GI cancer

Failed bowel cancer trial finds silver lining

Study co-researcher Professor John Zalcberg of Monash University, Melbourne

A trial exploring the use of a cancer stem cell inhibitor in advanced bowel cancer that terminated early due to futility may have uncovered a potential new treatment target.

The double blind randomised phase 3 trial involved 282 patients with advanced bowel cancer recruited from 68 global cancer centres, including Australia. Patients were required to have a good Eastern Cooperative Oncology Group performance status (ECOG 0-1) and to have failed prior treatments.

Patients were randomised to napabucasin (n=138) 480mg or placebo (n=144) every 12 hours.

The study published in The Lancet Gastroenterology & Hepatology found no overall or progression free survival benefit with the pSTAT3 inhibitor compared with placebo.

Median overall survival was 4.4 months in the napabucasin group and 4.8 months in the placebo group (HR 1.1395% CI 0.88-1.46, p=0.34).

Patients taking the active drug were more likely to experience diarrhoea, nausea and anorexia compared to patients taking placebo.

However among patients who received placebo, positivity for pSTAT3 was a significant poor prognostic factor, found the research team that included Derek Jonker from the Royal Hobart Hospital in Tasmania.

Median overall survival was 3 months for patients with pSTAT3 positive tumours compared to 4.9 months for patients with pSTAT3 negative tumours (HR 2.3 p<0.0001).

Among patients with pSTAT3-positive tumours, median overall survival was 5·1 months with napabucasin versus 3 months with placebo (HR 0·41, 0·23–0·73, p=0·0025).

Whereas, in patients with pSTAT3-negative tumours, napabucasin was associated with reduced overall survival (median 4 months for pSTAT3-negative patients vs 4·9 months for pSTAT3-negative patients; HR 1·38, p=0·033).

“Patients who expressed pSTAT3 in archival tumour and stromal tissue may have an overall survival benefit when treated with the drug [napabucasin]… our findings suggest this pathway could be targeted to treat patients with colorectal cancer,” they wrote.

As such, further investigation of napabucasin as monotherapy in advanced colorectal cancer was warranted, they added.

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