The addition of cediranib to treatment with cisplatin/gemcitabine did not improve progression-free survival in patients with advanced biliary tract cancer, according to the results of the phase II ABC-03 trial. However, improved objective response rate was observed in patients assigned to cediranib, according to Juan W. Valle, MD of the University of Manchester, who presented the results at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
As with a number of solid tumors, surgery is the only chance for long-term cure of biliary tract cancer; although, unfortunately, most patients present with inoperable advanced disease or relapse following potentially curative surgery.
According to Valle, previous research has shown that systemic chemotherapy can improve patient survival compared with best supportive care. However, to date, the role of second-line chemotherapy is not defined, and there is currently only a 5-year survival of about 5% to 10%.
In the ABC-03 trial, Valle and colleagues examined the effects of adding cediranib, a pan-VEGF receptor tyrosine kinase inhibitor, to traditional treatment with cisplatin/gemcitabine.
They performed a randomized phase II study of 124 chemotherapy-naive patients with advanced biliary tract cancer who were randomly assigned to cisplatin/gemcitabine with or without cediranib. The primary endpoint was progression-free survival.
Patients assigned cediranib had a significantly improved response rate compared with patients assigned placebo. Patients on cediranib had a response rate of 44%, including 3% with complete response, compared with a 19% response rate in patients receiving placebo (P = .0036). Patients receiving placebo were also more likely to progress (28% progressive disease vs 10% for cediranib).
However, no difference in progression-free survival was found between the two groups. The median progression-free survival for patients assigned cediranib was 8 months compared with 7.4 months for placebo (HR = 0.93; 95% CI, 0.65-1.35; P = .72).
“This is not incompatible with the previous findings of a higher response rate, which was seen at the 3-month time point, at which point the curves do appear to separate,” Valle said. “I would also like to highlight that the median time on cediranib was 4.6 months.”
There was also no statistically significant difference in overall survival between the two treatment arms (HR = 0.88; 95% CI, 0.58-1.27; P = .44).
“It has previously been known that higher levels of CA19-9 are associated with worse prognosis, and we were able to confirm that in this study with a statistically significant P value,” Valle said. “But we were also able to demonstrate that the same applies for CA125 and CEA.”
Looking at angiogenic markers, the researchers found that patients with high circulating VEGFR2 at baseline had a shorter overall survival than those with medium or low levels, and that this association was independent of treatment arm. Additionally, patients with low levels of baseline PDGF appeared to be disadvantaged by cediranib, but that patients with medium or high levels gain a survival advantage with cediranib. Dr. Valle said that both conclusions would need to be evaluated in a prospective manner.
There was no statistically significant difference between hematologic toxicities between the two arms. However, patients on cediranib had a significant increase in any nonhematologic adverse events, driven by an increase in hypertension (P = .05) and diarrhea (P = .05).