title: Survival of patients with metastatic leiomyosarcoma: the MD Anderson Clinical Center for targeted therapy experience.
abstract: Advanced stage leiomyosarcoma (LMS) is incurable with current systemic antitumor therapies. Therefore, there is clinical interest in exploring novel therapeutic regimens to treat LMS. We reviewed the medical records of 75 consecutive patients with histologically confirmed metastatic LMS, who had been referred to the Clinical Center for Targeted Therapy at MD Anderson Cancer Center. To lay the foundation for potential phase I trials for the treatment of advanced LMS, we analyzed tumor response and survival outcome data. The frequent hotspot gene aberrations that we observed were the TP53 mutation (65%) and RB1 loss/mutation (45%) detected by Sequenom or next-generation sequencing. Among patients treated with gene aberration-related phase I trial therapy, the median progression-free survival was 5.8 months and the median overall survival was 15.9 months, significantly better than in patients without therapy (1.9 months, P = 0.001; and 8.7 months, P = 0.013, respectively). Independent risk factors that predicted shorter overall survival included hemoglobin <10 g/dL, body mass index <30 kg/m2, serum albumin <3.5 g/dL, and neutrophil above upper limit of normal. The median survivals were 19.9, 7.6, and 0.9 months for patients with 0, 1 or 2, and ≥3 of the above risk factors, respectively (P < 0.001). A prognostic scoring system that included four independent risk factors might predict survival in patients with metastatic LMS who were treated in a phase I trial. Gene aberration-related therapies led to significantly better clinical benefits, supporting that further exploration with novel mechanism-driven therapeutic regimens is warranted.
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Naiyi
authors.initials: N
authors.lastname: Shi
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Vivek
authors.initials: V
authors.lastname: Subbiah
authors.affiliation: Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Dejka M
authors.initials: DM
authors.lastname: Araujo
authors.affiliation: Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Shreyaskumar R
authors.initials: SR
authors.lastname: Patel
authors.affiliation: Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Ludwig
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Lois M
authors.initials: LM
authors.lastname: Ramondetta
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Levenback
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Pedro T
authors.initials: PT
authors.lastname: Ramirez
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sarina A
authors.initials: SA
authors.lastname: Piha-Paul
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: David
authors.initials: D
authors.lastname: Hong
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Karp
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D007890:Leiomyosarcoma / Q000150:complications / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D013781:Texas; D016896:Treatment Outcome
keywords: gene aberration-related therapy; leiomyosarcoma; overall survival; phase I clinical trial; prognostic scoring model