Merck & Co's Keytruda fails in triple negative breast cancer trial

Most of the time, Merck & Co’s Keytruda (pembrolizumab) has been a consistent performer across a range of cancers – but it has produced an uncharacteristic failure in tough to treat triple negative breast cancer.

US-based Merck tested Keytruda, an anti-PD-1 immunotherapy, as monotherapy in second or third line in patients with metastatic triple negative breast cancer (TNBC).

This is a rare form of the disease that lacks the three most common receptors found on the disease, which interact with the hormones oestrogen, progesterone and human epidermal growth factor 2 (HER2).

Results of the phase 3 KEYNOTE-119 trial showed Keytruda missed its primary endpoint by failing to improve overall survival compared with standard chemotherapy – capecitabine, eribulin, gemcitabine or vinorelbine.

The study randomised 622 patients to receive either Keytruda as monotherapy (200 mg fixed dose every three weeks for up to 24 months) or a physician’s choice of single-agent chemotherapy at a ratio of 1:1.

Other endpoints were not formally tested per the study protocol because the primary endpoint of overall survival was not met, although there were no new surprises in terms of Keytruda’s safety.

The US pharma is testing several chemotherapy and Keytruda cocktails in TNBC patients in the KEYNOTE-522 trial.

This trial started in 2017, and initial results are expected soon and could potentially lead to approval as a neoadjuvant therapy administered before an operation, or as an adjuvant to hit remaining disease after surgery.

Until earlier this year there were no immunotherapies approved at all in triple negative breast cancer, leaving patients with chemotherapy as the only treatment option.

But in March Roche’s Genentech unit got its Tecentriq (atezolizumab) approved in combination with Celgene’s Abraxane (nab-paclitaxel) in TNBC patients whose locally advanced or unresectable tumours express the protein PD-L1.

Roy Baynes

Merck & Co’s head of global clinical development, Dr Roy Baynes, said: “While we are disappointed by the outcome of this monotherapy trial, we are continuing to study Keytruda in earlier stages of the disease and in combination with chemotherapy to address the unmet medical need of patients with triple negative breast cancer. We are grateful to the patients and investigators for their participation in this important study.”