A trial looking at the effect of having trastuzumab or lapatinib before surgery on early breast cancer (EPHOS B)

The trial team found that having trastuzumab and lapatinib before surgery led to changes in the cells for many women with HER2 positive breast cancer. 

Trial design
This was a phase 2 trial. 257 women took part.

It was a randomised trial. The women who took part were put into treatment groups. Neither they nor their doctor could choose which group they were in.

There were 2 parts to this trial.

Part 1

To start 130 women were put into one of the following groups:

• no treatment before surgery (control group )
• trastuzumab starting 11 days before surgery 
• lapatinib starting 11 days before surgery
   

EPHOS B- Randomisation part 1

Part 2
During the trial the results of other trials were published. These results showed that combining trastuzumab with lapatinib worked well for HER2 positive breast cancer. So the trial team changed the groups in EPHOS-B to include this.  

127 women were put into:

• no treatment before surgery (control group)
• trastuzumab starting 11 days before surgery
• trastuzumab and lapatinib starting 11 days before surgery

EPHOS B- Randomisation part 2

The researchers looked for any changes trastuzumab and lapatinib had on breast cancer cells. To do this they looked at samples of tissue taken when the women were first diagnosed. They then compared these with a sample of tissue removed during surgery.

In the laboratory they tested the tissue samples to see if there had been a drop in the levels of a particular protein. This protein is called Ki67. This tells researchers how fast cells multiply and increase. They also looked to see if there had been an increase in the levels of another protein which gives them information about the cells dying. 

Results
The trial team were able to look at the level of the Ki67 protein in a total 223 women across both parts.

In part 1 they had the results for 115 women. They found the level of Ki67 at surgery was at least 30% lower in:

• 29 out of 44 women (66%) who had lapatinib
• 18 out of 49 women (37%) who had trastuzumab
• 1 out of 22 women (5%) who had no treatment

EPHOS B -Bar Chart 1

In part 2 they had the results for 108 women. They found that Ki67 at surgery was at least 30% lower in:

• 36 out of 49 women (74%) who had lapatinib and trastuzumab
• 14 out 31 women (45%) who had trastuzumab
• 2 out of 8 women (2%) who had no treatment

EPHOS B - Bar Chart 2

In the laboratory they looked at the tissue removed during surgery. They found that some women had no cancer left in the body after just 11 days of treatment. This is a pathological complete response. 

In part 1 they found that 1 woman had a complete response. They had trastuzumab.

In part 2 they found it was 1 woman in the trastuzumab group and 4 women in the lapatinib and trastuzumab group. 

The team looked whether trastuzumab and lapatinib increased cell death. They found that neither nor the combination of both did.

After a average follow up of 6 years the number of women whose cancer had come back was 28 out of 257. 

Conclusion
The trial team concluded that having a short course of trastuzumab and lapatinib before surgery could help some women. This is for those with HER2 positive breast cancer. 

They also say that finding out if this treatment works may help with decisions about what other treatment a person needs. This is a way of individualising treatment for those with HER2 breast cancer. 

They suggest that future trials for this group need to look at ways to reduce chemotherapy in some. They also suggest that there is a need to look at adding other treatments for those where this treatment works less well.  

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.