TY - JOUR
T1 - Perioperative FLOT plus ramucirumab for resectable esophagogastric adenocarcinoma
T2 - A randomized phase II/III trial of the German AIO and Italian GOIM
AU - Goetze, Thorsten O
AU - Hofheinz, Ralf-Dieter
AU - Gaiser, Timo
AU - Schmalenberg, Harald
AU - Strumberg, Dirk
AU - Goekkurt, Eray
AU - Angermeier, Stefan
AU - Zander, Thomas
AU - Kopp, Hans G
AU - Pink, Daniel
AU - Siegler, Gabriele
AU - Schenk, Michael
AU - de Vita, Ferdinando
AU - Galizia, Gennaro
AU - Maiello, Evaristo
AU - Bechstein, Wolf O
AU - Elshafei, Moustafa
AU - Loose, Maria
AU - Sookthai, Disorn
AU - Brulin, Tanita
AU - Pauligk, Claudia
AU - Homann, Nils
AU - Al-Batran, Salah-Eddin
N1 - © 2023 UICC.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - This multicenter, randomized phase II/III study evaluated the addition of the vascular endothelial growth factor receptor-2 inhibitor ramucirumab to FLOT as perioperative treatment for resectable esophagogastric adenocarcinoma. Patients received either FLOT alone (Arm A) or combined with ramucirumab followed by ramucirumab monotherapy (Arm B). The primary endpoint for the phase II portion was the pathological complete or subtotal response (pCR/pSR) rate. Baseline characteristics were comparable between both arms with a high rate of tumors signet-ring cell component (A:47% B:43%). No between-arm difference in pCR/pSR rate was seen (A:29% B:26%), therefore the transition to phase III was not pursued. Nevertheless, the combination was associated with a significantly increased R0-resection rate compared with FLOT alone (A:82% B:96%; P = .009). In addition, the median disease-free survival was numerically improved in Arm B (A:21 months B:32 months, HR 0.75, P = 0.218), while the median overall survival was similar in both treatment arms (A:45 months B:46 months, HR 0.94, P = 0.803). Patients with Siewert type I tumors receiving transthoracic esophagectomy with intrathoracic anastomosis showed an increased risk of serious postoperative complications after ramucirumab treatment, therefore recruitment of those patients was stopped after the first-third of the study. Overall, surgical morbidity and mortality was comparable, whereas more non-surgical grade ≥ 3 adverse events were observed with the combination, especially anorexia (A:1% B:11%), hypertension (A:4% B:13%) and infections (A:19% B:33%). The combination of ramucirumab and FLOT as perioperative treatment shows efficacy signals, particularly in terms of R0 resection rates, for a study population with a high proportion of prognostically poor histological subtypes, and further evaluation in this subgroup seems warranted.
AB - This multicenter, randomized phase II/III study evaluated the addition of the vascular endothelial growth factor receptor-2 inhibitor ramucirumab to FLOT as perioperative treatment for resectable esophagogastric adenocarcinoma. Patients received either FLOT alone (Arm A) or combined with ramucirumab followed by ramucirumab monotherapy (Arm B). The primary endpoint for the phase II portion was the pathological complete or subtotal response (pCR/pSR) rate. Baseline characteristics were comparable between both arms with a high rate of tumors signet-ring cell component (A:47% B:43%). No between-arm difference in pCR/pSR rate was seen (A:29% B:26%), therefore the transition to phase III was not pursued. Nevertheless, the combination was associated with a significantly increased R0-resection rate compared with FLOT alone (A:82% B:96%; P = .009). In addition, the median disease-free survival was numerically improved in Arm B (A:21 months B:32 months, HR 0.75, P = 0.218), while the median overall survival was similar in both treatment arms (A:45 months B:46 months, HR 0.94, P = 0.803). Patients with Siewert type I tumors receiving transthoracic esophagectomy with intrathoracic anastomosis showed an increased risk of serious postoperative complications after ramucirumab treatment, therefore recruitment of those patients was stopped after the first-third of the study. Overall, surgical morbidity and mortality was comparable, whereas more non-surgical grade ≥ 3 adverse events were observed with the combination, especially anorexia (A:1% B:11%), hypertension (A:4% B:13%) and infections (A:19% B:33%). The combination of ramucirumab and FLOT as perioperative treatment shows efficacy signals, particularly in terms of R0 resection rates, for a study population with a high proportion of prognostically poor histological subtypes, and further evaluation in this subgroup seems warranted.
KW - Humans
KW - Adenocarcinoma/drug therapy
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Esophageal Neoplasms/drug therapy
KW - Esophagogastric Junction/pathology
KW - Fluorouracil
KW - Leucovorin
KW - Stomach Neoplasms/drug therapy
KW - Vascular Endothelial Growth Factor A
KW - Ramucirumab
U2 - 10.1002/ijc.34495
DO - 10.1002/ijc.34495
M3 - Original Article
C2 - 36883420
SN - 0020-7136
VL - 153
SP - 153
EP - 163
JO - INTERNATIONAL JOURNAL OF CANCER
JF - INTERNATIONAL JOURNAL OF CANCER
IS - 1
ER -