Higher Complete Pathologic Regression Rate With Neoadjuvant Docetaxel- vs Epirubicin-Based Triplets in Gastric/Gastroesophageal Junction Cancer

Key Points

  • Pathologic complete regression was observed in 16% of the FLOT group vs 6% of the ECF/ECX group.
  • Grade 3 or 4 neutropenia and leukopenia were more common in the FLOT group.

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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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