Postmastectomy Radiation Therapy: An ASTRO-ASCO-SSO Clinical Practice Guideline
Guidelines for post-mastectomy radiation include patients who received neoadjuvant therapy, with or without residual disease after treatment. A good topic to review.
Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer
Author(s): Mario Campone, M.D., Ph.D.1; Michelino De Laurentiis, M.D., Ph.D.2; Komal Jhaveri, M.D.3,4; Xichun Hu, M.D., Ph.D.5; Sylvain Ladoire, M.D., Ph.D.6; Anne Patsouris, M.D., Ph.D.7; Claudio Zamagni, M.D.8; Jiuwei Cui, M.D., Ph.D.9; Marina Cazzaniga, M.D.10; Timucin Cil, M.D.11; Katarzyna J. Jerzak, M.D.12; Christian Fuentes, M.D.13; Tetsuhiro Yoshinami, M.D., Ph.D.14; Alvaro Rodriguez-Lescure, M.D., Ph.D.15; Ahmet Sezer, M.D. https://orcid.org/0000-0002-6445-143916; Andrea Fontana, M.D., Ph.D.17; Valentina Guarneri, M.D., Ph.D.18,19; Andrea Molckovsky, M.D.20; Marie-Ange Mouret-Reynier, M.D.21; Umut Demirci, M.D., Ph.D.22; Yongqiang Zhang, M.D.23; Olga Valota, M.S.24; Dongrui R Lu, M.S.25; Marcella Martignoni, Ph.D.24; Janaki Parameswaran, M.D.26; Xin Zhi, Ph.D.26; Erika P. Hamilton, M.D.27; the VERITAC-2 Study Group*28;
Source: N Engl J Med 2025;393:556-568
Dr. Maen Hussein's Thoughts
Vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) estrogen receptor (ER) degrader that directly utilizes the ubiquitin–proteasome system. It was compared to fulvestrant in patients who had received one prior line of hormonal therapy with a CDK4/6 inhibitor. Among patients with ESR1 mutations, Vepdegestrant demonstrated a median progression-free survival (PFS) of 5.0 months versus 2.1 months with fulvestrant. In the overall population, the median PFS was 3.8 months for Vepdegestrant and 3.6 months for fulvestrant, indicating that the drug showed particular efficacy in tumors harboring ESR1 mutations.
BACKGROUND
Vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) estrogen receptor (ER) degrader that directly harnesses the ubiquitin–proteasome system.
METHODS
In this phase 3, open-label, randomized trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer who had received one previous line of cyclin-dependent kinase 4 and 6 inhibitor therapy plus one line of endocrine therapy (and up to one additional line of endocrine therapy). Patients were randomly assigned in a 1:1 ratio to receive vepdegestrant at a dose of 200 mg orally once every day of each 28-day cycle or fulvestrant at a dose of 500 mg, administered intramuscularly, on day 1 and day 15 of cycle 1 and on day 1 of subsequent cycles, with randomization stratified according to ESR1-mutation status and presence or absence of visceral disease. The primary end point was progression-free survival as assessed by blinded independent central review among the patients with ESR1 mutations and among all the patients who underwent randomization. Progression-free survival was estimated with Kaplan–Meier methods and hazard ratios with a stratified Cox proportional-hazards model. Research Summary Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Breast Cancer
RESULTS
A total of 624 patients underwent randomization; 313 were assigned to receive vepdegestrant, and 311 to receive fulvestrant. Among the 270 patients with ESR1 mutations, the median progression-free survival was 5.0 months (95% confidence interval [CI], 3.7 to 7.4) with vepdegestrant and 2.1 months (95% CI, 1.9 to 3.5) with fulvestrant (hazard ratio, 0.58 [95% CI, 0.43 to 0.78]; P
CONCLUSIONS
Among patients with ER-positive, HER2-negative advanced breast cancer, vepdegestrant was associated with significantly longer progression-free survival than fulvestrant in the subgroup with ESR1 mutations but not in the full patient population. (Funded by Pfizer and Arvinas Estrogen Receptor; VERITAC-2 ClinicalTrials.gov number, NCT05654623.)
Author Affiliations
1Institut de Cancérologie de l’Ouest Angers-Nantes, Saint-Herblain, France; 2Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale,” Naples, Italy; 3Memorial Sloan Kettering Cancer Center, New York; 4Weill Cornell Medical College, New York; 5Shanghai Cancer Center, Fudan University, Shanghai, China; 6Centre Georges Francois Leclerc, Dijon, France; 7Institut de Cancérologie de l’Ouest Angers-Nantes, Angers, France; 8IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy; 9First Hospital of Jilin University, Changchun, China; 10Phase 1 Research Unit, Fondazione IRCCS San Gerardo, Monza, Italy; 11Health and Science University, Adana City Hospital, Adana, Turkey; 12Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto; 13Fundación Respirar, Buenos Aires; 14Graduate School of Medicine, Osaka University, Osaka, Japan; 15Hospital General Universitario de Elche, Elche, Spain; 16Baskent University Adana Application and Research Center, Adana, Turkey; 17Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; 18Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Padua, Italy; 19University of Padova, Padua, Italy; 20Grand River Regional Cancer Centre, Kitchener, ON, Canada; 21Centre Jean Perrin, Clermont-Ferrand, France; 22Memorial Ankara Hospital, Ankara, Turkey; 23Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing; 24Pfizer, Milan; 25Pfizer, San Diego, CA; 26Arvinas Operations, New Haven, CT; 27Breast Cancer Research Program, Sarah Cannon Research Institute, NashvilleRelated Articles
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