Toxicities of Chemotherapy Regimens used in Early Breast ...Breast Cancer! Early Breast Cancer...
Transcript of Toxicities of Chemotherapy Regimens used in Early Breast ...Breast Cancer! Early Breast Cancer...
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
1. Background
2. Data Sources
3. Methods
4. Results
5. Discussion
Outline
Siegel et al, CA Cancer J Clin 2012
• 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
Background Treatment of Breast Cancer
Chemotherapy Benefits in Breast Cancer
Early Breast Cancer Trialists Group (EBCTG), Lancet 2005
• Chemotherapy reduces breast cancer (BC) recurrence and mortality • Shown in randomized control trials and meta-analysis. • 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 50–69 years.
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
• 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 anthracycline-based regimen is considered standard.
Anthracycline-based Regimen vs. CMF
Clarke M, Ann Oncology. 2006 Jones SE, et al, JCO. 2006
• 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%
Shift in Pattern of Care • 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 2008.
• 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.
Giordano SH, Lin Y, Kuo Y, et al: Anthracyline use among women with breast cancer. ASCO Meeting Abstracts 29:Abstract 1019, 2011
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.
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 non-anthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia.
• Estimated Enrollment: 2000 • Study Start Date: May 2007 • Estimated Study Completion Date: May 2015
Phase III Clinical Trial TAC vs. TC
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)
Objective
• To compare differences in toxicities between anthracycline-based and taxane-based breast cancer chemotherapy regimens, using hospitalization information from population-based databases.
• 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 )
Data Sources SEER-‐Medicare database
Potosky AL, et al, Med Care. 1993
• 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.
Inclusion / Exclusion Criteria SEER-Medicare and CERCIT
• Inclusion: 1st 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
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.
Identification of Claims
• Chemotherapy claims by specific ‘HCPCS J’ codes (anthracyclines: J9000, J9001, J9010, J9178; taxanes: J9170, J9264, J9265)
• Mastectomy: ICD-9 codes 85.41 to 85.48; CPT Codes 19180, 19182, 19200, 19220, 19240, 19303 to 19307
• Lumpectomy: ICD-9 codes 85.20 to 85.25 CPT codes 19110, 19120, 19125, 19126, 19160, 19162, 19301, 19302
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
Groups
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
MarketScan
SEER - Medicare
CERCIT
Hospitalization due to Toxicities
• Reason for hospitalization: infection, neutropenia, fever, thrombocytopenia, dehydration, anemia, delirium, adverse effects of systemic therapy Du et al. JCO 2002
MarketScan Specific
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
• Lack of Stage in the MarketScan database
• Chemotherapy-induced toxicities may be underrepresented by hospitalization data
• Medicare billing and errors capturing claims can occur.
Limitations
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 (anthracycline-based and taxane-based).
Acknowledgements
• Dr. Sharon H Giordano • Ning Zhang • Jiangong Niu • Yufeng Zhang