> Adding dalpiciclib to fulvestrant lengthens time without progression by 8 months

Adding dalpiciclib to fulvestrant lengthens time without progression by 8 months

  • 7 Min. Read
  • 06/09/21

New CDK 4/6 inhibitor improves progression free-survival over fulvestrant alone in people with hormone receptor-positive, metastatic breast cancer that progressed on previous hormonal therapy

A new CDK 4/6 inhibitor was presented on June 5 as part of the ASCO Annual Meeting and is likely to add a fourth option in this class of targeted therapies for hormone receptor-positive breast cancer.

The DAWNA-1 trial showed that dalpiciclib given with the hormonal therapy fulvestrant (Faslodex) to people with hormone receptor-positive, HER2-negative, metastatic breast cancer lengthened the time they went without cancer progressing compared to fulvestrant alone.


Cyclin-dependent kinase 4/6 inhibitors, known commonly as CDK 4/6 inhibitors, target two specific kinases, or proteins, called CDK 4 and 6. These kinases signal cancer cells to grow and divide, but CDK 4/6 inhibitors stop those signals and slow the growth of cancer. There are three CDK 4/6 inhibitors approved in the last 6 years to treat hormone receptor-positive, HER2-negative, metastatic breast cancer. Palbociclib (Ibrance) was the first medicine of this type approved to treat breast cancer in February 2015.

Dalpiciclib is CDK 4/6 inhibitor that has shown signs of action against cancer in early studies and has proven to be safe, according to presenter Binghe Xu, MD. It is given as a daily pill for 3 weeks with a 1-week break until progression.

The DAWNA-1 trial randomly assigned participants to one of two treatments:

  • 240 people were given dalpiciclib and fulvestrant.
  • 120 people were given placebo and fulvestrant.

The primary endpoint, the main measurement researchers used to determine if dalpiciclib worked better than a placebo, was progression-free survival, or how long before the cancer started growing again.


The DAWNA-1 trial found that the group given dalpiciclib and fulvestrant had a median progression-free survival more than twice as long as the group given placebo and fulvestrant:

  • Median progression-free survival for the dalpiciclib group was 15.7 months.
  • Median progression-free survival for the placebo group was 7.2 months.

The difference was statistically significant, meaning it was likely not a result of chance.

Researchers also noted that a year after starting the trial, people given dalpiciclib were less likely to have started chemotherapy as a later treatment:

  • 70.8 percent of people given dalpiciclib had not started chemotherapy.
  • 52.4 percent of people given placebo had not started chemotherapy.

The trial did not yet have data on the effect of dalpiciclib on overall survival, or the likelihood of dying of any cause during the studied period. Overall survival is an important measure of a medicine’s effect, but it takes longer to see effects on overall survival.

Dalpiciclib lead to more cases of grade 3 and 4 side effects, meaning they required medical attention, than did the placebo. Most of the side effects overall and most of the grade 3 and 4 side effects were decreases in certain types of cells in the blood, specifically neutropenia, anemia, and leukopenia.

Other side effects included high levels of certain liver enzymes and nausea, and almost all of those cases were grade 1 or 2. The rate of people stopping treatment due to side effects was higher in the placebo group than in the dalpiciclib group:

  • 2.5 percent of people given dalpiciclib stopped the trial treatment due to side effects.
  • 3.3 percent of people given placebo stopped the trial treatment due to side effects.

What this means for you

If approved by the Food and Drug Administration, dalpiciclib would be the fourth CDK 4/6 inhibitor approved to treat hormone receptor-positive breast cancer. These medicines have become a standard part of treatment after demonstrating effects like those seen in the DAWNA-1 trial. Discussant Otto Metzger, MD, describes the 8-month difference in progression-free survival a “dramatic improvement.”

The CDK 4/6 inhibitors are very similar and can be used interchangeably with fulvestrant in this setting, but there are differences that can affect your care. In a discussion of the DAWNA-1 trial and two others presented at the ASCO Annual Meeting, Dennis Slamon, MD, says researchers are learning more about these medicines and the specific side effects and features that may lead your doctor to recommend one over the others. Dalpiciclib may add yet another option to this important group of medicines.