Advanced bowel cancer trial results from FOCUS4: A promising new drug, and treatment breaks

20 Sep 2021

A promising new drug

A new drug has shown promise in delaying the time to the disease getting worse in some bowel cancer patients whose cancer has spread elsewhere in the body. This is according to results published at the weekend in the Journal of Clinical Oncology.

For the 44 patients that took the drug, called adavosertib, it took longer for their cancer to get worse. This was compared to 25 patients who were monitored instead of receiving the drug. The drug was more effective in the 31 patients whose cancer was located in the left sided part of the bowel’.

These results are from the FOCUS4-C part of the FOCUS4 trial. More than 1400 patients took part in FOCUS4 which looked to find the most effective treatments for patients with advanced bowel cancer that had different chemical properties or genetic mutations.

Patients who joined the trial were started on a course of chemotherapy for up to 16 weeks. During this time a piece of their tumour was tested to find out more about the chemical make-up of the tumour.

Patients were assessed after the 16 weeks of chemotherapy to see how the tumour was responding to standard treatment. If the cancer had shrunk or at least not grown, patients were eligible to enter a clinical trial testing a particular treatment in their sub-type of cancer.

Participants in the FOCUS4-C arm had tumours with two common mutations, RAS and TP53. The researchers predicted that these tumours would be more sensitive to adavosertib.

These early results pave the way for a larger trial to see whether the drug improves survival for patients compared to standard treatment.

Lead author Dr Jenny Seligmann (University of Leeds) said: “These results show promising signs that adavosertib may be effective in delaying re-growth of bowel cancer in some patients and is well tolerated. The findings are particularly encouraging as the subset of patients involved represent a third of all bowel cancer patients and, while other patients have treatments developed specifically for their tumour types, this group currently has very limited treatment options.”

Bowel cancer is the fourth most common cancer in the UK and the second biggest cancer killer. Over 42,000 people are diagnosed with bowel cancer every year in the UK.

Co-author Professor Louise Brown (MRC Clinical Trials Unit at UCL) said: “Our UK-wide trial is the first in the world to investigate potential treatments for bowel cancer by stratifying patient groups according to the chemical make-up of their tumours. This allowed us to test several new approaches at the same time. The results for the adavosertib arm of the trial are potentially important and represent a glimmer of hope for patients in this group.”

Treatment breaks as a sound alternative to maintenance therapy

Findings from another part of FOCUS4 (FOCUS4-N) show that patients can have a break from bowel cancer treatment, following chemotherapy, without it affecting how long they live.

Patients in the FOCUS4-N part of the trial could join the trial regardless of the chemical make-up of their tumour. After finishing chemotherapy, they were randomised to receive either a maintenance treatment called capecitabine, or a treatment break.

Maintenance treatment delayed re-growth of the tumour when compared with a treatment break. However, although the maintenance therapy increased the time until disease got worse, it did not help patients live any longer.

Some patients taking the maintenance therapy experienced side effects such as tiredness, diarrhoea, and hand-foot syndrome (redness, swelling and pain in the hands and feet).
Lead author Professor Richard Adams (Cardiff University) said: “the findings will help to inform discussions between patients and clinicians about treatment options at the end of four months of therapy, whether to stay on oral chemotherapy long-term or have a complete break in treatment, giving patients better control of their cancer management.”

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