Adjuvant Systemic Therapy in Women with Early Breast
Adjuvant Systemic Therapy in Women with Early Breast Cancer and Intermediate Prosigna ROR Scores: Is Chemotherapy Use Declining? Evidence From a Large Practice Lowell L. Hart, MD, FACP Scientific Director of Research, Florida Cancer Specialists, Fort Myers, FL Associate Professor of Medicine, Hematology and Oncology Wake Forest University School of Medicine, Winston-Salem, NC
Who We Are • • Founded in 1984 Largest privately-held oncology/hematology practice 99 offices, 85 clinical sites 230+ physicians 220+ nurse practitioners and physician assistants 3, 500+ employees Ancillaries: – – – 2 Care management Clinical research Central laboratory Oral oncolytic pharmacy Radiology
Integrated Technology Platform Fully integrated including: EMR, Lab, Practice Management, PACS and Inventory Management Fully web based – ‘available anywhere / anytime’ All solutions centrally managed in secure data center with secondary disaster recovery location
Hematopathology & Anatomical Pathology Services • TC and PC flow cytometry • Flow cytometry can be done for bone marrow, peripheral blood, soft tissue and PNH testing • Hem FISH • Tissue FISH • Cytogenetics • Prosigna/PAM 50 • Histology - immunohistochemical (IHC) stains, special stains and Cytology processing • Interpretation of hgb electrophoresis • Interpretation of serum protein electrophoresis and serum immunofixation • Anatomical Pathology Services • Interpretation of molecular tests
Prosigna® in Clinical Routine for e. BC patients at Florida Cancer Specialists Post-menopausal HR+/HER 2 - N 0/N+1 -3 patients samples tested 2016 Florida Cancer Specialists Made Decision to Bring Tests Inhouse 2019 Nearly 2000 Patients Have Received the Prosigna at FL Cancer Specialists
The estimated frequency of chemotherapy using SEER-Medicare data showed that a minority of women received chemotherapy in the pretrial scenario.
What answers are provided from current prospective evidence and what additional question are raised? MINDACT Cardoso F, et al. N Engl J Med 2016; 375: 717 -729. TAILORx Sparano et al. N Engl J Med 2018 Jul 12; 379(2): 111 -121 Sparano et al. N Engl J Med 2019 Jun 20; 380(25): 2395 -2405 Sparano et al. N Engl J Med 2015 Nov 19; 373(21): 2005 -14
Summary of Challenges in Interpretation of TAILORx • Overall population is primarily low risk (<10% risk of DR) as low event rate indicates • Treatment crossover impacts accuracy of measured benefit of CT • Lack of OFS data and late separation of KM curves raises question of appropriate therapy for premenopausal patients • Clinical-pathologic factors not considered by Oncotype DX influence benefit of CT • Impact of TAILORx on physician practice has been generally overstated • Perspective of international guidelines is not refuted by TAILORx • • • Less than 10% risk of DR = No Benefit Greater than 10% risk of DR = Significant Benefit Prior to TAILORx, SEER database indicates low usage of CT in postmenopausal RS 11 -25 Dowsett M & Turner N J Clin Oncol. 2019 Mar 20; 37(9): 689 -692 Rossi PG et al. , JNCI J Natl Cancer Inst (2020) 112(3). Sparano JA et al. N Engl J Med. 2018 Jul 12; 379(2): 111 -121. Sparano JA, Gray R. J Clin Oncol. 2019 Jul 20; 37(21): 1841 -1842
Oncotype. DX TAILORx Study Probability of Distant Recurrence by Age and Clinical Risk ARM A ARM B ARM C ARM D RS < 11 Endocrine Therapy Alone RS 11 - 25 Chemotherapy Plus Endocrine Therapy RS > 25 Chemotherapy Plus Endocrine Therapy Low Clin Risk 2. 6% ± 0. 8 3. 5% ± 0. 6 4. 0% ± 0. 7 7. 0% ± 2. 4 High Clin Risk 7. 4% ± 3. 4 9. 3% ± 1. 9 8. 3% ± 1. 5 19. 8% ± 3. 9 Low Clin Risk 1. 8% ± 0. 9 4. 7% ± 1. 0 3. 9% ± 1. 0 6. 2% ± 2. 5 High Clin Risk 0% (n = 64) 12. 3% ± 2. 4 6. 1% ± 1. 8 15. 2% ± 3. 3 • > 50 yr • ≤ 50 yr Sparano et al. N Engl J Med 2019 Jun 20; 380(25): 2395 -2405
Oncotype. DX TAILORx Study Probability of Distant Recurrence by Age and Clinical Risk ARM A ARM B ARM C ARM D RS < 11 Endocrine Therapy Alone RS 11 - 25 Chemotherapy Plus Endocrine Therapy RS > 25 Chemotherapy Plus Endocrine Therapy Low Clin Risk 2. 6% ± 0. 8 3. 5% ± 0. 6 High Clin Risk 7. 4% ± 3. 4 9. 3% ± 1. 9 Low Clin Risk 1. 8% ± 0. 9 4. 7% ± 1. 0 High Clin Risk 0% (n = 64) 12. 3% ± 2. 4 • > 50 yr - 0. 5% 4. 0% ± 0. 7 7. 0% ± 2. 4 8. 3% ± 1. 5 19. 8% ± 3. 9 0. 8% 3. 9% ± 1. 0 6. 2% ± 2. 5 6. 2% 6. 1% ± 1. 8 15. 2% ± 3. 3 1. 6% • ≤ 50 yr Sparano et al. N Engl J Med 2019 Jun 20; 380(25): 2395 -2405
Prosigna ROR Score Algorithm
FCS Observational Study Design • Separated 2 groups of Intermediate Risk Patient as identified using the Prosigna assay • Data review determined if patients received hormonal adjuvant therapy alone or chemotherapy plus hormonal therapy • Only node-negative patients used for current analysis, similar to TAILORx group Hypothesized that the use of chemo-hormonal adjuvant therapy for intermediate risk patients would be declining in this real-world setting after the first presentation of TAILORx results in June 2018
Decrease of Chemotherapy in Prosigna assigned Intermediate risk patients Time Period Dates Pre-TAILORx September 1, 2017 May 31, 2018 Post. TAILORx June 1, 2018 - March 31, 2019 Intermediate Tests Intermediate Total Prosigna Results Receiving Test Results Tests - N Chemotherapy - N N (%) 312 453 61 (19. 6%) 15 (24. 5%) 105 (23. 2%) 17 (16. 2%) Percentage Reduction in Chemotherapy Use in Intermediate Risk Patients 33. 9%
Conclusion: Moving towards routine practice personalized medicine for EBC HR+/HER 2 - • A large private practice significantly decreased the use of adjuvant chemotherapy in Prosigna-intermediate-risk patients post-TAILORx • Physicians comfortable extrapolating evidence from randomized trials where there is strong retrospective evidence for Prosigna® 2 nd gen assays • Although economic analysis not performed, decline in the number of chemotherapy patients suggests savings for medical system, along with patient benefit • EMR database to be analysed for physician behavior with respect to duration of endocrine therapy as well as new adjuvant therapies in HR+/HER 2 - e. BC patients
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