ESMO Commentary: TOPGEAR results set to unify global treatment of gastric cancer

VIENNA, Austria – Gastric cancer (GC) is one of the most aggressive oncologic diseases, with a 5 year median survival of 25%. Surgery remains the only curative option, although with a high recurrence rate. “Different strategies have been proposed, including pre and post-operative chemo and chemo radiotherapy, to improve the outcome of these potentially curable patients,” said Professor Josep Tabernero, Head of the Medical Oncology Department at Vall d’Hebron University Hospital, Barcelona, Spain, member of the ESMO Executive Board. 

“While the benefit of chemo and radiotherapy in these patients is clear, the best sequence remains unclear,” he continued. “Pre-operative strategies play with the advantage of downstaging as well as potential micrometastasis eradication. In this sense, the TOPGEAR trial presented at the ECC2015 congress analyses whether giving the most complete strategy upfront translates into a survival benefit”.1

Still today peri-operative chemo radiotherapy is the standard of care in Europe, while post-operative chemo radiotherapy is the standard of care in North America, and post-operative chemotherapy is the preferred option in Asia.

The peri-operative choice has been based on the robust data from two phase III clinical trials, as Tabernero explains. “The MAGIC study randomised patients to receive peri-operative chemotherapy with epirubicin, cisplatin and 5-FU or not, and showed an improvement in the 5 year overall survival from 23% to 36% favouring those that did receive the peri-operative treatment. Furthermore, the FFCD 9703 study showed similar gain with peri-operative cisplatin and 5-FU, besides providing data of a high rate of R0 within the patients receiving chemotherapy.” 

Another phase III trial which was run in parallel, the EORTC 40954, could not demonstrate a statistically significant benefit in terms of survival, probably due to the poor recruitment. “However, it did show more small tumours and R0 resection in the patients within the peri-operative chemotherapy arm,” he continued.

Recent studies supported post-operative chemo radiotherapy as a standard of care. “In the INT 0116 study patients were randomised to receive or not treatment with 5-FU and radiotherapy after surgery,” Tabernero said. “It was a positive trial, showing a benefit in median survival, from 27 to 35 months. The results of the ACTS-GT and the CLASSIC trials also demonstrated a clear benefit of this strategy, by adding post-operative chemotherapy with S-1 and with capecitabine and oxaliplatin respectively.” 

Taking into account these results, and by considering firstly the downstaging power of chemotherapy and radiotherapy, and secondly the better tolerance of these treatments when administered before surgery, Tabernero said: “The TOPGEAR trial compares a control arm, with the MAGIC approach (epirubicin, cisplatin and 5-FU), with the experimental arm, which includes 2 cycles of the same chemotherapy regimen followed by chemo radiotherapy with 5-FU. After surgery, both groups receive the same chemotherapy treatment used in the MAGIC trial.”

Tabernero concluded: “Briefly, the safety profile shows very similar toxicity between the two arms. Therefore the experimental approach is completely feasible. Now we will have to wait for the efficacy in order to know the benefit of this more intense peri-operative strategy. By answering the question of the multimodality sequence, the results of this trial will help to unify the treatment of local and locally advanced gastric cancer around the world. The challenge then would be where to incorporate targeted strategies considering the heterogeneity of these tumours.” 


1Abstract presented at ECC 2015, held 25–29 September in Vienna, Austria:

2200: TOPGEAR: A randomized phase II/III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer. Interim results from an international, intergroup trial of the AGITG/TROG/NCIC CTG/EORTC. T. Leong, Australia. Tuesday 29th September 2015 – 08:30-10:50 Proffered Paper Session HALL C2

Information contained in this commentary was provided by the interviewee.