Study backs earlier use of Keytruda in cervical cancer

A phase 3 trial of Merck & Co’s checkpoint inhibitor Keytruda could support the expansion of its use in cervical cancer to include newly-diagnosed patients with less severe disease.

The results of the KEYNOTE-A18 trial found that adding Keytruda (pembrolizumab) to chemotherapy in newly-diagnosed patients with high-risk locally advanced cervical cancer extended the time to disease progression or death compared to chemo alone.

The study (also known as ENGOT-cx11/GOG-3047) recruited women who were receiving external beam radiotherapy, followed by brachytherapy, which is the standard treatment approach for this earlier-stage form of cervical cancer.

There was also a trend towards improved overall survival (OS), although Merck said the data on this endpoint is not yet mature and the trial will continue to see if it reaches statistical significance. It will present the full data at a future cancer conference and also plans to share the results with regulatory authorities.

The result is important, as the prognosis for women with locally-advanced cervical cancer remains fairly poor, with a five-year survival rate of approximately 65%, and more than half experience disease recurrence within two years.

Moreover, there are fears of an increase in cervical cancer cases if action is not taken to address low and declining cervical cancer screening participation rates in some countries, according to a white paper from the just-launched ACCESS expert group that is lobbying to reverse that trend.

KEYNOTE-A18’s lead researcher, Professor Domenica Lorusso of the Catholic University of Rome, said the results are encouraging, as there have been “limited new treatment advances for these patients beyond the current standard of care […] in the past 20 years.”

Keytruda is already approved by the FDA as a first-line therapy for PD-L1-positive metastatic cervical cancer in combination with chemo, with or without bevacizumab, and as a second-line therapy after patients with PD-L1-positive tumours have progressed despite chemo.

In Europe, Regeneron’s Libtayo (cemiplimab) is indicated as a second-line therapy for recurrent or advanced cervical cancer, regardless of PD-L1 expression status, but the drug’s filing in the US was withdrawn after the company was unable to agree with the FDA on post-marketing studies.

Gursel Aktan, head of global clinical development at Merck Research Laboratories, said the results “reinforce our research efforts in earlier stages of disease, where there is a greater potential for better outcomes.”

Meanwhile, Merck is also hoping to expand the label for Keytruda as a first-line therapy for metastatic cervical cancer to include patients regardless of the PD-L1 expression status of their tumours.

New data from the KEYNOTE-826 trial presented at this year’s ASCO congress showed that when Keytruda was added to first-line chemo it cut the risk of death by 37% in an all-comer patient population.

Cervical cancer is one of the most common tumour types in women, with 14,500 new cases diagnosed every year in the US and 4,300 deaths.