FLOT ‘New Standard Of Care’ For Resectable Oesophago-Gastric Cancer

Sensitivity and subgroup analyses substantiate superiority of perioperative docetaxel, oxaliplatin and 5-fluorouracil/leucovorin for operable gastric and gastro-oesophageal junction adenocarcinoma

medwireNews: Phase III study findings add support for the use of perioperative docetaxel, oxaliplatin and 5-fluorouracil/leucovorin (FLOT) in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma.

Reporting at the ESMO 2017 Congress in Madrid, Spain, the trial investigators shared multivariate, subgroup and sensitivity results for the FLOT4-AIO trial showing superior outcomes for the 356 FLOT-treated patients compared with the 360 patients who were given a perioperative regimen of epirubicin, cisplatin and infused 5-fluorouracil (ECF), the current standard of care.

Presenting author Salah-Eddin Al-Batran, from the University Cancer Center Frankfurt in Germany, explained that, as previously reported at the ASCO 2017 meeting, the triplet regimen led to a significantly higher rate of curative resection than did ECF (94 vs 87%), followed by significantly longer progression-free survival (PFS; 30 vs 18 months, hazard ratio [HR]=0.75) and overall survival (OS; 50 vs 35 months, HR=0.77).

The latest data for the predefined sensitivity analyses gave a “highly significant” HR of 0.76 for OS in favour of FLOT in the per-protocol population, and multivariate analysis confirmed a significant HR of 0.74 for OS with FLOT after adjusting for factors such as ECOG performance status, age, tumour location and lymph node status.

In addition, post-hoc analysis demonstrated that FLOT4 was associated with a PFS gain in patients whether or not they underwent tumour resection, indicating that the benefit was not just the consequence of tumour shrinkage allowing a better surgical outcome, Salah-Eddin Al-Batran explained.

Subgroup analysis of prognostic factors showed that patients with gastro-oesophageal junction tumours had worse OS than those with gastric cancer, as did patients with cT3/4 versus those with cT1/2 tumours, node-positive patients versus their node-negative counterparts, and those with grade 3 or 2–3 disease versus those with grade 1/2.

Moreover, Salah-Eddin Al-Batran reported that FLOT treatment resulted in a better outcome than ECF for patients regardless of stage, nodal status, the presence or absence of Barrett mucosa, and whether the patient had diffuse or nondiffuse type disease.

The study also showed that patients with signet cell component disease, defined as at least one signet cell, had a significantly lower OS than those without.

“However, these patients derived benefit from FLOT versus ECF”, the investigator said, adding that the effect of FLOT was “pronounced” compared with the difference achieved by FLOT versus ECF for patients without signet cell tumours. This finding may change how we deal with this tumour type, he emphasized.

“The results confirm that FLOT is [a] new standard of care in perioperative treatment of patients with adenocarcinoma of the stomach or gastroesophageal junction”, Salah-Eddin Al-Batran concluded.

“The results support the concept of perioperative therapy in some subgroups that [have] been debateable”, he said, such as the elderly, those with signet cell cancer or Barrett mucosa, and those with cT2 or cN-positive disease.

Reference

Al-Batran S-E, Pauligk C, Homann N, et al. LBA27_PR – Docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) for resectable esophagogastric cancer: updated results from the multicenter, randomized phase 3 FLOT4-AIO trial (German Gastric Group at AIO). ESMO 2017 Congress; Madrid, Spain: 8–12 September.

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