Toxicities of Chemotherapy Regimens used in Early Breast Cancer

Transcription

1 Toxicities of Chemotherapy Regimens used in Early Breast Cancer CERCIT Workshop February 17, 2012 Carlos H Barcenas, M.D., M.S. Fellow Hematology-Oncology MD Anderson Cancer Center CERCIT Scholar

2 Outline 1. Background 2. Data Sources 3. Methods 4. Results 5. Discussion

3 Siegel et al, CA Cancer J Clin 2012

4 Background Treatment of Breast Cancer Multidisciplinary approach: surgery, radiation therapy, chemotherapy, hormonal treatment, targeted therapy, or combination of the above Treatment plan depends on several factors, such as stage, tumor biology, receptors Other factors that can influence treatment: age, comorbid conditions, personal preference

5 Chemotherapy Benefits in Breast Cancer Chemotherapy reduces breast cancer (BC) recurrence and mortality Shown in randomized control trials and metaanalysis. 6 months of an anthracycline based chemotherapy reduces the annual BC death rate by 38% for women younger than 50 years of age and by 20% for those of age years. Early Breast Cancer Trialists Group (EBCTG), Lancet 2005

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7 Regimens Used in HER2-Negative Early Breast Cancer Non-anthracycline: CMF x6: Cyclophosphamide + Methotrexate + 5-FU TC x4: Docetaxel (Taxotere) + C Anthracycline based: TAC x6: T + Doxorubicin (Adriamycin) + C AC x4 weekly Paclitaxel x12 weeks; AC x4 T Dose-dense (q14 days) AC x4 Paclitaxel x4 Dose-dense A-T-C: A x4 Paclitaxel x4 C x4 FEC (Epirubicin) T; FEC Paclitaxel Non- taxane: ACx4; FACx6; CAFx6; ECx8; CEFx6

8 Anthracycline-based Regimen vs. CMF Direct comparison of 17 trials of CMF-based vs. anthracycline-containing regimens were made (15,000 women; 4,000 deaths). Anthracycline-containing polychemotherapy produced greater beneficial effects on recurrence and breast cancer mortality than CMF. A minimum of 4 cycles of an anthracyclinebased regimen is considered standard. Clarke M, Ann Oncology Jones SE, et al, JCO. 2006

9 Cardiac damage is irreversible Damage extent depends on: cumulative dose, drug combinations, patient factors Incidence of CHF increases with cumulative dose >500 mg/m2 of doxorubicin The risk of developing CHF with standard doses is between 1.6% and 2.1%

10 Shift in Pattern of Care Giordano SH, Lin Y, Kuo Y, et al: Anthracyline use among women with breast cancer. ASCO Meeting Abstracts 29:Abstract 1019, 2011 In pts with age >65 yrs, anthracycline (A) use peaked in 2005 at 68% and decreased to 32% by 2008; taxane (T) use increased from 12% in 2005 to 51% in In pts <65 yrs, A use peaked in 2004 at 86% and decreased to 49% in 2008; T use increased from 9% in 2004 to 46% in 2008.

11 SAN ANTONIO BREAST CANCER SYMPOSIUM 2005 Slamon et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients: BCIRG 006 study. Jones et al. Final analysis: TC (docetaxel/ cyclophosphamide, 4 cycles) has a superior disease-free survival compared to standard AC (doxorubicin/ cyclophosphamide) in 1016 women with early stage breast cancer.

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13 The addition of 1 yr of adjuvant trastuzumab significantly improved DFS and OS among women with HER2- positive breast cancer. The risk benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia.

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15 Phase III Clinical Trial TAC vs. TC Estimated Enrollment: 2000 Study Start Date: May 2007 Estimated Study Completion Date: May 2015

16 Toxicities of Taxanes Myelosuppression (neutropenia) Hypersensitivity reactions Fluid retention (Docetaxel) Peripheral neuropathy (more Paclitaxel) Mucositis Skin rash Cancer Chemotherapy Drug Manual 2011 (Chu and DeVita)

17 Objective To compare differences in toxicities between anthracycline-based and taxane-based breast cancer chemotherapy regimens, using hospitalization information from population-based databases.

18 Data Sources SEER- Medicare database Surveillance, Epidemiology, and End Results (SEER) Program collects information on incidence, prevalence and survival from specific geographic areas representing 28% of the U.S. population. The SEER-Medicare database links the SEER data with Medicare records for the U.S. population of age 65 years or older. Contains demographical (age, gender, race/ethnicity, marital status, census data), comorbidities, and tumor characteristics (date of diagnosis, stage, hormone receptor status ) Potosky AL, et al, Med Care. 1993

19 Proprietary datasets that meet HIPPA requirements for confidentiality, and undergo quality validity checks. Files released when 100% of claims have been paid. Commercial Claims & Encounters dataset: large, nationwide, employment-based database that contains information on medical claims and outpatient prescription claims for employees and dependents. Includes a younger population, comprehensive geographic area, contains demographical and comorbid data from nationwide private medical insurance claims. It does not contain tumor characteristics.

20 Inclusion / Exclusion Criteria SEER-Medicare and CERCIT Inclusion: 1 st DX of breast cancer, age 66 years, stage I III, DX between 2003 and 2007, had lumpectomy or mastectomy; full coverage Medicare Part A and B during 12 months before and after DX, not an HMO member. Exclusion: previous DX of any cancer type, stage IV patients

21 Inclusion / Exclusion Criteria MarketScan Inclusion: incident breast cancer DX between 2003 and 2007, aged <65 yrs, who had a lumpectomy or mastectomy, with continuous coverage during 3 months before and 12 months after DX. Exclusion: previous cancer of any type.

22 Identification of Claims Chemotherapy claims by specific HCPCS J codes (anthracyclines: J9000, J9001, J9010, J9178; taxanes: J9170, J9264, J9265) Mastectomy: ICD-9 codes to 85.48; CPT Codes 19180, 19182, 19200, 19220, 19240, to Lumpectomy: ICD-9 codes to CPT codes 19110, 19120, 19125, 19126, 19160, 19162, 19301, 19302

23 Groups for Comparison (HER2 neg) 1) Anthracycline (A) : A, +/- 5-FU, +/- cyclophosphamide (C); no taxanes, no trastuzumab, no other chemo 2) Taxane (T): docetaxel + C, only 3) A + T : anthracycline, +/- 5-FU, +/- C, taxanes (T or paclitaxel), no other chemo

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28 Hospitalization Number of hospitalization admissions between first chemotherapy claim and 30 days, 6 months and 1 year after Accumulated numbers of days that patients remained hospitalized

29 MarketScan

30 SEER - Medicare

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32 Hospitalization due to Toxicities Reason for hospitalization: infection, neutropenia, fever, thrombocytopenia, dehydration, anemia, delirium, adverse effects of systemic therapy Du et al. JCO 2002

33 MarketScan Specific

34 Discussion Points A + T was the most common chemotherapy regimen used in all groups Non-A (T) regimen use increased after 2005 Majority of patients were not hospitalized At 30 days the hospitalization rates were not very different among the groups At 6 and 12 months, the hospitalization rates were higher with A + T, although the length of stay was higher with T in some subgroups Toxicity specific hospitalization was not very different in the MarketScan group

35 Limitations Lack of Stage in the MarketScan database Chemotherapy-induced toxicities may be underrepresented by hospitalization data Medicare billing and errors capturing claims can occur.

36 Next Compare differences in medical costs in the initial treatment phase between anthracycline-based and taxane-based chemotherapy regimens. Identify variables associated with short-term toxicities in each type of chemotherapy regimen (anthracyclinebased and taxane-based).

37 Acknowledgements Dr. Sharon H Giordano Ning Zhang Jiangong Niu Yufeng Zhang