Palbociclib failed to improve outcomes in early-stage disease

Presented on December 7 at the San Antonio Breast Cancer Symposium, the findings show that palbociclib does not improve outcomes for people with early-stage hormone-positive (HR+) HER2- breast cancer.  

Preliminary findings of the trial were published in Lancet in July. The results were released concurrent with this week’s presentation in the Journal of Clinical Oncology.  

Background 

Now that researchers have seen how effective CDK inhibitors can be in metastatic breast cancer, they wanted to explore whether these medicines could work at preventing people with early-stage disease from a breast cancer recurrence. Palbociclib Collaborative Adjuvant Study (PALLAS) is among several studies asking that question.  

CDK inhibitors are a form of targeted therapy used to treat metastatic breast cancer. Many people prefer targeted therapy medicines because they cause fewer side effects than chemotherapy and often can be taken in pill form.  

CDK 4/6 inhibitors work by stopping cells from growing and dividing. The introduction of CDK 4/6 drugs in 2015 filled a gap in treatment options for HR+/HER2- breast cancer, particularly metastatic breast cancer.  

Endocrine (or hormone) therapy is a standard treatment after surgery for hormone-positive breast cancer. Different medicines of this type are available.  

Results 

The PALLAS phase III trial randomized participants to two groups – one that received palbociclib along with hormone (endocrine therapy). The other (control) group received endocrine therapy on its own.  

The average age of people in the trial was 52. Most had stage IIB or stage III breast cancer. All had ER+/HER2- breast cancer. Eighty-five percent were previously treated with chemotherapy. Fifty-nine percent were considered high risk. The average time at follow up was 31 months.  

After two years, the people in both groups had nearly the same results across all endpoints. 

Some participants appeared to improve initially but the data did not hold up. There were no differences in subgroups. No new side effects were identified.  

The clinical trial itself drew praise for its size and organization. Within three years, investigators exceeded trial goals by recruiting 5,800 participants at 406 centers in 21 countries. 

What it means for people with early-stage disease 

Based on these results, there is no reason to prescribe palbociclib in combination with endocrine therapy after surgery for early-stage HR+ breast cancer. Endocrine therapy alone is still recommended.  

The results of this study were both confusing and disappointing to the research community. It is unclear why these findings differed from the results of other trials of CDK inhibitors, particularly the monarchE trial, which reported favorable preliminary results this year. 

The phase III monarchE trial tests the CDK 4/6 inhibitor abemaciclib with endocrine therapy for early-stage HR+/HER2- disease. It is similar in size and scope to the PALLAS trial. The drugs themselves work similarly.

Looking for differences, the study team noted that the dose schedule is not the same. Abemaciclib in the monarchE trial is taken without a break, whereas palbociclib was given on a three weeks on/one week off schedule. The lead investigator was not prepared to say the differences in outcomes were due to this but suggested it bears further study. 

The PALLAS results do not have implications for metastatic breast cancer although it was noted that no new or worsening side effects were observed.  

Look for further studies to address unanswered questions.