phase I Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: Muhammad Rizwan
authors.initials: MR
authors.lastname: Khawaja
authors.affiliation: Department of Investigational Cancer Therapeutics (A Phase I Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wagner
authors.affiliation: Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Investigational Cancer Therapeutics (A Phase I Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.affiliation: Department of Investigational Cancer Therapeutics (A Phase I Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.affiliation: Department of Investigational Cancer Therapeutics (A Phase I Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.affiliation: Department of Investigational Cancer Therapeutics (A Phase I Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: Sarina
authors.initials: S
authors.lastname: Piha-Paul
authors.affiliation: Department of Investigational Cancer Therapeutics (A Phase I Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Herzog
authors.affiliation: Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Ludwig
authors.affiliation: Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas.
authors.forename: Shreyaskumar
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas.
authors.forename: Vinod
authors.initials: V
authors.lastname: Ravi
authors.affiliation: Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Benjamin
authors.affiliation: Department of Investigational Cancer Therapeutics (A Phase I Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.affiliation: Department of Investigational Cancer Therapeutics (A Phase I Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston 77030, Texas, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D017321:Clinical Trials, Phase I as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D009362:Neoplasm Metastasis; D019233:Retreatment; D012509:Sarcoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers