The PACE clinical trial found that adding palbociclib to fulvestrant yielded no benefit over fulvestrant alone in people with metastatic hormone receptor-positive, HER2-negative breast cancer whose cancer grew after treatment with a CDK 4/6 inhibitor drug. Notably, the study found possible benefit from adding immunotherapy. These results were presented at the 2022 San Antonio Breast Cancer Symposium on December 8.
CDK 4/6 inhibitors are standard treatment for metastatic HR+, HER2- breast cancer. They are given with hormonal, or endocrine, therapy. They can work well at controlling cancer growth for a while and then stop working at some point, as the cancer becomes resistant to either the endocrine therapy, the CDK 4/6 inhibitor, or both. Today, it’s unclear whether people in this situation should continue taking the CDK 4/6 inhibitor. Early research has suggested that adding immunotherapy could bolster the combination therapy to work better.
The PACE clinical trial looks at the benefit of continuing the CDK 4/6 inhibitor with fulvestrant, instead of the endocrine therapy that had been given before. It also considers whether the adding immunotherapy would help stop cancer growth.
PACE was a randomized controlled clinical trial that divided its 220 participants at 13 U.S. cancer centers into three groups. All participants had metastatic HR+, HER2- breast cancer that started to grow or spread while they were taking a CDK 4/6 inhibitor and endocrine therapy. Before entering the trial, the participants had gone at least six months without cancer progression on the CDK 4/6 inhibitor.
This study involved three different kinds of drugs:
- Fulvestrant (Faslodex), an endocrine or hormonal therapy not previously taken by study participants
- Palbociclib (Ibrance), one of three CDK 4/6 inhibitors approved to treat metastatic breast cancer
- Avelumab (Bavencio), a type of immunotherapy called a checkpoint inhibitor (also a monoclonal antibody) that works against PD-L1 and is FDA approved to treat other kinds of cancer
The study had three groups, or arms. Depending on the arm, participants received
- Fulvestrant only (55 participants)
- Fulvestrant and palbociclib (111 participants)
- Fulvestrant, palbociclib, and avelumab (54 participants)
The primary aim was to compare fulvestrant to fulvestrant plus palbociclib. A secondary goal was to look at the combination of fulvestrant/palbociclib/avelumab.
The results showed no benefit for palbociclib plus fulvestrant over fulvestrant alone. In both groups, people on average saw their cancer progress beginning at 4.6 to 4.8 months. The group receiving all three forms of therapy had a longer period without cancer growth, at 8.1 months. After one year, this triple-drug combination worked to hold off cancer in 35.6% of people, compared to 17.5% in the fulvestrant only group and 13.1% in the fulvestrant plus palbociclib group. These results reflect findings after a median follow-up of 23.6 months.
The groups in this study were small but the findings suggest continuing a CDK inhibitor with endocrine therapy after disease growth won’t improve disease control but may increase side effects. The immunotherapy findings will be further studied, as researchers are interested in seeing whether this type of treatment could benefit people with hormone receptor-positive metastatic breast cancer.
What this means for you
If you are taking palbociclib or any CDK 4/6 inhibitor for metastatic breast cancer, talk with your doctor about how the cancer is responding to the medicine. In general, if a medicine is working and the side effects are tolerable, doctors usually advise continuing with it.
CDK 4/6 inhibitors were the source of significant buzz at SABCS 2022 due in part to inconsistent clinical trial findings. Notably, the MAINTAIN study showed the benefit of ribociclib (Kisqali) plus endocrine therapy among a similar patient population as this PACE trial. You may want to ask your doctor about this medicine as well.
In this study of palbociclib, there were some “trends” that were not statistically significant (meaning they could have happened by chance) but that may warrant further study. For example, people who were identified as “endocrine-resistant” benefited somewhat from staying on palbociclib. Also, adding immunotherapy to the combination of palbociclib and fulvestrant shows promise but needs more study.
Our 2022 SABCS coverage
- Abemaciclib, everolimus studied in high-risk, early-stage HR-positive breast cancer
- Enhertu continues to show good results
- POSITIVE news about pregnancy and breast cancer
- Strengthening cancer care through communication
- Elacestrant on course to gain FDA approval
- Talking about racial disparities, pushing for solutions
- New breast cancer drug targets AKT pathway
- Research looks to avoid overtreatment in early-stage breast cancer
- Sexual side effects matter to young women
- Babytam effective in preventing breast cancer
Sign up to receive emotional support, medical insight, personal stories, and more, delivered to your inbox weekly.