Phase III trial finds no significant difference in overall survival
Barcelona-Lugano, June 30, 2016 – Post-operative treatment intensification with chemoradiotherapy does not achieve better outcomes when compared to post-operative chemotherapy in patients with gastric cancer who have already undergone pre-operative chemotherapy, according to phase III data presented at the ESMO 18th World Congress of Gastrointestinal Cancer in Barcelona, Spain.
“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.
Notes to Editors
Information contained in this press release was provided by the abstracts authors and reflects the content of the studies. It does not necessarily express ESMO’s point of view.
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A multicenter randomized phase III trial of neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy in resectable gastric cancer: First results from the CRITICS study.
Marcel Verheij,1 Annemieke Cats,1 Edwin PM Jansen,1 Nicole C.T. van Grieken,2 Neil K Aaronson,1 Henk Boot,1 Pehr A. Lind,3 Elma Meershoek – Klein Kranenbarg,4 Marianne Nordsmark,5 Hein Putter,4 Harm van Tinteren,1 Cornelis J. H. Van De Velde4
- Netherlands Cancer Institute
- VU University Medical Center
- Karolinska University Hospital
- Leiden University Medical Center
- Århus University Hospital
Background: The mainstay of potentially curative treatment of gastric cancer is radical surgical resection. Because most patients in the Western world present with advanced stages long-term survival remains poor at about 25%, with local recurrences as part of treatment failure in up to 80% of cases. Evidence-based strategies aimed at improving outcome include adequate surgery, post-operative chemoradiotherapy (CRT) and peri-operative chemotherapy (CT). The current randomized phase III CRITICS-study (NCT00407186) investigated whether chemoradiotherapy after pre-operative chemotherapy and adequate (D2) surgery leads to improved overall survival (OS) in comparison with post-operative chemotherapy. Furthermore, toxicity of both treatment regimens was explored.
Methods: Patients with stage Ib-IVa resectable gastric cancer were randomized after diagnosis. Pre-operative CT was prescribed in both arms and consisted of 3 courses of epirubicin, cisplatin/oxaliplatin and capecitabine (ECC/EOC). After gastric cancer resection, patients received another 3 courses of ECC/EOC or CRT (45 Gy in 25 fractions combined with weekly cisplatin and daily capecitabine). Primary endpoint is OS; secondary endpoints are: progression free survival, toxicity profile and quality of life.
Results: Between January 2007 and April 2015, 788 patients from The Netherlands, Sweden and Denmark were randomized (393 CT; 395 CRT). Baseline characteristics were well balanced with 67% males and a median age of 62 years. 83% completed 3 cycles before surgery. In the CT arm 47% and in the CRT arm 52% completed treatment according to protocol. After a median follow-up of 4.2 years, 406 patients have died. The 5-year overall survival is 40.8% for CT and 40.9% for CRT (p=0.99). Toxicity was mainly hematological (grade III or higher: 44% vs 34%; p=0.01) and gastrointestinal (grade III or higher: 37% vs 42%; p=0.14) for CT and CRT, respectively.
Conclusion: No significant difference in overall survival was found between postoperative chemotherapy and chemoradiotherapy.
- LBA-02: A multicenter randomized phase III trial of neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy in resectable gastric cancer: First results from the CRITICS study will be presented by Marcel Verheij during Session VI: Gastric Cancer on Thursday, 30 June 2016, 11:30 (CEST).
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