Higher Complete Pathologic Regression Rate With Neoadjuvant Docetaxel- vs Epirubicin-Based Triplets in Gastric/Gastroesophageal Junction Cancer
In the phase II portion of a German phase II/III trial (FLOT4) reported in The Lancet Oncology, Al-Batran et al found that preoperative docetaxel-based vs anthracycline-based triplet therapy produced a higher complete histopathologic regression rate in patients with resectable gastric or gastroesophageal junction cancer who had clinical stage ≥ cT2 or node-positive (cN+) disease.
Study Details
The open-label study was an investigator-initiated trial performed at 28 German oncology centers. In the phase II portion, between August 2010 and August 2012, 300 patients were randomized to receive 3 preoperative and 3 postoperative 3-week cycles of epirubicin at 50 mg/m² on day 1, cisplatin at 60 mg/m² on day 1, and either fluorouracil at 200 mg/m² as continuous intravenous infusion or oral capecitabine at 1,250 mg/m² on days 1 to 21 (ECF/ECX group, n = 152) or 4 preoperative and 4 postoperative 2-week cycles of docetaxel at 50 mg/m², oxaliplatin at 85 mg/m², leucovorin at 200 mg/m², and fluorouracil at 2,600 mg/m² as a 24-hour infusion, all on day 1 (FLOT group, n = 148).
Of these, 265 patients, including 137 in the ECF/ECX group and 128 in the FLOT group, were assessable on a modified intention-to-treat basis. The primary endpoint was pathologic complete regression (tumor regression grade TRG1a) in the modified intention-to-treat population. The study (including the phase III part) has completed enrollment, and follow-up is ongoing; the current report is an interim analysis.
Higher Complete Pathologic Regression Rate
Overall, 119 (93%) of 128 patients in the FLOT group and 126 (92%) of 137 in the ECF/ECX group received all planned preoperative treatment cycles. Pathologic complete regression was observed in 16% (95% confidence interval [CI] = 10%–23%) of the FLOT group vs 6% (95% CI = 3%–11%) of the ECF/ECX group (P = .02).
Adverse Events
At least 1 serious adverse event involving a perioperative medical or surgical complication occurred in 30 (25%) of 119 patients in the FLOT group and 44 (40%) of 111 patients in the ECF/ECX group. The most common nonsurgical grade 3 or 4 adverse events were neutropenia (52% of FLOT group vs 38% of ECF/ECX group), leukopenia (28% vs 20%), nausea (9% vs 17%), infection (12% vs12%), fatigue (9% vs 14%), and vomiting (3% vs 10%).
The investigators concluded: “Perioperative FLOT was active and feasible to administer, and might represent an option for patients with locally advanced, resectable gastric or gastro-esophageal junction adenocarcinoma.”
Salah-Eddin Al-Batran, MD, of UCT University Cancer Center, Frankfurt, is the corresponding author for The Lancet Oncology article.
The investigators reported that there was no funding for the study.
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