Novel selective estrogen receptor degraders (SERDs) are a promising therapeutic option under investigation for patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. The efficacy of novel SERDs in the treatment of advanced disease has prompted investigation into their use in the early disease setting, to reduce breast cancer recurrence. Here, we describe the design and rationale of the phase III, randomized, open-label CAMBRIA-1 and CAMBRIA-2 studies. CAMBRIA-1 and CAMBRIA-2 are comparing the next-generation oral SERD camizestrant versus standard-of-care endocrine therapy (aromatase inhibitors or tamoxifen) in patients with ER-positive/HER2-negative early breast cancer, who are at intermediate or high risk of disease recurrence. CAMBRIA-1 is comparing 5 years of camizestrant versus endocrine therapy in patients who have already received 2-5 years of standard endocrine therapy, with or without cyclin-dependent kinase 4/6 inhibitors, and are without recurrence. CAMBRIA-2 is comparing 7 years of upfront adjuvant camizestrant versus endocrine therapy, with abemaciclib permitted in both treatment arms for the first 2 years. The primary endpoint for both studies is invasive breast cancer-free survival. Secondary endpoints include invasive disease-free survival, distant recurrence-free survival, overall survival, pharmacokinetics, patient-reported outcomes, safety and tolerability.Tweetable abstract: CAMBRIA-1 and CAMBRIA-2 are ongoing, randomized, open-label trials of adjuvant camizestrant, either as an upfront treatment or as a treatment after standard endocrine therapy, in patients with HR+/HER2- early breast cancer at intermediate to high risk of disease recurrence.Clinical Trial Registration: NCT05774951 (CAMBRIA-1); NCT05952557 (CAMBRIA-2).
Keywords: Breast; clinical trials; drug development; hormonal therapy; women’s health.
Why will we perform this study? People with early-stage breast cancer in which the cancer cells have receptors for the hormones estrogen and/or progesterone are typically treated with standard endocrine therapies, which are cancer treatments that remove or block hormones. After surgery, endocrine therapies such as tamoxifen, anastrozole, letrozole or exemestane, are usually given for at least 5 years to prevent the breast cancer from returning and may be given for longer to high-risk patients. While this is currently the recommended treatment, it does not prevent cancer from returning in everyone. Camizestrant is a drug that blocks and degrades estrogen receptors in cancer cells, reducing their growth and spread. Previous research has already shown that camizestrant is more effective at delaying the growth and spread of advanced-stage breast cancer than fulvestrant, a currently approved treatment option for advanced-stage disease. Here, we describe the two CAMBRIA studies, which will test whether camizestrant is more effective than standard endocrine therapy at preventing breast cancer from returning in participants with early-stage disease.How will we perform this study? In CAMBRIA-1, participants who have completed surgery and have been receiving adjuvant endocrine therapy for 2–5 years will be treated for 5 years with either camizestrant or a continuation of standard endocrine therapy. In CAMBRIA-2, participants who have completed surgery and received little or no prior endocrine therapy will be treated for 7 years with either camizestrant or standard endocrine therapy, with or without abemaciclib. Both studies will assess whether camizestrant increases the length of time participants live without their breast cancer returning. The studies will also assess how long participants live after receiving camizestrant compared with those who receive standard endocrine therapy, and how well participants cope with treatment side effects. The number of participants expected to receive study treatment is approximately 4300 in CAMBRIA-1 and approximately 5500 in CAMBRIA-2.