Sign up Calendar Latest Topics
 
 
 


Reply
  Author   Comment  
nosurrender

Avatar / Picture

Moderator
Registered:
Posts: 7,476
Reply with quote  #1 
[2121] Combination or sequential single agent for the treatment of metastatic breast cancer (MBC) patients (pts). Impact of further chemotherapy (CT) in overall survival (OS) in the Alamo registry.

Lluch A, Ruiz A, Martín M, Alba E, Pastor M, de la Haba J, Llombart A, Ramos M, Martínez del Prado P, Escudero MJ H C U Valencia, Valencia, Spain; IVO, Valencia, Spain; H C U San Carlos, Madrid, Spain; C H Virgen de la Victoria, Mlaga, Spain; H U La Fe, Valencia, Spain; C H Reina Sofa, Crdoba, Spain; H U Arnau de Vilanova, Lleida, Spain; C O Galicia, A Corua, Spain; H Basurto, Bilbao, Spain; GEICAM, Madrid, Spain

Introduction: Combinations can improve OS in MBC; however sequential single agent is sometimes preferred. In a recent report, pts receiving paclitaxel monotherapy in first line had a significantly worse OS if they were not receiving post study CT (PSC); no difference was seen in pts receiving paclitaxel+gemcitabine (Llombart, EBCC 2008). In this trial only 58% of pts received PSC.
Purpose: To assess, outside the context of a clinical trial, the amount of MBC pts receiving CT beyond first line, as well as the impact of combination use and further CT lines in their OS.
Methods: Alamo 1-2 is a breast cancer patient registry run by the GEICAM. 15482 pts diagnosed from 1990-1997 in 54 sites were included in the database. 4668 pts were stage IV; 778 (16.7%) metastatic at diagnosis and 3890 (83.3%) have had a recurrence.
Results: 3045 (65%) pts received CT in first line, 83% were combinations (with anthracyclines 42%, CMF 16%, taxane+anthracyclines 9.4% or +other agents 8%) and 16% were monotherapy. Among other variables studied, only previous treatment (in early stage) was influencing the choice of a combination (pts without previous CT received more combinations than pts receiving CMF, than pts receiving anthracyclines). Median survival for pts receiving single agent was significantly shorter compared to pts receiving combination, 16.2 and 21.85 months (m) respectively, HR=1.37 (IC 95%: 1.21-1.55; p<0.0001). Several covariates showed significant prognostic value in survival in the Cox multivariate model: monotherapy treatment in first line, anthracyclines pre-exposure, age > 65, negative hormonal receptor status, hepatic disease, Grade 3 and 3 disease sites. Half of the pts never received further CT after first line treatment. Only age and number of disease sites were influencing this decision in the Cox multivariate model. Median survival was 24.9 m in pts receiving further CT and 14.5 m in the ones not receiving it. In pts not receiving further CT, median OS was significantly shorter if they were treated with single agent in first line in comparison to those receiving previous combination: HR= 1.59 (IC 95%: 1.33-1.89; p< 0,00001). This difference was not significant in pts receiving further CT: HR= 1.15 (IC 95%: 0.97-1.37; p=0.101).
Conclusion: Our data show that only half of the MBC pts receive further CT after first line; they have longer survival. We found significant evidence that further CT is impacting the OS in pts treated with single agent in first line, but not in those receiving previous combination. Those facts should be taken into consideration when selecting single agent or a combination in first line.

__________________


WE WILL PREVAIL





nosurrender

Avatar / Picture

Moderator
Registered:
Posts: 7,476
Reply with quote  #2 
MORE HOPE FOR METS TX!

[2131] A multi-center phase II study of three doses of TAS-108 in postmenopausal women with advanced breast carcinoma following first or second line endocrine therapy.

Buzdar A, Tan-Chiu E, Schwartzberg L, Perez A, Ellis M, Garin A, Ingle J, Carlson R MD Anderson Cancer Center, Houston, TX; Florida Cancer Research Institute, Davie, FL; The West Clinic, Memphis, TN; Memorial Regional Hospital, Hollywood, FL; Washington University, St. Louis, MO; Russian Cancer Research Institute, Moscow, Russian Federation; Mayo Clinic, Rochester, MN; Stanford Cancer Center, Stanford, CA

Introduction: TAS-108 is an oral steroidal anti-estrogen agent that selectively inhibits ER and is mainly metabolized by CYP3A4. The purpose of this study is to investigate the efficacy and safety of TAS-108 administrated orally in three dose levels in patients with locally advanced, locally recurrent inoperable or metastatic breast carcinoma (BC) in four countries (USA, Russia, Mexico and Chile).
Methods: Postmenopausal women with confirmed ER and/or PgR positive BC who had previously responded to one or two standard endocrine therapies, with or without one prior chemotherapy were randomly assigned to three doses of TAS-108, 40 mg, 80 and 120 mg daily. Using a modified Panageas optimal two-stage trinomial design, the enrollment of 60 evaluable patients (first-stage: 19) was required to each individual dose group. Tumor response was assessed every 8 weeks according to RECIST criteria. Adverse events (AEs) were graded by CTC-AE v3.0.
Results: A total of 146 patients with mean age of 63 years old were enrolled with 61 patients in the 40 mg group and 66 in the 80 mg group. The 120 mg group was terminated at the end of stage 1 with 19 patients enrolled due to lack of efficacy. The mean duration of study treatment was 172 days for the 40 mg group and 160 days for the 80 mg group. Partial response (PR) was documented in 6 (10%) patients in the 40 mg group and 4 (6.7%) patients in the 80 mg group. The rate of disease stabilization (CR+PR+SD) reported by the investigators was 43% (95%CI, 31%,56%) in the 40 mg group and 45% (95%CI, 32%,58%) in the 80 mg group. Adjudicated clinical benefit (CR+PR+SD more than 24 wks) was observed in 22% of patients in the 40 mg group and 20% of patients in the 80 mg group. Clinical benefit was achieved in 25% of patients with 1 prior hormonal therapy and 15% of patients with more than one line of prior hormonal therapy. Median time to progression (TTP): 15 weeks for the 40 mg group and 15.9 weeks for the 80 mg group. Median duration of clinical benefit was 32 weeks in the 40 mg group and 64 weeks in the 80 mg group. In the 40/80/120 mg groups, the commonly reported treatment-related AEs included nausea (15%/11%/16%), fatigue (10%/11%/16%), headache (10%/6%/16%), hot flushes (10%/5%/32%), diarrhea (2%/6%/5%), constipation (3%/3%/5%), and arthralgia (2%/5%/11%). No endometrial cancer and treatment-related deaths occurred during the study.
Conclusions: TAS-108 has demonstrated anti-tumor activity in this population and was generally well tolerated. The 40 mg dose was chosen as the recommended dose for future clinical evaluation in patients with advanced breast cancer.



__________________


WE WILL PREVAIL





nosurrender

Avatar / Picture

Moderator
Registered:
Posts: 7,476
Reply with quote  #3 
MORE TO COME LATER.....

__________________


WE WILL PREVAIL





Previous Topic | Next Topic
Print
Reply

Quick Navigation:

Easily create a Forum Website with Website Toolbox.