An open-label, multicenter biomarker-oriented phase II trial of sunitinib for patients with chemo-refractory advanced gastric cancer

Moehler, Markus; Mueller, Andreas; Hartmann, Jakob; Ebert, MP; Al-Batran, S-E.; Reimer, Peter; Weihrauch, Martin R.; Lordick, Florian; Trarbach, Tanja; Biesterfeld, Stefan; Kabisch, Maria; Wachtlin, Daniel; Galle, PR

doi:10.1055/s-0031-1285288

Cited by 8 publications

(6 citation statements)

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“…Fiftyseven percent of patients in this study were chemotherapy naive a much higher percentage than in other single agent phase II studies of single agent targeted therapies in metastatic gastric cancer. Compared to saracatinib, the receptor tyrosine kinase inhibitor sunitinib resulted in a median PFS of 42 days (range 37-60 days) in patients who had received multiple lines of chemotherapy [21] and a median PFS of 89 days (05% CI 50-91 days) was seen with, the Mammalian Target of Rapamycin inhibitor, everolimus [22]. As a single agent, in an unselected, [18] and data from the phase II trial [23] investigating saracatinib in patients with prostate cancer, toxicity rates generally appeared higher in our patient population.…”

Section: Discussionmentioning

confidence: 99%

A phase II trial of the Src kinase inhibitor saracatinib (AZD0530) in patients with metastatic or locally advanced gastric or gastro esophageal junction (GEJ) adenocarcinoma: a trial of the PMH phase II consortium

Mackay

McWhirter

et al. 2011

Invest New Drugs

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Section: Discussionmentioning

confidence: 99%

A phase II trial of the Src kinase inhibitor saracatinib (AZD0530) in patients with metastatic or locally advanced gastric or gastro esophageal junction (GEJ) adenocarcinoma: a trial of the PMH phase II consortium

Mackay

McWhirter

et al. 2011

Invest New Drugs

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“…For gastric tumors, total or subtotal distal gastrectomy with D2 lymphadenectomy was performed, which represents the standard of care in Germany. 10 Splenectomy and pancreatic resection were avoided whenever possible. Centers with experienced surgery departments (or established collaboration with such departments) were selected for this trial, and the surgery reports were reviewed centrally by an experienced surgeon (T.O.G.…”

Section: Methodsmentioning

confidence: 99%

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

Merx

Haag

et al. 2022

JCO

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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 (95% CI) at 24 months were 54% (38 to 71) and 77% (63 to 90) in arm A and 70% (55 to 85) and 84% (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.

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“…Surgery was scheduled 4-6 weeks after the last dose of preoperative FLOT and was conducted according to the standard-of-care requirements in German (Appendix 1, online only). 13 Surgery reports were reviewed centrally by an experienced surgeon.…”

Section: Interventionsmentioning

confidence: 99%

Perioperative Atezolizumab Plus Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel for Resectable Esophagogastric Cancer: Interim Results From the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial

Lorenzen,

Götze,

Thuss-Patience

et al. 2024

JCO

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PURPOSE This trial evaluates the addition of the PD-L1 antibody atezolizumab (ATZ) to standard-of-care fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) as a perioperative treatment for patients with resectable esophagogastric adenocarcinoma (EGA). METHODS DANTE started as multicenter, randomized phase II trial, which was subsequently converted to a phase III trial. Here, we present the results of the phase II proportion, focusing on surgical pathology and safety outcomes on an exploratory basis. Patients with resectable EGA (≥cT2 or cN+) were assigned to either four preoperative and postoperative cycles of FLOT combined with ATZ, followed by eight cycles of ATZ maintenance (arm A) or FLOT alone (arm B). RESULTS Two hundred ninety-five patients were randomly assigned (A, 146; B, 149) with balanced baseline characteristics between arms. Twenty-three patients (8%) had tumors with microsatellite instability (MSI), and 58% patients had tumors with a PD-L1 combined positive score (CPS) of ≥1. Surgical morbidity (A, 45%; B, 42%) and 60-day mortality (A, 3%; B, 2%) were comparable between arms. Downstaging favored arm A versus arm B (ypT0, 23% v 15% [one-sided P = .044]; ypT0-T2, 61% v 48% [one-sided P = .015]; ypN0, 68% v 54% [one-sided P = .012]). Histopathologic complete regression rates (pathologic complete response or TRG1a) were higher after FLOT plus ATZ (A, 24%; B, 15%; one-sided P = .032), and the difference was more pronounced in the PD-L1 CPS ≥10 (A, 33%; B, 12%) and MSI (A, 63%; B, 27%) subpopulations. Complete margin-free (R0) resection rates were relatively high in both arms (A, 96%; B, 95%). The incidence and severity of adverse events were similar in both groups. CONCLUSION Within the limitations of the exploratory nature of the data, the addition of ATZ to perioperative FLOT is safe and improved postoperative stage and histopathologic regression.

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An open-label, multicenter biomarker-oriented phase II trial of sunitinib for patients with chemo-refractory advanced gastric cancer

Cited by 8 publications

References 0 publications

A phase II trial of the Src kinase inhibitor saracatinib (AZD0530) in patients with metastatic or locally advanced gastric or gastro esophageal junction (GEJ) adenocarcinoma: a trial of the PMH phase II consortium

A phase II trial of the Src kinase inhibitor saracatinib (AZD0530) in patients with metastatic or locally advanced gastric or gastro esophageal junction (GEJ) adenocarcinoma: a trial of the PMH phase II consortium

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

Perioperative Atezolizumab Plus Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel for Resectable Esophagogastric Cancer: Interim Results From the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial

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