Abstract GS3-08: Pathological complete response predicts event-free and distant disease-free survival in the I-SPY2 TRIAL
| Autor: | Anthony M. Magliocco, AM DeMichele, Rashmi Krishna Murthy, Kirsten K. Edmiston, J Ritter, LJ Esserman, J Wisell, Y-Y Chen, Jane Perlmutter, Gillian L. Hirst, Erin D. Ellis, Andres Forero-Torres, G Keeney, Kathleen Kemmer, A Tipps, Jay Zeck, AS Clark, F Fan, Husain Sattar, Khalid Amin, G Krings, Ossama Tawfik, Megan L. Troxell, Susan Minton, Sunati Sahoo, Hongzheng Zhang, Stamatakos, A Adams, S Asare, AD Elias, Fraser Symmans, Mara H. Rendi, B Kallakury, Barbara Haley, Molly Klein, T Ocal, A Zelnak, L.J. van 't Veer, Michael Feldman, Sharon Sams, B Datnow, Tuyethoa Vinh, Kathy S. Albain, M Melisko, Je Lang, AJ Chien, K Gwin, Y Fang, Shuko Harada, NM Hylton, X Duan, F Hasteh, Jeffery Mueller, S Thornton, R Tickman, Shi Wei, Qamar J. Khan, N Klipfel, Larissa A. Korde, Judy C. Boughey, Awais Mansoor, Gabrielle M. Baker, Ruby Singhrao, C Ersahin, R Gamez, Donald A. Berry, D Yee, Rita Nanda, Claudine Isaacs, Donald W. Northfelt, Hyo S. Han, Rebecca K. Viscusi, Anne M. Wallace, Christina Yau, L Grasso LeBeau, R Balassanian, Beiyun Chen, N Weidner, HS Rugo |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Patritumab Veliparib Population Confirmatory trial 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Trastuzumab Internal medicine medicine Clinical endpoint education education.field_of_study business.industry Surrogate endpoint 030104 developmental biology chemistry 030220 oncology & carcinogenesis Pertuzumab business medicine.drug |
| Zdroj: | Cancer Research. 78:GS3-08 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.sabcs17-gs3-08 |
| Popis: | Background: Pathological complete response (pCR) is accepted by FDA as a surrogate endpoint for accelerated approval of targeted agents in combination with chemotherapy based on better long-term outcomes compared to residual disease (Cortazar 2014). Methods: The multi-center, adaptively-randomized I-SPY2 platform trial uses pCR as the primary endpoint to identify investigational agents that will improve outcomes in women with stage 2/3 breast cancer with high risk of early recurrence, across all signatures, based on hormone receptor (HR), HER2, and 70-gene (MammaPrint) status. For patients with HR+ HER2- tumors, only 70-gene (Mammaprint) high-risk patients are enrolled. To date, 1200+ patients have been randomized to one of 14 arms: control (paclitaxel followed by AC); veliparib/carboplatin; neratinib; MK2206; trebananib; trastuzumab/pertuzumab; ado-trastuzumab emtansine/pertuzumab; pembrolizumabx4; ganitumab/metformin; ganetespib; PLX-3397. 7 agents graduated in at least one signature (> 85% probability of success in a 300-patient phase III confirmatory trial); 2 did not graduate; 1 stopped for toxicity, and 3 are enrolling (patritumab/trastuzumab, talazoparib/irinotecan, pembrolizumabx8). Local pathologists were centrally trained using the Residual Cancer Burden (RCB) assessment to ensure uniform evaluation and response classification; RCB 0 = pCR. Results: We evaluated the relationship between pCR and event free (EFS) and distant disease free survival (DDFS) in the first 522 pts (median follow-up:2.5 years). 180 pts achieved pCR (36%) while 338 did not (RCB=1-3). There were 82 EFS and 65 DRFS events. Over the entire group (including all arms), pCR was highly associated with 3-year EFS (p 3-year survival (pCR group)Hazard Ratio OverallOverallHR+/HER2-HER2+TNBCEFS97%0.08 (0.03-0.23)0.14 (0.02-1.04)0 (NA)0.11 (0.03-0.37)DDFS98%0.08 (0.03-0.26)0.17 (0.01-1.23)0 (NA)0.09 (0.02-0.40) Conclusions: The first long-term efficacy results from the I-SPY2 TRIAL demonstrate that achieving pCR is a very strong surrogate endpoint for improved EFS and DDFS in a high-risk population, across all treatment arms, regardless of subtype. I-SPY2 shows substantially lower estimated EFS hazards for patients achieving pCR, compared to the 5 yr EFS hazard ratio for pCR vs not in Cortazar (hazard ratio 0.49), demonstrating important differences between a metaanalysis compared to a platform trial with uniform high-risk eligibility, standardized pathology assessment, and multiple targeted therapies. Our data support the use of pCR as a primary endpoint for accelerated approval of new drugs if EFS is evaluated in the same population. Based on these findings, the I-SPY2 TRIAL will test whether therapy can be deescalated or escalated for individual patients with the goal of achieving pCR for all. Citation Format: Yee D, DeMichele A, Isaacs C, Symmans F, Yau C, Albain KS, Hylton NM, Forero-Torres A, van't Veer LJ, Perlmutter J, Rugo HS, Melisko M, Chen Y-Y, Balassanian R, Krings G, Datnow B, Hasteh F, Tipps A, Weidner N, Zhang H, Tickman R, Thornton S, Ritter J, Amin K, Klein M, Chen B, Keeney G, Ocal T, Feldman M, Klipfel N, Sattar H, Mueller J, Gwin K, Baker G, Kallakury B, Zeck J, Duan X, Ersahin C, Gamez R, Troxell M, Mansoor A, Grasso LeBeau L, Sams S, Wisell J, Wei S, Harada S, Vinh T, Stamatakos MD, Tawfik O, Fan F, Adams A, Rendi M, Minton S, Magliocco A, Sahoo S, Fang Y, Hirst G, Singhrao R, Asare SM, Wallace AM, Chien AJ, Ellis ED, Han HS, Clark AS, Boughey JC, Elias AD, Nanda R, Korde L, Murthy R, Lang J, Northfelt D, Khan Q, Edmiston KK, Viscusi R, Haley B, Kemmer K, Zelnak A, Berry DA, Esserman LJ. Pathological complete response predicts event-free and distant disease-free survival in the I-SPY2 TRIAL [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS3-08. |
| Databáze: | OpenAIRE |
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