“The rationale of postoperative chemoradiotherapy after preoperative chemotherapy is to combine systemic and loco-regional treatments to reduce the risk of recurrent disease and improve outcomes,” said the study’s (1) principal investigator Professor Marcel Verheij from the Netherlands Cancer Institute.
Peri-operative (pre- and post-operative) chemotherapy are the current standard of treatment for gastric cancer, but previous studies have suggested that post-operative chemoradiotherapy alone may improve outcomes to a similar extent.
In this phase III study, 788 patients with stage Ib-IVa resectable gastric cancer were randomized upfront and were all given pre-operative chemotherapy consisting of three courses of epirubicin, a platinum compound (cisplatin or oxaliplatin) and capecitabine.
After surgery, patients randomized to the ‘standard’ arm continued with another three courses of the same chemotherapy regime, while the others received chemoradiotherapy involving 45 Gy in 25 fractions combined with weekly cisplatin and daily capecitabine.
Researchers found a five-year survival rate of 40.8% in the chemotherapy arm, and 40.9% in the chemoradiotherapy arm, showing equivalent efficiency between the two treatment options.
There was a higher incidence of grade 3 or higher hematological adverse events in the chemotherapy arm (44% v 34%) but a higher incidence of gastrointestinal adverse events in the chemoradiotherapy arm (42% v 37%).
While the surgical quality was very high in the study, researchers noted that a significant number of patients did not start or complete the full course of either chemotherapy or chemoradiotherapy; 52% in the chemotherapy arm, and 47% in the chemoradiotherapy arm.
Professor Verheij said the team had anticipated a better outcome from the post-operative chemoradiotherapy arm compared to the peri-operative chemotherapy arm, but said subgroup analyses may identify specific patient populations who will benefit from either approach.
Commenting on the findings, Dr Dirk Arnold, from the Instituto CUF de Oncologia in Lisbon, Portugal, said, “it is well known that only a limited number patients are good candidates for any post-operative treatment following gastrectomy, so any post-operative treatment intensification may not be the right strategy.”
“Despite the identification of subgroups benefitting from this approach with postoperative chemoradiation, the strategy should prompt into an intensification of the pre-operative treatment, and already other trials are evaluating different approaches, including chemoradiation in this setting, compared to standard chemotherapy alone,” Dr Arnold said.