Camizestrant vs Fulvestrant in Post-Menopausal Women: SERENA-2 Trial Results

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Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): a multi-dose, open-label, randomised, phase 2 trial Oliveira M, Pominchuk D, Nowecki Z, et al. Lancet Oncol 2024;25(11):1424-1439 Background & methods Results Conclusions Messaggi chiave Powered by

MESSAGGI CHIAVE | 1 SERENA-2 uno studio multicentrico di fase II, randomizzato, in aperto, di confronto tra camizestrant (75, 150 o 300 mg una volta al giorno per via orale) rispetto a fulvestrant (500 mg una volta al mese per via intramuscolare) in pazienti affette da carcinoma mammario (BC) avanzato ER+/HER2- con recidiva o progressione della malattia dopo almeno una linea di terapia endocrina. Nel periodo maggio 2020 - agosto 2021, 240 pazienti sono state randomizzate a ricevere camizestrant (75 mg [n = 74], 150 mg [n = 73], 300 mg [n = 20]) o fulvestrant (n = 73). Dopo un follow-up mediano di 16,6, 16,3 e 14,7 mesi per i gruppi camizestrant 75 mg, camizestrant 150 mg e fulvestrant, la sopravvivenza libera da progressione mediana stata di 7,2, 7,7 e 3,7 mesi, rispettivamente, con un hazard ratio per camizestrant 75 mg vs fulvestrant e camizestrant 150 mg vs fulvestrant rispettivamente pari a 0,59 (IC 90%, 0,42-0,82; p = 0,017) e 0,64 (IC 90%, 0,46-0,89; p = 0,0090). Powered by

MESSAGGI CHIAVE | 2 Eventi avversi (EA) correlati al trattamento sono stati osservati nel 53, 67, 70 e 18% delle pazienti nei gruppi camizestrant 75 mg, camizestrant 150 mg, camizestrant 300 mg e fulvestrant, con una frequenza di EA emergenti dal trattamento (TEAE) di grado 3 non superiore al 3%, a prescindere dal braccio, e un incidenza di TEAE seri pari all 8, 10, 10 e 5% nei quattro gruppi dello studio, rispettivamente. Non sono stati registrati decessi dovuti alla terapia. Nel complesso, i risultati dello studio supportano l ulteriore sviluppo di camizestrant per il trattamento del BC ER+/HER2-. Powered by

BACKGROUND Resistance to endocrine therapies in hormone receptor- positive breast cancer is challenging. We aimed to assess the next-generation oral selective oestrogen receptor degrader (SERD) and complete oestrogen receptor antagonist, camizestrant, versus the first-approved SERD, fulvestrant, in post-menopausal women with oestrogen receptor-positive, HER2-negative, advanced breast cancer. Powered by

METHODS | 1 SERENA-2 is an open-label, randomised, phase 2 trial that is being conducted at 74 study centres across Asia, Europe, the Middle East, and North America. Female patients aged 18 years or older who were post-menopausal with histologically or cytologically confirmed metastastic or locoregional oestrogen receptor-positive, HER2-negative breast cancer, an Eastern Cooperative Oncology Group or WHO performance status of 0 or 1, and disease recurrence or progression on at least one line of endocrine therapy, and no more than one previous endocrine therapy in the advanced setting. Patients were initially randomly assigned (1:1:1:1) to receive oral camizestrant once daily at 75 mg, 150 mg, or 300 mg (until the 300 mg group was closed), or fulvestrant intramuscularly at 500 mg (per label). Powered by

METHODS | 2 Randomisation was managed through an interactive web-based system and stratified by previous treatment with CDK4/6 inhibitors and presence of liver and/or lung metastases. The primary objective was to determine clinical efficacy of camizestrant versus fulvestrant at each dose level using the primary endpoint of investigator-assessed progression-free survival, per Response Evaluation Criteria in Solid Tumours (version 1.1), assessed by intention to treat in all randomly assigned patients (full analysis set). No formal statistical comparison for the efficacy analysis of the camizestrant 300 mg dose versus fulvestrant was to be performed. Safety analyses included all randomly assigned patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04214288, and is ongoing. Powered by

FINDINGS | 1 Between May 11, 2020, and Aug 10, 2021, 240 patients were randomly assigned to receive camizestrant 75 mg (n = 74), 150 mg (n = 73), 300 mg (n = 20), or fulvestrant (n = 73), and were included in the full analysis set. All patients received at least one dose of study drug. Median follow-up was 16.6 months (IQR 12.9-19.4) for the camizestrant 75 mg group, 16.3 months (12.9-18.3) for the camizestrant 150 mg group, and 14.7 months (12.7-20.1) for the fulvestrant 500 mg group. Median progression-free survival was 7.2 months (90% CI 3.7-10.9) with camizestrant 75 mg, 7.7 months (5.5-12.9) with camizestrant 150 mg, and 3.7 months (2.0-6.0) with fulvestrant. Powered by

FINDINGS | 2 The hazard ratio for camizestrant 75 mg versus fulvestrant was 0.59 (90% CI 0.42-0.82; p = 0.017), and the hazard ratio for camizestrant 150 mg versus fulvestrant was 0.64 (0.46-0.89; p = 0.0090). Treatment-related adverse events occurred in 39 (53%) of 74 patients in the camizestrant 75 mg group, 49 (67%) of 73 patients in the camizestrant 150 mg group, 14 (70%) of 20 patients in the camizestrant 300 mg group, and 13 (18%) of 73 patients in the fulvestrant group. No single grade 3 or worse treatment-emergent adverse event occurred in more than two (3%) patients in any group. Serious treatment-emergent adverse events occurred in six (8%) patients in the camizestrant 75 mg group, seven (10%) patients in the camizestrant 150 mg group, two (10%) patients in the camizestrant 300 mg group, and four (5%) patients in the fulvestrant group. No treatment-related deaths occurred. Powered by

INTERPRETATION Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further development of camizestrant for the treatment of oestrogen receptor-positive, HER2- negative breast cancer. Powered by

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