A trial looking at palbociclib and letrozole before breast cancer surgery (PALLET)

The trial team found that palbociclib and letrozole didn’t shrink the cancer more. The researchers think this might be because it takes longer than 14 weeks for the cancer to get smaller. But they did find more cancer cells that had died in the women who had the combined treatment.

And they found that palbociclib and letrozole helped to stop cancer cells dividing as fast than the letrozole on its own.

Trial design
This was a phase 2 trial. 307 women took part. They were put into 1 of 4 treatment groups at random. They had treatment as follows:

• 103 had letrozole on its own
• 68 had letrozole for 2 weeks followed by letrozole and palbociclib for the next 12 weeks
• 69 had palbociclib for 2 weeks followed by letrozole and palbociclib for the next 12 weeks
• 67 letrozole and palbociclib for 14 weeks

For every 3 women in group A, there were 2 women in group B, group C or group D.

PALLET randomisation diagram

The women gave blood samples and tissue samples (biopsies) from the breast cancer:

• just before the start of treatment
• 2 weeks after starting treatment
• when treatment finished

The trial team used these samples to find out:

• how quickly cancer cells were dividing (this is called cell proliferation)
• the number of cancer cells which die (this is called apoptosis) and are no longer able to divide
• if the cancer had shrunk 
• if the type of surgery the women had changed from removing the whole breast (mastectomy ) to removing the breast cancer only (breast conserving surgery)

Results
253 patients completed 14 weeks of treatment prior to their planned surgery. 

The trial team looked at how treatment affected how quickly cells divided. This is called cell proliferation. They did a number of calculations. They found that having palbociclib and letrozole worked better than letrozole to stop the cells dividing as quickly. 

They also looked at how many women had cancer cells that died and could no longer divide. This happened in:

• 9 out of 10 women (90%) who had palbociclib and letrozole
• just under 6 out of 10 women (59%) who had letrozole on its own

At the end of the trial they checked how much the cancer had shrunk by half or had completely disappeared. This is a partial or complete response. They found this was:

• about 54 out of every 100 women (54%) who had letrozole and palbociclib
• just under 50 out of every 100 women (49.5%) who had letrozole on its own

Although these numbers look a bit different, the difference wasn’t significant. This means it could have happened by chance. 

The researchers didn’t find a difference between the groups in how many women had their planned surgery changed from removing the whole breast, to removing the cancer area only.

Side effects
The researchers say that most of the side effects were mild to moderate. 

Women who had palbociclib and letrozole had more problems with a drop in the number of white blood cells .

Conclusion
This trial showed that 14 weeks of treatment with palbociclib and letrozole worked better at slowing down how quickly the cancer cells divided compared to letrozole on its own.

There was no difference in the size of the cancer between the groups at the end of 14 weeks of treatment. But the researchers think that this is because it may take much longer than 14 weeks for the cancer to get smaller in size with treatment.

All trial results help doctors and researchers understand more about different cancers and the best way to treat them. 

Where this information comes from
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed ) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.