No Gastric Cancer Survival Benefit in CRITICS Trial

Liam Davenport

July 05, 2016

BARCELONA, Spain — For patients with gastric cancer, the question of whether to intensify postoperative treatment with chemoradiotherapy has been answered by a large European study, the CRITICS trial, which found no extra survival benefit from postoperative radiotherapy added onto chemotherapy alone.

Lead author Marcel Verheij, MD, PhD, from the Netherlands Cancer Institute, Amsterdam, told delegates here at the 18th World Congress on Gastrointestinal Cancer (WCGC) that for gastric cancer patients treated with preoperative chemotherapy followed by adequate surgery, the postoperative treatment boost was similar in both arms of the study. The 5-year survival rate was around 40% both after postoperative chemotherapy and after postoperative chemoradiation.

Commenting on the study, Dirk Arnold, MD, PhD, from the Instituto CUF de Oncologia in Lisbon, Portugal, commented in a release that "it is well known that only a limited number patients are good candidates for any postoperative treatment following gastrectomy" and that, as such, any intensification of postoperative treatment "may not be the right strategy."

Although some subgroups of patients did benefit from postoperative chemoradiation, Dr Arnold said that overall, the findings should prompt "an intensification of the preoperative treatment, and already other trials are evaluating different approaches, including chemoradiation...compared to standard chemotherapy alone."

Discussing the use of adjuvant and neoadjuvant therapy in gastric cancer after the presentation, William H. Allum, MD, from the Royal Marsden NHS Foundation Trust in London, the United Kingdom, said that there is a "potential role for chemoradiotherapy in surgical procedures."

However, the issue with previous trials has been that surgery was not standardized, "and the criticism has always been that chemoradiotherapy postoperatively made up for less than what would be accepted now as appropriate surgery."

Dr Allum noted that in the CRITICS trial, the surgery was "more standardized," and that this trial shows that "chemoradiotherapy across the whole set of patients is not having an effect on what can be considered pretty optimal surgery in current parlance.

"It remains to be seen what the subgroup analysis shows with regard to lymph node–positive patients," he added.

Results From the CRITICS Trial

The CRITICS study was a randomized phase 3 trial in which patients with stage Ib-IVa resectable gastric cancer who had already been treated with preoperative chemotherapy and adequate surgery were then randomly assigned to receive either chemoradiotherapy or chemotherapy alone.

"The rationale of postoperative chemoradiotherapy after preoperative chemotherapy is to combine systemic and locoregional treatments to reduce the risk of recurrent disease and improve outcomes," Dr Verheij explained. He noted that gastric cancer commonly presents at advanced stages, that long-term survival is poor, and that up to 80% of patients experience local recurrence.

The preoperative chemotherapy consisted of three courses of epirubicin, cisplatin/oxaliplatin, and capecitabine (EEC/EOC) before extended (D2) lymph-node dissection gastric resection. This was followed by three courses of EEC/EOC or chemoradiotherapy, consisting of 45 Gy in 25 fractions plus weekly cisplatin and daily capecitabine.

The researchers randomly assigned a total of 788 patients from the Netherlands, Sweden, and Denmark to postoperative chemotherapy (n = 393) or chemoradiotherapy (n = 395) between 2007 and 2015. The two patient groups were well balanced; the overall median age of the patients was 62 years.

Although 94% of patients in the postoperative chemotherapy arm and 93% in the chemoradiotherapy arm underwent surgery (with surgery being curative in 80% and 84% of patients, respectively), only 61% and 63%, respectively, started postoperative treatment, and just 47% and 52%, respectively, completed it.

The most common reasons why postoperative chemotherapy or chemoradiotherapy was not employed was patient refusal, followed by the presence of progressive disease, toxicity to preoperative chemotherapy, and postoperative complications.

There were few differences in rates of toxicity following postoperative treatment, although patients who received chemotherapy were significantly more likely than those given chemoradiotherapy to have grade 3 or 4 neutropenia, at 34% vs 4% (P < .001). The other most common grade 3 and 4 toxicities were anorexia, nausea, and fatigue.

After a median follow-up of 4.2 years, there were 406 deaths. The median survival for patients receiving chemotherapy was 3.5 years vs 3.3 years with chemoradiotherapy, yielding a 5-year overall survival rate of 40.8% for chemotherapy vs 40.9% for chemoradiotherapy (P = .99).

Median progression-free survival in the chemotherapy group was 2.3 years vs 2.5 years in the chemoradiotherapy group; 5-year progression-free survival was 38.5% and 39.5%, respectively (P = .99).

In conclusion, Dr Verheij said that the expected treatment difference in overall survival has not been observed. He added that the 5-year overall and median survival rates reported in this study were comparable with those of other studies in Western countries.

"Based on these currently available data, we cannot give advice on the preferred adjuvant strategy," he said. "However, ongoing subgroup analyses may identify treatment benefits in specific subgroups of patients.

"Because less than 50% of patients were able to complete full treatment protocols, we think that more emphasis should be put on the preoperative phase of treatment," he added.

The authors have disclosed no relevant financial relationships.

18th World Congress on Gastrointestinal Cancer (WCGC): Abstract LBA-002. Presented June 29, 2016.


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