Comparing the safety of palbociclib combined with fulvestrant or letrozole in HR+/HER2- advanced breast cancer

This study evaluated the safety profile of palbociclib (Ibrance) combined with either fulvestrant (Faslodex) or letrozole (Femara) in patients with hormone-receptor-positive (HR+) and HER2 negative (HER2 -) advanced breast cancer (BC). The data showed that both palbociclib regimens were safe and tolerated in these patients with some rare side effects of venous thromboembolism (VTE) and interstitial lung disease (ILD).

Breast cancer (BC) is classified based on whether it has specific receptors (proteins that are located on cancer cells). HR+ BC means cancer cells grow in response to female sex hormones (estrogen/progesterone). HER2- means cancer cells do not have the HER2 protein on their surface and do not grow in response to this protein. HER2 (human epidermal growth factor receptor 2) is a protein that can be found on breast cells. About 70% of BCs are HR+ and HER2-. One treatment option for patients with this subtype of BC is palbociclib combined with either fulvestrant or letrozole.

Palbociclib is targeted or biological therapy. It blocks proteins CDK4 and CDK6 which results in stopping or slowing down the growth of breast cancer cells. Fulvestrant and Letrozole are hormone therapies that block the effects of estrogen, leading to the slow growth of cancer cells. Previous studies have shown that palbociclib with fulvestrant or letrozole has improved the outcomes of patients with HR+/HER2- advanced BC. However, the safety and toxicity of these palbociclib regimens are not completely clear.

The study included 486 patients with advanced BC. Half of the patients received fulvestrant–palbociclib (FP) and the other half received letrozole–palbociclib (LP). Side effects were evaluated. The average treatment duration was 23.9 months in the FP group and 25.2 months in the LP group. The average follow-up period was 32.3 months. 

99.6% of the FP group and 99.2% of the LP group experienced side effects. However, most of the side effects were mild and manageable.

Serious side effects were less common in the LP group (21.1%) compared to the FP group (29.9%). In both groups, the most common side effects reported were low blood cell counts, tiredness, joint pain, and diarrhea. 

Venous thromboembolism (VTE) is a condition that involves a blood clot forming in a deep vein. VTE was seen in 5.8% of the FP group and 4.5% of patients in the LP group. This difference was not statistically significant. Pulmonary thromboembolism (PTE) is a more serious form of VTE that involves the clot going to the lungs. PTE occurred in 5% of patients in the FP group and 2.5% of the LP group.

Interstitial lung disease (ILD) involves damage to the inner parts of the respiratory system. It can lead to scarring of the lungs and breathing problems. 50% of both groups reported some grade of ILD. Serious ILD occurred in 2.5% of patients in both groups.

The study concluded that palbociclib with either fulvestrant or letrozole was considered safe and well tolerated in patients with HR+/HER2- advanced BC, with low occurrence rates of VTE and ILD.

The study was funded by Pfizer, the manufacturer of palbociclib.