What is the prognosis for a woman in her 40s with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), metastatic breast cancer (CA) with positive lymph nodes and a single sternal metastatic lesion, treated with ribociclib (generic name) and letrozole (hormone blocker)?

From the Guidelines

Metastatic breast cancer, particularly HR+/HER2- with distant metastasis (sternal lesion), is generally considered incurable with current standard treatments, and the primary goal of treatment is to control disease progression, extend life, and maintain quality of life. The oncologists' recommendation of ribociclib (a CDK4/6 inhibitor) combined with letrozole (an aromatase inhibitor) is the standard of care for this type of cancer, as supported by the MONALEESA-2 trial 1. This combination therapy has been shown to significantly improve progression-free survival (PFS) compared to hormone therapy alone, with a median PFS of approximately 25-33 months, as reported in the MONALEESA-2 trial 1 and the NCCN guidelines 1.

While complete cure is not the expected outcome, some patients can experience prolonged disease control lasting several years. The MONALEESA-2 trial found that the estimated PFS rate after 12 months in the ribociclib-letrozole arm was 82%, compared to 66% in the placebo-letrozole arm 1. Additionally, the MONALEESA-7 trial reported an improvement in overall survival (OS) with ribociclib, with 70% of patients alive at 3.5 years, compared to 46% in the placebo group 1.

It's essential to understand that while metastatic breast cancer is considered a chronic disease requiring ongoing treatment, some patients with limited metastatic disease (oligometastatic) may benefit from more aggressive approaches, including radiation or surgery to the metastatic sites, in addition to systemic therapy. For emotional support during this difficult time, connecting with support groups specifically for young mothers with cancer can be valuable, as can discussing palliative care options early to maintain quality of life throughout treatment. The patient's quality of life should be prioritized, and treatment decisions should be made with consideration of the potential benefits and risks, as well as the patient's individual preferences and values.

Key points to consider in the treatment of metastatic breast cancer include:

• The use of CDK4/6 inhibitors, such as ribociclib, in combination with hormone therapy, as supported by the MONALEESA-2 trial 1 and the NCCN guidelines 1
• The importance of maintaining quality of life throughout treatment, as reported in the MONALEESA-2 trial 1
• The potential benefits of more aggressive approaches, including radiation or surgery, for patients with limited metastatic disease
• The need for ongoing support and discussion of palliative care options to maintain quality of life throughout treatment.

From the FDA Drug Label

The major efficacy outcome measure for the study was investigator-assessed progression-free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST) v1. 1. The efficacy results are summarized in Table 19, Figure 2 and Figure 3. Table 19: Efficacy Results – MONALEESA-2 (Investigator Assessment, Intent-to-Treat Population) KISQALI + LetrozolePlacebo + Letrozole Progression-Free SurvivalN = 334N = 334 Events (n, %)93 (27. 8)150 (44.9) Median (months, 95% CI)NR (19.3 – NR)14.7 (13.0 – 16.5) Hazard Ratio (95% CI)0.556 (0.429,0.720) p-value< 0.0001

The treatment with ribociclib and letrozole is not curative for HR+/HER2- metastatic breast cancer. The primary goal of this treatment is to prolong progression-free survival (PFS) and overall survival (OS).

• PFS is the length of time during and after treatment that a patient lives with the disease but it does not get worse.
• OS is the length of time from either the date of diagnosis or the start of treatment that patients are still alive. According to the study results, the combination of ribociclib and letrozole has been shown to significantly improve PFS and OS compared to letrozole alone in patients with HR+/HER2- advanced or metastatic breast cancer. However, the drug label does not provide information on the possibility of a cure for this type of cancer with this treatment regimen 2.

From the Research

Treatment Options for HR+/HER2- Metastatic Breast Cancer

• The patient in question has been diagnosed with HR+/HER2- metastatic breast cancer, with positive lymph nodes and a single sternal metastatic lesion.
• Two oncologists have recommended a palliative approach, with a treatment plan consisting of ribociclib and a hormone blocker (letrozole) 3, 4, 5, 6, 7.

Efficacy of Ribociclib and Letrozole

• Studies have shown that the combination of ribociclib and letrozole can significantly improve progression-free survival (PFS) and overall survival (OS) in patients with HR+/HER2- advanced breast cancer 3, 4, 5, 6, 7.
• The MONALEESA-2 trial demonstrated a median PFS of 25.3 months with ribociclib plus letrozole, compared to 16.0 months with placebo plus letrozole 5.
• The overall survival benefit of ribociclib plus letrozole was also significant, with a median OS of 63.9 months, compared to 51.4 months with placebo plus letrozole 3.

Safety and Tolerability

• The safety profile of ribociclib plus letrozole has been evaluated in several studies, with common adverse events including neutropenia, increased liver enzymes, and QTc prolongation 6, 7.
• The CompLEEment-1 trial reported a manageable safety profile for ribociclib plus letrozole in a broad population of patients with HR+/HER2- advanced breast cancer, with a median follow-up of 26.97 months 7.

Patient Selection and Special Considerations

• Patient selection for ribociclib plus letrozole should take into account factors such as age, liver function, and cardiac risk factors 6.
• The use of ribociclib plus letrozole may be beneficial in patients with HR+/HER2- advanced breast cancer, including those with visceral metastases and prior chemotherapy 7.