Sibylle Loibl1,2, Frederik Marmé3, Miguel Martin4,5, Michael Untch6, Hervé Bonnefoi7, Sung-Bae Kim8, Harry Bear9,10, Nicole McCarthy11, Mireia Melé Olivé5,12, Karen Gelmon13, José García-Sáenz5,14, Catherine M Kelly15, Toralf Reimer16, Masakazu Toi17, Hope S Rugo18, Carsten Denkert1,19, Michael Gnant20,21, Andreas Makris22, Maria Koehler23, Cynthia Huang-Bartelett23, Maria Jose Lechuga Frean23, Marco Colleoni24, Gustavo Werutsky25, Sabine Seiler1, Nicole Burchardi1, Valentina Nekljudova1, Gunter von Minckwitz1. 1. German Breast Group, Neu-Isenburg, Germany. 2. Center for Hematology and Oncology Bethanien, Frankfurt, Germany. 3. Department of Gynaecology and Obstetrics, University Hospital Mannheim, Mannheim, Germany. 4. Instituto de Investigacion Sanitaria Gregorio Marañon, CIBERONC, Universidad Complutense, Madrid, Spain. 5. GEICAM, Madrid, Spain. 6. Department of Gynaecology and Obstetrics, Breast Cancer Center, HELIOS Klinikum Berlin Buch, Berlin, Germany. 7. UCBG (Unicancer Breast Cancer Group) and Institut Bergonié, Université de Bordeaux, Bordeaux, France. 8. Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, and KCSG (Korean Cancer Study Group), Korea. 9. Division of Surgical Oncology, Massey Cancer Center, Virginia Commonwealth University, VCU Health, Richmond, VA. 10. NSABP Foundation, Pittsburgh, PA. 11. Breast Cancer Trials Australia and New Zealand, Newcastle, Australia. 12. Oncology Research Group, Hospital Universitario Sant Joan de Reus, Reus, Spain. 13. BC Cancer Agency, Vancouver, British Columbia, Canada. 14. Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), Madrid, Spain. 15. Mater Misericordiae University Hospital and Breast Group, Cancer Trials, Dublin, Ireland. 16. Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany. 17. Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 18. Breast Department, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. 19. Institute of Pathology, University Hospital Marburg and Philipps-Universität Marburg, Germany. 20. Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 21. ABCSG, Vienna, Austria. 22. Mount Vernon Cancer Centre, Northwood, United Kingdom. 23. Pfizer Inc, New York, NY. 24. IEO, European Institute of Oncology, IRCCS, Milan, Italy. 25. Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil.
Abstract
PURPOSE: About one third of patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) will relapse. Thus, additional therapy is needed. Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor demonstrating efficacy in the metastatic setting. PATIENTS AND METHODS: PENELOPE-B (NCT01864746) is a double-blind, placebo-controlled, phase III study in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer without a pathological complete response after taxane-containing NACT and at high risk of relapse (clinical pathological staging-estrogen receptor grading score ≥ 3 or 2 and ypN+). Patients were randomly assigned (1:1) to receive 13 cycles of palbociclib 125 mg once daily or placebo on days 1-21 in a 28-day cycle in addition to endocrine therapy (ET). Primary end point is invasive disease-free survival (iDFS). Final analysis was planned after 290 iDFS events with a two-sided efficacy boundary P < .0463 because of two interim analyses. RESULTS:One thousand two hundred fifty patients were randomly assigned. The median age was 49.0 years (range, 19-79), and the majority were ypN+ with Ki-67 ≤ 15%; 59.4% of patients had a clinical pathological staging-estrogen receptor grading score ≥ 3. 50.1% received aromatase inhibitor, and 33% of premenopausal women received a luteinizing hormone releasing hormone analog in addition to either tamoxifen or an aromatase inhibitor. After a median follow-up of 42.8 months (92% complete), 308 events were confirmed. Palbociclib did not improve iDFS versus placebo added to ET-stratified hazard ratio, 0.93 (95% repeated CI, 0.74 to 1.17) and two-sided weighted log-rank test (Cui, Hung, and Wang) P = .525. There was no difference among the subgroups. Most common related serious adverse events were infections and vascular disorders in 113 (9.1%) patients with no difference between the treatment arms. Eight fatal serious adverse events (two palbociclib and six placebo) were reported. CONCLUSION: Palbociclib for 1 year in addition to ET did not improve iDFS in women with residual invasive disease after NACT.
RCT Entities:
PURPOSE: About one third of patients with hormone receptor-positive, humanepidermal growth factor receptor 2-negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) will relapse. Thus, additional therapy is needed. Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor demonstrating efficacy in the metastatic setting. PATIENTS AND METHODS: PENELOPE-B (NCT01864746) is a double-blind, placebo-controlled, phase III study in women with hormone receptor-positive, humanepidermal growth factor receptor 2-negative primary breast cancer without a pathological complete response after taxane-containing NACT and at high risk of relapse (clinical pathological staging-estrogen receptor grading score ≥ 3 or 2 and ypN+). Patients were randomly assigned (1:1) to receive 13 cycles of palbociclib 125 mg once daily or placebo on days 1-21 in a 28-day cycle in addition to endocrine therapy (ET). Primary end point is invasive disease-free survival (iDFS). Final analysis was planned after 290 iDFS events with a two-sided efficacy boundary P < .0463 because of two interim analyses. RESULTS: One thousand two hundred fifty patients were randomly assigned. The median age was 49.0 years (range, 19-79), and the majority were ypN+ with Ki-67 ≤ 15%; 59.4% of patients had a clinical pathological staging-estrogen receptor grading score ≥ 3. 50.1% received aromatase inhibitor, and 33% of premenopausal women received a luteinizing hormone releasing hormone analog in addition to either tamoxifen or an aromatase inhibitor. After a median follow-up of 42.8 months (92% complete), 308 events were confirmed. Palbociclib did not improve iDFS versus placebo added to ET-stratified hazard ratio, 0.93 (95% repeated CI, 0.74 to 1.17) and two-sided weighted log-rank test (Cui, Hung, and Wang) P = .525. There was no difference among the subgroups. Most common related serious adverse events were infections and vascular disorders in 113 (9.1%) patients with no difference between the treatment arms. Eight fatal serious adverse events (two palbociclib and six placebo) were reported. CONCLUSION:Palbociclib for 1 year in addition to ET did not improve iDFS in women with residual invasive disease after NACT.
Authors: Stefania Morganti; Antonio Marra; Edoardo Crimini; Paolo D'Amico; Paola Zagami; Giuseppe Curigliano Journal: Breast Cancer Res Treat Date: 2022-02-06 Impact factor: 4.872
Authors: Ilana Schlam; Paolo Tarantino; Stefania Morganti; Filipa Lynce; Dario Trapani; Erica L Mayer; Ana C Garrido-Castro; Ada Waks; Sara M Tolaney Journal: Drugs Date: 2022-10-07 Impact factor: 11.431
Authors: Nina Ditsch; Achim Wöcke; Michael Untch; Christian Jackisch; Ute-Susann Albert; Maggie Banys-Paluchowski; Ingo Bauerfeind; Jens-Uwe Blohmer; Wilfried Budach; Peter Dall; Eva Maria Fallenberg; Peter A Fasching; Tanja N Fehm; Michael Friedrich; Bernd Gerber; Oleg Gluz; Nadia Harbeck; Jörg Heil; Jens Huober; Hans H Kreipe; David Krug; Thorsten Kühn; Sherko Kümmel; Cornelia Kolberg-Liedtke; Sibylle Loibl; Diana Lüftner; Michael Patrick Lux; Nicolai Maass; Christoph Mundhenke; Ulrike Nitz; Tjoung-Won Park-Simon; Toralf Reimer; Kerstin Rhiem; Achim Rody; Marcus Schmidt; Andreas Schneeweiss; Florian Schütz; Hans-Peter Sinn; Christine Solbach; Erich-Franz Solomayer; Elmar Stickeler; Christoph Thomssen; Isabell Witzel; Volkmar Müller; Wolfgang Janni; Marc Thill Journal: Breast Care (Basel) Date: 2022-05-05 Impact factor: 2.268
Authors: Adam Ofri; Danika Zuidersma; Connie I Diakos; Amanda Stevanovic; Matthew Wong; Samriti Sood; Jaswinder S Samra; Anthony J Gill; Anubhav Mittal Journal: Front Surg Date: 2022-06-24
Authors: Stephen F Madden; Mattia Cremona; Angela M Farrelly; Weng Hei Low; Jean McBryan Journal: Cancer Gene Ther Date: 2022-10-20 Impact factor: 5.854
Authors: Lynn Symonds; Isaac Jenkins; Hannah M Linden; Brenda Kurland; Julie R Gralow; Vijayakrishna V K Gadi; Georgiana K Ellis; Qian Wu; Eve Rodler; Pavani Chalasani; Xiaoyu Chai; Jinny Riedel; Alison Stopeck; Ursa Brown-Glaberman; Jennifer M Specht Journal: Clin Breast Cancer Date: 2021-05-24 Impact factor: 3.225
Authors: Dominik Dannehl; Lea L Volmer; Martin Weiss; Sabine Matovina; Eva-Maria Grischke; Ernst Oberlechner; Anna Seller; Christina B Walter; Markus Hahn; Tobias Engler; Sara Y Brucker; Andreas D Hartkopf Journal: J Pers Med Date: 2022-03-02