- Adding the CDK4/6 inhibitor ribociclib to endocrine therapy resulted in a significant improvement in invasive disease–free survival for patients with hormone receptor–positive, HER2-negative early-stage breast cancer
- Findings from this phase III NATALEE trial were presented at the 2023 ASCO Annual Meeting (Abstract LBA500)
- Hormone receptor–positive, HER2-negative breast cancer:
- Is the most common subtype of the disease:
- Making up nearly 70% of all breast cancer cases in the United States
- Roughly one-third of patients with stage II hormone receptor–positive, HER2-negative disease:
- Experience a recurrence following standard-of-care treatment
- More than one-half of patients with stage III hormone receptor–positive, HER2-negative disease:
- Experience a recurrence
- Is the most common subtype of the disease:
- If a recurrence occurs:
- It is often at a more advanced stage
- Ribociclib is currently approved by the U.S. Food and Drug Administration to treat:
- Hormone receptor–positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor for premenopausal patients or in combination with fulvestrant for postmenopausal patients
- While ribociclib has previously shown survival benefits in people with metastatic disease:
- In the NATALEE study, researchers showed that it may also improve outcomes for people with earlier-stage disease, including those with cancer that has not yet spread to the lymph nodes
- The NATALEE phase III clinical trial:
- Included men and premenopausal or postmenopausal women from 20 different countries with stage IIA, IIB, or III hormone receptor–positive, HER2-negative breast cancer who were at risk for disease recurrence
- Participants were randomly assigned to receive either 400 mg of adjuvant ribociclib for 3 years with hormonal therapy for at least 5 years (n = 2,549) or hormonal therapy alone for at least 5 years (n = 2,552)
- Men and premenopausal women also received Goserelin
- Prior hormonal therapy use was allowed if it was initiated no more than 1 year before the start of the study
- The current recommended starting dose of ribociclib for people with metastatic disease is 600 mg:
- However, an extended duration of treatment may help to stop cells from duplicating and dividing and destroy any remaining cancer cells:
- Because of this, study authors chose a 3-year treatment duration of ribociclib at a dose of 400 mg to reduce side effects while maintaining efficacy
- However, an extended duration of treatment may help to stop cells from duplicating and dividing and destroy any remaining cancer cells:
- Key Findings:
- At a median follow-up of 34 months:
- 20.2% of participants in the ribociclib group had completed 3 years of treatment
- 56.8% had completed 2 years of treatment
- Overall, 74.7% of participants remained on study treatment at data cutoff, with 1,984 patients on ribociclib and 1,826 patients on hormonal therapy alone
- The study found that adding ribociclib to hormonal therapy:
- Led to a significant improvement in invasive disease–free survival compared with hormonal therapy alone:
- Researchers evaluated invasive disease–free survival after 426 invasive disease–free survival events occurred, a number that was prespecified for the interim analysis
- Of those events, 189 occurred in the ribociclib group (7.4% of patients) vs 237 in the hormonal therapy alone group (9.2% of patients)
- The 3-year invasive disease–free survival rates were:
- 90.4% in the ribociclib group compared with 87.1% in the hormonal therapy alone group
- Overall, the addition of ribociclib reduced the risk of disease recurrence by:
- 25%
- The invasive disease–free survival benefit seen in the ribociclib group was generally consistent across clinically relevant patient subgroups
- Ribociclib also showed more favorable outcomes in overall survival, recurrence-free survival, and distant disease–free survival
- For patients receiving ribociclib, the most common adverse effects were:
- Neutropenia and joint pain
- Rates of gastrointestinal adverse effects and fatigue were low in patients receiving ribociclib
- For patients receiving hormonal therapy alone, the most common adverse effects were:
- Joint pain and hot flash.
- At a median follow-up of 34 months:
- Currently approved targeted treatments can only be used in a small population of patients diagnosed with hormone receptor positive, HER2-negative early breast cancer:
- Leaving many without an effective treatment option for reducing risk of the cancer returning:
- Thus, there is a significant unmet need for both reducing the risk of recurrence and providing a tolerable treatment option that keeps patients cancer-free without disrupting their daily life:
- The NATALEE study investigated the addition of ribociclib to standard-of-care adjuvant endocrine therapy and was specifically designed to address these unmet needs
- Thus, there is a significant unmet need for both reducing the risk of recurrence and providing a tolerable treatment option that keeps patients cancer-free without disrupting their daily life:
- Leaving many without an effective treatment option for reducing risk of the cancer returning:
Rodrigo Arrangoiz MS, MD, FACS, FSSO 