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.
First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer
Author(s): François-Clément Bidard, M.D., Ph.D. https://orcid.org/0000-0001-5932-89491; Erica L. Mayer, M.D., M.P.H. https://orcid.org/0000-0001-5430-89572; Yeon Hee Park, M.D., Ph.D.3; Wolfgang Janni, M.D., Ph.D.4; Cynthia Ma, M.D., Ph.D.5; Massimo Cristofanilli, M.D. https://orcid.org/0000-0002-4194-71756; Giampaolo Bianchini, M.D.7; Kevin Kalinsky, M.D.8; Hiroji Iwata, M.D., Ph.D.9; Stephen Chia, M.D.10; Peter A. Fasching, M.D.11; Adam Brufsky, M.D., Ph.D.12; Zbigniew Nowecki, M.D., Ph.D.13; Javier Pascual, M.D. https://orcid.org/0000-0003-3874-278214; Lionel Moreau, M.D.15; Shin-Cheh Chen, M.D.16; Nuri Karadurmus, M.D.17; Einav Nili Gal-Yam, M.D., Ph.D.18; Kyung Hae Jung, M.D., Ph.D.19; Sonia Pernas, M.D., Ph.D.20; Sasha McClain, Pharm.D.21; Wei He, Ph.D.22; Teresa Klinowska, Ph.D.23; Cynthia Huang-Bartlett, M.D.21; Nicholas C. Turner, M.D., Ph.D.24; the SERENA-6 Study Group*26;
Source: DOI: 10.1056/NEJMoa2502929
Dr. Maen Hussein's Thoughts
Our site participated in this study, where patients were tested for ESR1 mutations via circulating tumor DNA (ctDNA). Those who tested positive were switched to camizestrant (Cami), which demonstrated improved progression-free survival.
BACKGROUND
Mutations in ESR1 are the most common mechanism of acquired resistance to treatment with an aromatase inhibitor plus a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor for advanced breast cancer. Camizestrant, a next-generation selective estrogen-receptor (ER) degrader and complete ER antagonist, has shown antitumor activity in ER-positive advanced breast cancer.
METHODS
We tested patients with advanced breast cancer with ER-positive, human epidermal growth factor receptor 2 (HER2)–negative tumors for ESR1 mutations in circulating tumor DNA (ctDNA) once every 2 to 3 months. All the patients had received at least 6 months of first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib). Patients who were found to have an ESR1 mutation and did not have radiologic progression were assigned in a 1:1 ratio to switch to camizestrant (75 mg once daily) with a continued CDK4/6 inhibitor plus placebo in place of an aromatase inhibitor or to continue to receive an aromatase inhibitor plus a CDK4/6 inhibitor plus placebo in place of camizestrant. The primary outcome was investigator-assessed progression-free survival. Research Summary First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer
RESULTS
A total of 3256 patients were tested for an ESR1 mutation. The 315 eligible patients were assigned to switch to camizestrant (157 patients) or to continue to receive an aromatase inhibitor (158 patients). At an interim analysis at a median follow-up of 12.6 months, the median progression-free survival was 16.0 months (95% confidence interval [CI], 12.7 to 18.2) in the camizestrant group and 9.2 months (95% CI, 7.2 to 9.5) in the aromatase-inhibitor group (hazard ratio for progression or death, 0.44; 95% CI, 0.31 to 0.60; P
CONCLUSIONS
In patients with ER-positive, HER2-negative advanced breast cancer with an ESR1 mutation that emerged during treatment, those who were switched to camizestrant with continuation of a CDK4/6 inhibitor during first-line therapy had significantly longer progression-free survival than those who maintained the aromatase-inhibitor combination. (Funded by AstraZeneca; SERENA-6 ClinicalTrials.gov number, NCT04964934.)
Author Affiliations
1Institut Curie, Paris and Saint-Cloud; INSERM Centre d’Investigation Clinique 1428, Paris; Versailles–Saint-Quentin University, Paris–Saclay University, Saint Cloud, France; 2Dana–Farber Cancer Institute, Boston; 3Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 4Universitätsklinikum Ulm, Ulm, Germany; 5Washington University School of Medicine, St. Louis; 6Weill-Cornell Medicine, New York–Presbyterian Hospital, New York; 7IRCCS Ospedale San Raffaele, Milan; 8Winship Cancer Institute, Atlanta; 9Nagoya City University, Nagoya, Japan; 10BC Cancer Agency, Vancouver, Canada; 11Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen–European Metropolitan Region of Nuremberg, University Hospital Erlangen, Erlangen, Germany; 12University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, UPMC Magee-Womens Hospital, Pittsburgh; 13Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie, Warsaw, Poland; 14Hospital Universitario Virgen de la Victoria, Málaga, Spain; 15Pôle Santé République, Clermont-Ferrand, France; 16Chang Gung Medical Foundation Linkou Branch, Taoyuan City, Taiwan; 17Gülhane Training and Research Hospital, University of Health Sciences, Ankara, Turkey; 18Sheba Medical Center, Ramat Gan, Israel; 19Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; 20Institut Català d’Oncologia–Institut d’Investigació Biomèdica de Bellvitge, L’Hospitalet, Barcelona; 21AstraZeneca, Gaithersburg, MD; 22AstraZeneca, Waltham, MA; 23AstraZeneca, Cambridge, United Kingdom; 24Royal Marsden Hospital, LondonRelated Articles
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