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
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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. / Hofheinz, Ralf-Dieter; Merx, Kirsten; Haag, Georg M; Springfeld, Christoph; Ettrich, Thomas; Borchert, Kersten; Kretzschmar, Albrecht; Teschendorf, Christian; Siegler, Gabriele; Ebert, Matthias P; Goekkurt, Eray; Mahlberg, Rolf; Homann, Nils; Pink, Daniel; Bechstein, Wolf; Reichardt, Peter; Flach, Hagen; Gaiser, Timo; Battmann, Achim; Oduncu, Fuat S; Loose, Maria; Sookthai, Disorn; Pauligk, Claudia; Göetze, Thorsten O; Al-Batran, Salah-Eddin.
in: J CLIN ONCOL, Jahrgang 40, Nr. 32, 10.11.2022, S. 3750-3761.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - 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
AU - Hofheinz, Ralf-Dieter
AU - Merx, Kirsten
AU - Haag, Georg M
AU - Springfeld, Christoph
AU - Ettrich, Thomas
AU - Borchert, Kersten
AU - Kretzschmar, Albrecht
AU - Teschendorf, Christian
AU - Siegler, Gabriele
AU - Ebert, Matthias P
AU - Goekkurt, Eray
AU - Mahlberg, Rolf
AU - Homann, Nils
AU - Pink, Daniel
AU - Bechstein, Wolf
AU - Reichardt, Peter
AU - Flach, Hagen
AU - Gaiser, Timo
AU - Battmann, Achim
AU - Oduncu, Fuat S
AU - Loose, Maria
AU - Sookthai, Disorn
AU - Pauligk, Claudia
AU - Göetze, Thorsten O
AU - Al-Batran, Salah-Eddin
PY - 2022/11/10
Y1 - 2022/11/10
N2 - 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.
AB - 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.
KW - Humans
KW - Female
KW - Leucovorin/therapeutic use
KW - Docetaxel/adverse effects
KW - Oxaliplatin/therapeutic use
KW - Stomach Neoplasms/drug therapy
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Receptor, ErbB-2/metabolism
KW - Trastuzumab/adverse effects
KW - Adenocarcinoma/drug therapy
KW - Fluorouracil/adverse effects
KW - Leukopenia/etiology
KW - Diarrhea/etiology
KW - Breast Neoplasms/drug therapy
U2 - 10.1200/JCO.22.00380
DO - 10.1200/JCO.22.00380
M3 - SCORING: Journal article
C2 - 35709415
VL - 40
SP - 3750
EP - 3761
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
IS - 32
ER -