Merck's Keytruda shows potential in aggressive breast cancer

Merck & Co's PD-1 inhibitor Keytruda could add breast cancer to its list of uses if early-stage data are backed up in further studies.

A Phase Ib trial of Keytruda (pembrolizumab) in patients with advanced triple-negative breast cancer - a particularly aggressive form of the disease - showed that the drug achieved an overall response rate of 18.5 per cent (five of 27) patients.

Moreover, among the responding patients the median duration of response had not been reached, even though three of them had been treated for 11 months or more. The result was particularly impressive as most of the patients enrolled into the trial had been treated with multiple rounds of chemotherapy.

Triple-negative breast cancer is the term given to tumours that do not express either the HER2, oestrogen or progesterone receptors, which means it will not respond well to hormonal therapies such as tamoxifen or aromatase inhibitors or those that target HER2 such as Roche's Herceptin (trastuzumab).

It is estimated that 10-20 per cent of all cases of breast cancer are triple-negative, and while therapies have transformed outcomes for many women with other forms of the disease, there remain few treatment options for this group.

"Metastatic, triple-negative breast cancer is an aggressive and often difficult to treat disease," said Rita Nanda of the University of Chicago, the principal investigator in the trial who is presenting the data today at the San Antonio Breast Cancer Symposium (SABCS).

Phase II trial in HER2-positive tumours

The results presage a major effort by Merck to expand the use of Keytruda into breast cancer, which until recently was not considered a particularly promising target for the PD-1 inhibitors.

The company has just announced a new phase II trial called PANACEA that aims to see whether adding Keytruda to treatment with Herceptin can restore susceptibility to Roche's drug in patients whose tumours are starting to exhibit resistance to the HER2-targeting drug.

"Traditionally, breast cancer has not been thought as an 'immunogenic' solid tumour, which is why immunotherapies have been initially evaluated in melanoma and renal cancers," said Fabrice André of the Institut Gustave Roussy in France, one of the principal investigators for the study.

"However, a significant amount of preclinical and correlative clinical data suggest that HER2-positive breast cancer could be amenable to immuno-therapeutic approaches," he added.

The primary objective of the trial is to determine the correct doe of Keytruda alongside Herceptin, while secondary endpoints include safety and efficacy measures including progression-free survival and overall survival. It is due to report top-line results in July 2017.

Keytruda is already approved in the US as a treatment for melanoma and was launched in September, and is also in clinical development for non-small cell lung cancer (NSCLC), bladder cancer and head and neck cancer, as well as haematological cancer such as Hodgkin lymphoma.