Results of an interim analysis from the KEYNOTE-522 trial have shown a treatment combination of immunotherapy plus chemotherapy to improve response rates in patients with early triple-negative breast cancer (TNBC). The trial, led by Professor Peter Schmid, Lead for the Centre for Experimental Cancer Medicine (Barts Cancer Institute, Queen Mary University of London), is the first phase III immunotherapy trial in early breast cancer.

The interim results of the KEYNOTE-522 trial were presented on 29^th September by Professor Schmid at the ESMO Congress 2019 in Barcelona, Spain.

An aggressive and difficult-to-treat cancer

TNBC accounts for approximately 15% of all breast cancer cases and is more likely to affect younger people. This breast cancer subtype is characterised by the absence of receptors for the hormones oestrogen and progesterone, and receptors for the HER2 protein. Therefore, hormone therapy and drugs that work by targeting these receptors are ineffective against TNBC.

Patients with TNBC typically receive chemotherapy, followed by surgery to remove the tumour. This provides the best chance of pathological complete response (no trace of cancer in tissue samples following therapy and surgery).

KEYNOTE-522 investigated whether adding pembrolizumab, an immunotherapy, to chemotherapy in a neoadjuvant setting (i.e. administered prior to surgery to remove the tumour) could improve pathological complete response and event-free survival in women with early TNBC. In the trial, funded by Merck, patients were treated with either immunotherapy plus chemotherapy or placebo plus chemotherapy.

The analysis presented at the ESMO Congress 2019 was performed on 602 evaluable patients after a median follow-up of 15.5 months. The patients treated with the pembrolizumab-chemotherapy combination exhibited a significant improvement in pathological complete response compared with that seen in patients who received the placebo (64.8 vs 51.2%, respectively). An improvement in event-free survival was also observed in patients who received the immunotherapy combination treatment.

Speaking of the trial, Professor Schmid said:

"These are preliminary data, but they provide a strong sign that the addition of immune therapy to neoadjuvant chemotherapy prevents breast cancer recurrence. If we prevent recurrence, we cure more patients, but we need longer-term data for confirmation."

Pembrolizumab is an immune checkpoint inhibitor, which binds to a protein called PD-1 on the surface of immune cells. By blocking PD-1, pembrolizumab triggers immune cells to locate and kill cancer cells. Although immune checkpoint inhibitors have changed the treatment landscape for a variety of cancer types, they have previously been shown to be less effective in breast cancer.

Notably, KEYNOTE-522 is the first trial to show the success of an immune checkpoint inhibitor as a neoadjuvant treatment in breast cancer and the findings represent an important step forward for this aggressive, difficult-to-treat breast cancer subtype.

View the full abstract here.