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, London

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