MSD's Keytruda doubles PFS in bowel cancer subset

MSD's immunotherapy Keytruda (pembrolizumab) more than doubled progression free survival in patients with a specific subtype of advanced bowel cancer, when compared with chemotherapy, a large trial involving UCL and University College London Hospitals NHS Foundation Trust (UCLH) has found.

Interim analysis of the data, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, showed that progression free survival in patients given the drug was 16.5 months (on average), compared with 8.2 months for given chemotherapy.

Furthermore, 11% of patients treated with Keytruda had a complete response, while in almost half of patients given the drug (48.3%) their disease had not progressed after two years compared to just 18.6% in the chemotherapy arm.

“This is the first randomised controlled study to show that first-line immunotherapy is significantly better than chemotherapy at shrinking metastatic bowel cancers with these specific DNA mutations, and delaying the time it takes for the cancer to progress,” noted the trial’s UK chief investigator, Dr Kai-Keen Shiu, Honorary Associate Professor in Oncology at UCL Cancer Institute and consultant Medical Oncologist at UCLH.

“Whilst only around 5% of advanced bowel cancer patients have these genetic mutations, they usually have a worse prognosis, and less response to chemotherapy and other targeted agents. The results from this trial really are game-changing and will almost certainly result in a paradigm shift in our current clinical practice.”

The KEYNOTE-177 trial, funded by MSD, recruited 307 patients with metastatic bowel cancer, who had specific DNA mutations known as microsatellite instability high (MSI-H) or mismatch repair deficiency (dMMR).

These result in cells being unable to repair themselves correctly if damaged, and when this happens, errors in the DNA can accumulate and cause cancer.

The trial recruited patients from 23 countries who were put into two equally sized groups. In one arm patients received pembrolizumab every three weeks for up to 35 cycles of treatment (up to approximately two years), while in the other patients were treated with standard chemotherapy combinations with cancer targeting drugs bevacizumab or cetuximab (the chemotherapy arm) every two weeks.

For patients treated with Keytruda, progression-free survival was found to be 55.3% at 12 months and 48.3% at 24 months, compared to 37.3% and 18.6% respectively, for those on chemotherapy.

On average, patients given Keytruda had a progression free survival of 16.5 months, compared with 8.2 months of chemotherapy – an improvement of 8.3 months, while 32.7% had a partial response compared to 29.2% on chemotherapy.

Also of note, severe treatment-related adverse events were also less common with Keytruda at 22% versus 66% for chemotherapy.

“It is very encouraging that the side effects of pembrolizumab are significantly less than with chemotherapy, so not only the quantity but also the quality of life of these patients is better on immunotherapy,” noted Dr Shiu added.

“Some of my trial patients had a complete response to this therapy, are very well and have now been in remission for more than three years.”

Lead author Professor Thierry André, of the University of Sorbonne, France, said the study demonstrates the "huge benefit" of first line treatment with pembrolizumab and that this "should be the new standard of care.”