News > Ribociclib on track for approval for early-stage breast cancer | ASCO 2023

Ribociclib on track for approval for early-stage breast cancer | ASCO 2023


If approved, ribociclib will be the second CDK 4/6 inhibitor approved for early-stage HR+, HER2- breast cancer. Abemaciclib (Verzenio), already FDA approved for early-stage disease, is also the focus of continued study. New results presented in the same session confirm that abemaciclib’s benefit in early-stage disease persists over time and that the drug is safe and effective for adults over 65.


HR+, HER2-negative breast cancer is the most common form of breast cancer. When found early, treatment involves surgery and anti-estrogen therapy, sometimes with chemotherapy and radiation therapy. People often end treatment and are told they are cured. Yet, the cancer can come back, sometimes even decades later. Doctors continue to try to understand which cancers will return so they can prevent recurrence.

CDK 4/6 inhibitors are a newer class of targeted therapy focused on the kinases CDK4 and CDK6 that help cancer cells grow and divide. Three CDK 4/6 inhibitors are approved to treat metastatic HR+, HER2- breast cancer. The three drugs–abemaciclib, palbociclib (Ibrance), and ribociclib–work in similar ways. Doctors first thought they were interchangeable, but clinical trials have revealed differences in side effects and benefit. Until now, only abemaciclib had been proven effective in treating early-stage disease.


Ribociclib reduced risk of recurrence by 25% and risk of metastatic disease by 26% in people with early-stage HR+, HER2- breast cancer. Prior research found that ribociclib extended both time without cancer growth and survival in advanced breast cancer of this type. This study, NATALEE, is the first study showing benefit in early-stage disease.

The phase III, randomized, open-label NATALEE clinical trial included more than 5,100 people with stage IIa, stage IIb, or stage III breast cancer. The trial was open to men and pre- or post-menopausal women who had lymph node-positive or -negative disease. Half of participants had past anti-estrogen therapy or chemotherapy. The results reported here represent an average of almost 28 months of follow-up.

The study compared participants who took ribociclib plus a non-steroidal aromatase inhibitor (NSAI)–either letrozole (Femara) or anastrozole (Aromasin)–to those who received only the NSAI. Men and premenopausal women also took goserelin.

The study tested a smaller dose of ribociclib than used previously. Participants took 400 mg of ribociclib instead of the 600 mg dose used to treat metastatic disease. The lower dose was both effective and safe, reducing QT prolongation–a serious heart rhythm disorder that is a rare side effect of ribociclib–more than sixfold. Other common side effects included neutropenia, joint pain, nausea, headache, liver problems, and fatigue. Most side effects appeared within four months of starting the medicine.

The addition of ribociclib also shows a positive trend for overall survival, but it is too early to report on those results. The study continues to follow participants, so look for more data to come.

Results of monarchE, presented in the same session, found that the drug’s benefit has continued beyond the initial study period. At four years, abemaciclib reduces risk of either recurrence or metastasis by 34%. The new analysis also found that abemaciclib was equally effective in younger and older people (under and over 65 years of age). Older people had similar side effects but were more likely to experience more serious diarrhea and fatigue. They were also more likely to stop the medicine or reduce their dose.

What does this mean for you?

If you have early-stage HR+, HER2- breast cancer, you may soon have a new treatment option to prevent cancer from coming back. The results of this trial will likely lead to FDA approval. Ribociclib will join abemaciclib as the second CDK 4/6 inhibitor approved for this use. While abemaciclib is only approved for high-risk cancers of this type, ribociclib was studied in a broader group.

If you are considering these drugs, talk with your doctor about the risks and benefits. These medicines work in similar ways but have different dosing schedules. Abemaciclib is taken consistently, whereas breaks are included in the administration of ribociclib. We know more about the ongoing benefit of abemaciclib for early-stage disease and its effectiveness, specifically for older adults.

The serious side effects differ somewhat. Both drugs can cause neutropenia. Ribociclib also brings a risk of liver problems and the rare but notable QTc prolongation side effect. The risk of the latter is even lower with the dose used for early-stage disease.

One of the key takeaways of these trials relates to dose. In trials of CDK 4/6 inhibitors, people often stop taking the medicine rather than trying a lower dosage. The abemaciclib trial found that people who took a lower dose in response to side effects still saw a benefit from the medicine. If you are experiencing side effects from a cancer drug that is working or likely to work, talk with your doctor about the dose. You may be able to try a lower dose before moving on to another treatment.


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