Showing papers by "Nils Homann published in 2022"

FLOT Versus FLOT/Trastuzumab/Pertuzumab Perioperative Therapy of Human Epidermal Growth Factor Receptor 2–Positive Resectable Esophagogastric Adenocarcinoma: A Randomized Phase II Trial of the AIO EGA Study Group

Abstract: PURPOSE High pathologic complete response (pCR) rates and comparably good survival data were seen in a phase II trial combining perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy with trastuzumab for resectable, esophagogastric adenocarcinoma (EGA). The current trial evaluates the addition of trastuzumab and pertuzumab to FLOT as perioperative treatment for human epidermal growth factor receptor 2–positive resectable EGA. METHODS In this multicenter, randomized phase II/III trial, patients with human epidermal growth factor receptor 2–positive, resectable EGA (≥ clinical tumor 2 or clinical nodal–positive) were assigned to four pre- and postoperative cycles of either FLOT alone (arm A) or combined with trastuzumab and pertuzumab, followed by nine cycles of trastuzumab/pertuzumab (arm B). The primary end point for the phase II part was the rate of pCR. RESULTS The trial was closed prematurely, without transition into phase III, after results of the JACOB trial were reported. Eighty-one patients were randomly assigned (A: 41/B: 40) during the phase II part. The pCR rate was significantly improved with the trastuzumab/pertuzumab treatment (A: 12%/B: 35%; P = .02). Similarly, the rate of pathologic lymph node negativity was higher with trastuzumab/pertuzumab (A: 39%/B: 68%), whereas the R0 resection rate (A: 90%/B: 93%) and surgical morbidity (A: 43%/B: 44%) were comparable. Moreover, the inhouse mortality was equal in both arms (overall 2.5%). The median disease-free survival was 26 months in arm A and not yet reached in arm B (hazard ratio, 0.58; P = .14). After a median follow-up of 22 months, the median overall survival was not yet reached (hazard ratio, 0.56; P = .24). Disease-free survival and overall survival rates at 24 months were 54% (95% CI, 38 to 71) and 77% (95% CI, 63 to 90) in arm A and 70% (95% CI, 55 to 85) and 84% (95% CI, 72 to 96) in arm B, respectively. More ≥ grade 3 adverse events were reported with trastuzumab/pertuzumab, especially diarrhea (A: 5%/B: 41%) and leukopenia (A: 13%/B: 23%). CONCLUSION The addition of trastuzumab/pertuzumab to perioperative FLOT significantly improved pCR and nodal negativity rates at the price of higher rates of diarrhea and leukopenia.

Perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma (RAMSES/FLOT7) with high rate of signet cell component: Final results of the multicenter, randomized phase II/III trial of the German AIO and Italian GOIM.

Abstract: 4042 Background: Periop. FLOT has become SOC for resectable, esophagogastric adenocarcinoma. However, patient’s outcome is still poor. This trial evaluates the addition of the VEGF-R2 inhibitor ramucirumab (RAM) to FLOT for resectable patients (pts). Methods: This is a prospective, international, randomized, investigator-initiated phase II/III trial. Pts with resectable, Her2-negative, adenocarcinoma of the stomach and GEJ type II and III (≥ cT2 or cN+) were enrolled. Pts were randomized to 4 pre-and post-operative cycles of FLOT (docetaxel 50 mg/m²; oxaliplatin 85 mg/m²; leucovorin 200 mg/m²; 5-FU 2600 mg/m², q2w) alone (Arm A) or the same regimen with RAM 8mg/kg q2w, followed by 16 cycles RAM (Arm B, FLOT-RAM). Important endpoints of phase II (exploratory) were major pathological (complete and nearly complete) response, centrally assessed acc. to Becker criteria, R0-resection rate, overall survival (OS), disease-free survival (DFS) and safety. GEJ type I tumors and pts requiring trans-thoracic esophagectomy were excluded for safety reasons during the conduct of the study. Results: In total, 152 pts were analyzed within the intention to treat population. Baseline characteristics were similar between arms (male, 70%; median age, 60y; cT3/T4, 82%; cN+, 77%; GEJ, 45%). The rate of cancers with signet-ring cell component was at 45%. The FLOT-RAM arm included more unfavorable pts with T4 (8% vs. 5%), impaired ECOG PS of 1 (32% vs. 20%), and concomitant disease (86% vs. 76%). 92% of pts with FLOT as well as with FLOT-RAM completed the 4 pre- cycles. R0-resection could be achieved in 82% of pts with FLOT and 96% of pts with FLOT-RAM (p = 0.0093). The rate of major path response was similar in both arms and was 29% for FLOT and 26% for FLOT-RAM. Median DFS was slightly improved in pts with FLOT-RAM (32 months vs. 21 months), while median OS was similar in both treatment arms (FLOT 45 months, FLOT-RAM 46 months). Surgical morbidity was observed in 32% of pts with FLOT and 41% of pts with FLOT-RAM. Mortality at 60 days after surgery was 4.1% with FLOT and 2.8% with FLOT-RAM. There were bit more G≥3 adverse events with FLOT-RAM (76% vs. 92%). Conclusions: In this phase II trial, the addition of ramucirumab to perioperative FLOT significantly improved R0-resection rates and slightly prolonged DFS without an impact on path response or overall survival. FLOT-RAM is feasible and safe, when type I tumors are excluded. Clinical trial information: NCT02661971.