Sara M Tolaney1, Hao Guo1, Sonia Pernas1,2, William T Barry1, Deborah A Dillon3, Lauren Ritterhouse3,4, Bryan P Schneider5, Fei Shen5, Kit Fuhrman6, Michele Baltay3, Chau T Dang7,8, Denise A Yardley9, Beverly Moy10, P Kelly Marcom11, Kathy S Albain12, Hope S Rugo13, Mathew J Ellis14, Iuliana Shapira15,16, Antonio C Wolff17, Lisa A Carey18, Beth Overmoyer1, Ann H Partridge1, Clifford A Hudis7,8,19, Ian E Krop1, Harold J Burstein1, Eric P Winer1. 1. 1Dana-Farber Cancer Institute, Boston, MA. 2. 2Institut Català d'Oncologia-H.U.Bellvitge-IDIBELL, Barcelona, Spain. 3. Brigham and Women's Hospital, Boston, MA. 4. 4University of Chicago, Chicago, IL. 5. 5Indiana University School of Medicine, Indianapolis, IN. 6. NanoString Technologies, Seattle, WA. 7. Memorial Sloan Kettering Cancer Center, New York, NY. 8. Weill Medical College of Cornell University, New York, NY. 9. 9Sarah Cannon Cancer Center, Nashville, TN. 10. Massachusetts General Hospital, Boston, MA. 11. Duke Cancer Institute, Durham, NC. 12. Loyola University Chicago Stritch School of Medicine, Maywood, IL. 13. University of California, San Francisco, San Francisco, CA. 14. Baylor Clinic Lester and Sue Smith Breast Center, Houston, TX. 15. Hofstra North Shore-LIJ School of Medicine, New Hyde Park, NY. 16. SUNY Downstate Medical Center, Brooklyn, NY. 17. Johns Hopkins University, Baltimore, MD. 18. University of North Carolina, Chapel Hill, NC. 19. American Society of Clinical Oncology, Alexandria, VA.
Abstract
PURPOSE: The Adjuvant Paclitaxel and Trastuzumab trial was designed to address treatment of patients with small human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The primary analysis of the Adjuvant Paclitaxel and Trastuzumab trial demonstrated a 3-year disease-free survival (DFS) of 98.7%. In this planned secondary analysis, we report longer-term outcomes and exploratory results to characterize the biology of small HER2-positive tumors and genetic factors that may predispose to paclitaxel-induced peripheral neuropathy (TIPN). PATIENTS AND METHODS: In this phase II study, patients with HER2-positive breast cancer with tumors 3 cm or smaller and negative nodes receivedpaclitaxel (80 mg/m2) with trastuzumab for 12 weeks, followed by trastuzumab for 9 months. The primary end point was DFS. Recurrence-free interval (RFI), breast cancer-specific survival, and overall survival (OS) were also analyzed. In an exploratory analysis, intrinsic subtyping by PAM50 (Prosigna) and calculation of the risk of recurrence score were performed on the nCounter analysis system on archival tissue. Genotyping was performed to investigate TIPN. RESULTS: A total of 410 patients were enrolled from October 2007 to September 2010. After a median follow-up of 6.5 years, there were 23 DFS events. The 7-year DFS was 93% (95% CI, 90.4 to 96.2) with four (1.0%) distant recurrences, 7-year OS was 95% (95% CI, 92.4 to 97.7), and 7-year RFI was 97.5% (95% CI, 95.9 to 99.1). PAM50 analyses (n = 278) showed that most tumors were HER2-enriched (66%), followed by luminal B (14%), luminal A (13%), and basal-like (8%). Genotyping (n = 230) identified one single-nucleotide polymorphism, rs3012437, associated with an increased risk of TIPN in patients with grade 2 or greater TIPN (10.4%). CONCLUSION: With longer follow-up, adjuvant paclitaxel and trastuzumab is associated with excellent long-term outcomes. Distribution of PAM50 intrinsic subtypes in small HER2-positive tumors is similar to that previously reported for larger tumors.
RCT Entities:
PURPOSE: The Adjuvant Paclitaxel and Trastuzumab trial was designed to address treatment of patients with small humanepidermal growth factor receptor 2 (HER2)-positive breast cancer. The primary analysis of the Adjuvant Paclitaxel and Trastuzumab trial demonstrated a 3-year disease-free survival (DFS) of 98.7%. In this planned secondary analysis, we report longer-term outcomes and exploratory results to characterize the biology of small HER2-positive tumors and genetic factors that may predispose to paclitaxel-induced peripheral neuropathy (TIPN). PATIENTS AND METHODS: In this phase II study, patients with HER2-positive breast cancer with tumors 3 cm or smaller and negative nodes received paclitaxel (80 mg/m2) with trastuzumab for 12 weeks, followed by trastuzumab for 9 months. The primary end point was DFS. Recurrence-free interval (RFI), breast cancer-specific survival, and overall survival (OS) were also analyzed. In an exploratory analysis, intrinsic subtyping by PAM50 (Prosigna) and calculation of the risk of recurrence score were performed on the nCounter analysis system on archival tissue. Genotyping was performed to investigate TIPN. RESULTS: A total of 410 patients were enrolled from October 2007 to September 2010. After a median follow-up of 6.5 years, there were 23 DFS events. The 7-year DFS was 93% (95% CI, 90.4 to 96.2) with four (1.0%) distant recurrences, 7-year OS was 95% (95% CI, 92.4 to 97.7), and 7-year RFI was 97.5% (95% CI, 95.9 to 99.1). PAM50 analyses (n = 278) showed that most tumors were HER2-enriched (66%), followed by luminal B (14%), luminal A (13%), and basal-like (8%). Genotyping (n = 230) identified one single-nucleotide polymorphism, rs3012437, associated with an increased risk of TIPN in patients with grade 2 or greater TIPN (10.4%). CONCLUSION: With longer follow-up, adjuvant paclitaxel and trastuzumab is associated with excellent long-term outcomes. Distribution of PAM50 intrinsic subtypes in small HER2-positive tumors is similar to that previously reported for larger tumors.
Authors: Francesco Schettini; Tomás Pascual; Benedetta Conte; Nuria Chic; Fara Brasó-Maristany; Patricia Galván; Olga Martínez; Barbara Adamo; Maria Vidal; Montserrat Muñoz; Aranzazu Fernández-Martinez; Carla Rognoni; Gaia Griguolo; Valentina Guarneri; Pier Franco Conte; Mariavittoria Locci; Jan C Brase; Blanca Gonzalez-Farre; Patricia Villagrasa; Sabino De Placido; Rachel Schiff; Jamunarani Veeraraghavan; Mothaffar F Rimawi; C Kent Osborne; Sonia Pernas; Charles M Perou; Lisa A Carey; Aleix Prat Journal: Cancer Treat Rev Date: 2020-01-17 Impact factor: 12.111
Authors: Helena Earl; Louise Hiller; Anne-Laure Vallier; Shrushma Loi; Karen McAdam; Luke Hughes-Davies; Daniel Rea; Donna Howe; Kerry Raynes; Helen B Higgins; Maggie Wilcox; Chris Plummer; Betania Mahler-Araujo; Elena Provenzano; Anita Chhabra; Sophie Gasson; Claire Balmer; Jean E Abraham; Carlos Caldas; Peter Hall; Bethany Shinkins; Christopher McCabe; Claire Hulme; David Miles; Andrew M Wardley; David A Cameron; Janet A Dunn Journal: Health Technol Assess Date: 2020-08 Impact factor: 4.014
Authors: Aleix Prat; Valentina Guarneri; Laia Paré; Gaia Griguolo; Tomás Pascual; Maria V Dieci; Núria Chic; Blanca González-Farré; Antonio Frassoldati; Esther Sanfeliu; Juan M Cejalvo; Montserrat Muñoz; Giancarlo Bisagni; Fara Brasó-Maristany; Loredana Urso; Maria Vidal; Alba A Brandes; Barbara Adamo; Antonino Musolino; Federica Miglietta; Benedetta Conte; Mafalda Oliveira; Cristina Saura; Sònia Pernas; Jesús Alarcón; Antonio Llombart-Cussac; Javier Cortés; Luis Manso; Rafael López; Eva Ciruelos; Francesco Schettini; Patricia Villagrasa; Lisa A Carey; Charles M Perou; Federico Piacentini; Roberto D'Amico; Enrico Tagliafico; Joel S Parker; Pierfranco Conte Journal: Lancet Oncol Date: 2020-11 Impact factor: 41.316