Bevacizumab Ruled Out As Adjuvant Therapy for Resectable Gastro-oesophageal Cancer

The addition of bevacizumab to epirubicin, cisplatin and capecitabine peri-operative chemotherapy did not improve overall survival or other outcomes for patients with gastro-oesophageal cancer

medwireNews: Negative results from the ST03 trial of bevacizumab plus peri-operative chemotherapy have been published in The Lancet Oncology, ruling out a role for the angiogenesis inhibitor in the treatment of operable gastro-oesophageal cancer.

“The results of this trial do not provide any evidence for the use of bevacizumab in combination with peri-operative epir[u]bicin, cisplatin, and capecitabine chemotherapy for patients with resectable gastric, oesophagogastric junction, or lower oesophageal adenocarcinoma”, say David Cunningham, from the Royal Marsden NHS Foundation Trust in Sutton, UK and co-authors.

 And they caution: “Bevacizumab might also be associated with impaired wound healing.”

Overall survival was comparable in the 530 patients who received bevacizumab plus chemotherapy and the 533 patients given chemotherapy alone, with 3-year rates of 48.1% and 50.3%, respectively.

There was no evidence of better disease-free survival or progression-free survival with bevacizumab treatment. Nor did combined treatment lead to a better rate of RECIST and pathological tumour responses or a greater likelihood of achieving a complete surgical resection.

Increased neutropenia in the combined treatment arm was the only adverse event to affect more than 10% of patients but this side effect and other toxicities were comparable between the chemotherapy and chemotherapy plus bevacizumab groups,

But patients treated with bevacizumab plus chemotherapy had a higher rate of wound healing complications than those given chemotherapy alone, at 12% versus 7%.

For patients who underwent oesophagogastrectomy, postoperative anastomotic leaks were more than twice as common in the bevacizumab-treated patients, affecting 24% of 220 patients versus 10% of 233 patients given chemotherapy only.

“[T]herefore, recruitment of patients with lower oesophageal or junctional tumours planned for an oesophagogastric resection was stopped towards the end of the trial”, the investigators say.

In all, there were 69 serious adverse events, including anastomotic leaks, in the chemotherapy plus bevacizumab group versus 30 in the chemotherapy only arm, with 53 and 42 infections with a normal neutrophil count reported, respectively.

Describing the findings in an accompanying comment as “a big disappointment”, Florian Lordick, from the University Cancer Center Leipzig in Germany, suggests that “adoptive study designs could prevent large negative phase 3 trials in the future.”

“Additionally, treatment stratification according to tumour biology, individual response, and risk features might increase the chances of new interventions being successful”, he says.

“Ultimately, despite the negative outcome of this trial, we hope that further developments in future studies will lead to more effective drugs for treatment of oesophageal and gastric cancer appearing on the horizon.”

References

Cunningham D, Stenning SP, Smyth EC, et al. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2–3 trial. Lancet Oncol; Advance online publication 2 February 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30043-8 

Lordick F. Anti-angiogenesis: disappointment in localised oesophagogastric cancer. Lancet Oncol; Advance online publication 2 February 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30029-3 

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