Trastuzumab in combination with 5‐fluorouracil, leucovorin, oxaliplatin and docetaxel as perioperative treatment for patients with human epidermal growth factor receptor 2‐positive locally advanced esophagogastric adenocarcinoma: A phase <scp>II</scp> trial of the Arbeitsgemeinschaft Internistische Onkologie Gastric Cancer Study Group

Hofheinz, Ralf–Dieter; Hegewisch-Becker, S.; Kunzmann, Volker; Thuss‐Patience, Peter; Fuchs, Martin; Homann, Nils; Graeven, Ullrich; Schulte, Nadine; Merx, Kirsten; Pohl, Michael; Held, Swantje; Keller, R; Tannapfel, Andrea; Al‐Batran, Salah‐Eddin

doi:10.1002/ijc.33696

Cited by 66 publications

(57 citation statements)

References 22 publications

(40 reference statements)

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“…[25] However, a phase II study observed one severe cardiac disorder, potentially attributable to the addition of trastuzumab to FLOT. [17] The pathological complete response (pCR) rate was 16% (range 9.6-22.2%) in three studies. [16][17][18] On the other hand, no survival benefit was demonstrated with the addition of trastuzumab to six weeks of chemoradiotherapy in preliminary results of a large randomized study (n=203).…”

Section: Single Her2 Targeting With Trastuzumabmentioning

confidence: 95%

“…The included studies demonstrated feasibility of the addition of trastuzumab to conventional cytotoxic therapy. [16][17][18]23,25] No increase in treatment-related toxicities, as well as no unexpected safety findings were observed by adding trastuzumab to the treatment regimens. [16][17][18]25] Two studies reported relatively high incidences of grade ≥3 diarrhea (33%) and neutropenia (28%), although toxicities were manageable.…”

Section: Single Her2 Targeting With Trastuzumabmentioning

confidence: 97%

“…[16][17][18]23,25] No increase in treatment-related toxicities, as well as no unexpected safety findings were observed by adding trastuzumab to the treatment regimens. [16][17][18]25] Two studies reported relatively high incidences of grade ≥3 diarrhea (33%) and neutropenia (28%), although toxicities were manageable. [17,18] Furthermore, trastuzumab did not result in an increase of cardiac toxicity, with a mean left ventricular ejection fraction of 57% pre-treatment compared to 56% posttreatment in a phase I/II trial [15], as well as no reported cardiotoxicity in a large randomized study with 203 patients.…”

Section: Single Her2 Targeting With Trastuzumabmentioning

confidence: 97%

“…Several studies investigated the tolerability and efficacy of the addition of trastuzumab to chemo(radio)therapy for the curative treatment of patients with HER2 positive GEA. [15][16][17][18]23] The majority of studies were small nonrandomized phase I/II studies (n=36, range 19-203), reporting on the safety and efficacy of the addition of trastuzumab to neoadjuvant, perioperative, or adjuvant chemo(radio)therapy. The included studies demonstrated feasibility of the addition of trastuzumab to conventional cytotoxic therapy.…”

Section: Single Her2 Targeting With Trastuzumabmentioning

confidence: 99%

“…[16][17][18]25] Two studies reported relatively high incidences of grade ≥3 diarrhea (33%) and neutropenia (28%), although toxicities were manageable. [17,18] Furthermore, trastuzumab did not result in an increase of cardiac toxicity, with a mean left ventricular ejection fraction of 57% pre-treatment compared to 56% posttreatment in a phase I/II trial [15], as well as no reported cardiotoxicity in a large randomized study with 203 patients. [25] However, a phase II study observed one severe cardiac disorder, potentially attributable to the addition of trastuzumab to FLOT.…”

Section: Single Her2 Targeting With Trastuzumabmentioning

confidence: 99%

See 4 more Smart Citations

A systematic review of HER2 blockade for the curative treatment of gastroesophageal adenocarcinoma: Successes achieved and opportunities ahead

Stroes

Ende

Derks

et al. 2021

Cancer Treatment Reviews

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Single Her2 Targeting With Trastuzumabmentioning

confidence: 95%

Section: Single Her2 Targeting With Trastuzumabmentioning

confidence: 97%

Section: Single Her2 Targeting With Trastuzumabmentioning

confidence: 97%

Section: Single Her2 Targeting With Trastuzumabmentioning

confidence: 99%

Section: Single Her2 Targeting With Trastuzumabmentioning

confidence: 99%

See 3 more Smart Citations

A systematic review of HER2 blockade for the curative treatment of gastroesophageal adenocarcinoma: Successes achieved and opportunities ahead

Stroes

Ende

Derks

et al. 2021

Cancer Treatment Reviews

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Perioperative FLOT plus ramucirumab for resectable esophagogastric adenocarcinoma: A randomized phase II/III trial of the German AIO and Italian GOIM

Goetze

Hofheinz

Gaiser

et al. 2023

Intl Journal of Cancer

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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.

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Perioperative therapy with FLOT4 significantly increases survival in patients with gastroesophageal and gastric cancer in a large real‐world cohort

Möhring

Mańczak

Timotheou

et al. 2023

Intl Journal of Cancer

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In 2019, the FLOT4 protocol was established as the new standard for perioperative therapy in patients with locally advanced gastroesophageal and gastric cancer.Whether this protocol is beneficial in a real-world setting remains a question with limited answers to date. In our study, a large cohort of unselected patients treated with FLOT4 was analyzed and compared to protocols based on 5-FU/platinum derivative. This retrospective analysis included patients with locally advanced gastroesophageal and gastric cancer treated with perioperative FLOT or 5-FU/platinum derivative at University Hospital, Bonn between 2010 and 2022 in a curative setting (n = 99).Overall survival, disease-free survival, therapy response and therapy complications were analyzed. Patients treated with FLOT showed a statistically significant longer median overall survival of 57.8 vs 28.9 months (HR: 0.554, 95% CI: 0.317-0.969, P = .036). Moreover, pathological tumor regression (pTR) was significantly higher in the FLOT group compared to the 5-FU/platinum group (P = .001).

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Cited by 66 publications

References 22 publications

A systematic review of HER2 blockade for the curative treatment of gastroesophageal adenocarcinoma: Successes achieved and opportunities ahead

A systematic review of HER2 blockade for the curative treatment of gastroesophageal adenocarcinoma: Successes achieved and opportunities ahead

Perioperative FLOT plus ramucirumab for resectable esophagogastric adenocarcinoma: A randomized phase II/III trial of the German AIO and Italian GOIM

Perioperative therapy with FLOT4 significantly increases survival in patients with gastroesophageal and gastric cancer in a large real‐world cohort

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