No role for bevacizumab in localized esophagogastric cancer
medwireNews: Phase III trial results indicate that the addition of bevacizumab to peri-operative chemotherapy does not improve the outcomes of patients with resectable esophagogastric adenocarcinoma and may even be associated with impaired wound healing.
Just under half (48.1%) of the 530 participants with operable gastric, Siewert type I–III esophagogastric junction, or lower esophageal adenocarcinoma who received bevacizumab alongside three cycles of chemotherapy with epirubicin, cisplatin, and capecitabine before and after surgery were alive at 3 years.
This was not significantly different from the 50.1% rate observed for the 533 given peri-operative chemotherapy alone (hazard ratio of 1.08 favoring chemotherapy alone).
Disease-free and progression-free survival were similarly comparable between the groups, as were the proportions of patients achieving a response according to RECIST or a pathologic tumor response. And contrary to the researchers’ hypothesis, bevacizumab addition prior to surgery did not translate into an increased rate of R0 resections either.
They write in The Lancet Oncology: “The results of this trial suggest that there is unlikely to be a role for bevacizumab in the treatment of localised, operable oesophagogastric cancer.”
Indeed, the team believes there is potential cause for concern, with higher rates of impaired wound healing in the bevacizumab than the chemotherapy alone group, at 12% versus 7%.
Furthermore, in the subgroup of participants who underwent esophagogastrectomy, postoperative anastomotic leaks were more common among bevacizumab-treated patients than their counterparts given chemotherapy alone, at 24% of 220 and 10% of 233, respectively.
As a result, “recruitment of patients with lower oesophageal or junctional tumours planned for an oesophagogastric resection was stopped towards the end of the trial,” David Cunningham (Royal Marsden NHS Foundation Trust, Sutton, UK) and fellow ST03 investigators report.
Observing that the findings are “not practice changing,” they conclude: “Ongoing exploration of novel therapies in order to improve outcomes for oesophagogastric cancer patients is warranted.”
In a related comment, Florian Lordick (University Cancer Center Leipzig, Germany) describes the results as “a big disappointment” and notes: “[O]nce more, as has been previously reported in several trials of colon, breast, and lung cancer, the efficacy of anti-angiogenic drugs as reported in stage IV tumours did not translate to a benefit in early-stage disease.”
He says that “[a]doptive study designs could prevent large negative phase 3 trials in the future” and “treatment stratification according to tumour biology, individual response, and risk features might increase the chances of new interventions being successful.”
Lordick concludes: “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.”
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