Messaggi chiave
- SERENA-2 è 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 è 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).
- 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-.
Abstract
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.
Methods
- 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).
- 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.
Findings
- 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.
- 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.
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.