Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217)

Tintelnot, Joseph; Goekkurt, Eray; Binder, Mascha; Thuss‐Patience, Peter; Lorenzen, Sylvie; Knorrenschild, Jorge Riera; Kretzschmar, Albrecht; Ettrich, Thomas Jens; Lindig, Udo; Jacobasch, Lutz; Pink, Daniel; Al‐Batran, Salah‐Eddin; Hinke, Axel; Hegewisch‐Becker, Susanna; Nilsson, Sven Erik G.; Bokemeyer, Carsten; Stein, Alexander

doi:10.1186/s12885-020-06958-3

Cited by 23 publications

(15 citation statements)

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“…Clinical benefit will be measured by OS (primary endpoint), PFS, and ORR (secondary endpoints). The recruitment is completed and the first results are expected in October 2021 [ 36 ].…”

Section: Immune Checkpoint Inhibition In the Treatment Of Gej And mentioning

confidence: 99%

Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma

Högner

Thuss‐Patience

2021

Pharmaceuticals

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Immune checkpoint inhibitors enrich the therapeutic landscape in oesophago-gastric carcinoma. With regard to oesophageal squamous cell carcinoma (ESCC), the selective PD-1 (programmed cell death receptor 1)-inhibitor nivolumab improves disease-free survival in the adjuvant therapy setting (CHECKMATE-577). In first-line treatment, ESCC patients (pts) benefit in overall survival (OS) from the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). In the second-line setting, nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181) demonstrate a benefit in OS compared with chemotherapy. These data resulted in the approval of nivolumab for the second-line treatment of advanced ESCC pts regardless of PD-L1 (programmed cell death ligand 1) status in Europe, Asia, and the USA, and pembrolizumab for pts with PD-L1 CPS (combined positivity score) ≥ 10 in Asia and the USA. Further approvals can be expected. In gastro-oesophageal junction and gastric cancer, the addition of nivolumab to chemotherapy in first-line treatment improves OS in pts with advanced disease with PD-L1 CPS ≥ 5 (CHECKMATE-649). Additionally, pembrolizumab was non-inferior to chemotherapy for OS in PD-L1 CPS ≥ 1 pts (KEYNOTE-062). In third-line treatment, nivolumab shows benefits in OS regardless of PD-L1 expression (ATTRACTION-02) with approval in Asia, and pembrolizumab prolonged the duration of response in PD-L1 positive pts (KEYNOTE-059) with approval in the USA. We discuss the recent results of the completed phase II and III clinical trials.

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“…Clinical benefit will be measured by OS (primary endpoint), PFS, and ORR (secondary endpoints). The recruitment is completed and the first results are expected in October 2021 [ 36 ].…”

Section: Immune Checkpoint Inhibition In the Treatment Of Gej And mentioning

confidence: 99%

Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma

Högner

Thuss‐Patience

2021

Pharmaceuticals

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“…The recent results of the CheckMate 649 and ATTRACTION-4 clinical trials demonstrated efficacy in advanced HER2-negative GEA ( 28 , 29 ). In HER2-positive GEA, phase II and III trials are still ongoing, evaluating the addition of anti-PD-1 therapy (as monotherapy or in combination with anti-CTLA-4) to trastuzumab +/- platin-based chemotherapy (NCT02901301, NCT03615326, NCT03409848) ( 30 , 31 ). Recently, the prespecified intermediate analysis of Keynote 811 phase III study, demonstrated an improvement in ORR with the addition of pembrolizumab to the PFT regimen (74.4% vs 51.9%; p=0.00006) ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Interest of the Addition of Taxanes to Standard Treatment in First-Line Advanced HER2 Positive Gastroesophageal Adenocarcinoma in Selective Patients

et al. 2022

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BackgroundStudies have reported a beneficial role of the addition of trastuzumab to platin-5-FU based chemotherapy in first-line advanced HER2 positive gastroesophageal adenocarcinoma (GEA). However, the effect of taxanes combined with platin-5FU + trastuzumab (PFT) is understudied.MethodsWe performed a retrospective cohort study to evaluate the interest of taxanes among HER2-positive advanced GEA patients treated with PFT. We enrolled HER2-positive advanced GEA patients who underwent treatment between January 2009 to March 2021 in seven hospitals centers in France, treated with PFT alone (S group) or with taxanes + PFT regimen (T group). The primary outcome was progression-free survival (PFS). Also, overall survival (OS), response rate, conversion surgery rate, and safety were evaluated.ResultsOverall, 65 patients received PFT-based therapy, 24 patients in the T group, and 41 patients in the S group. To avoid the selection bias, only those patients presenting an ECOG-PS of 0-1 and synchronous metastasis (21 patients in the T group and 19 patients in the S group) were included for analysis. The median PFS was 9.3 months (95%CI 7.0 to 17.2) in the T group and 5.9 months (95%CI 3.7 to 9.6) in the S group (log-rank p=0.038). Treatment by taxanes was significantly associated with a better PFS in univariate (HR 0.49; 95%CI 0.25 to 0.98, p=0.042) and multivariate Cox regression analysis (HR 0.44; 95%CI 0.21 to 0.94, p=0.033), and IPTW method (HR 0.56; 95% CI 0.34 to 0.91, p=0.019). OS was prolonged (19.0 months (95%CI 7.8 to 45.2) vs 13.0 months (95%CI 5.5 to 14.8), log-rank p=0.033) in favor of the T group. Treatment by taxanes was significantly associated with a better OS in univariate Cox regression analysis (HR 0.49; 95%CI 0.21 to 0.96, p=0.038) and IPTW method (HR 0.49; 95% CI 0.29 to 0.84, p=0.009). The response rate was higher in the T group, with conversion surgery in five patients. No treatment-related death was observed in both groups.ConclusionsGiven the improvement in PFS and OS, the addition of taxanes to standard chemotherapy could be considered as a promising treatment for selected HER2-positive advanced GEA patients, with PS 0-1 and synchronous metastasis (NCT04920747).

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“…For patients with Her2-overexpressing EGC in advanced or metastatic disease stage, the phase II INTEGA trial assesses a superior effect on OS by the chemotherapy-free combination of Her2-blockade (trastuzumab) plus immune checkpoint inhibition (nivolumab + ipilimumab) in comparison with nivolumab plus the standard first-line regimen (trastuzumab + FOLFOX chemotherapy) [40]. First results of the efficacy analysis demonstrate an increased efficacy of the combination of trastuzumab, nivolumab and FOLFOX compared with the TOGA regimen.…”

Section: Combination Of Immune Checkpoint Inhibition and Her2-targete...mentioning

confidence: 99%

Immunotherapy in Gastric Cancer

Högner

Möhler

2022

Current Oncology

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Immune checkpoint inhibition is a new standard of targeted therapy in the treatment of advanced or metastatic gastric cancer (GC) and is represented in various combinations with and without chemotherapy in every therapy line within clinical trials. In advanced adenocarcinoma of GC, gastroesophageal junction cancer (GEJC) and esophageal cancer (EC), the combination of nivolumab and chemotherapy in first-line therapy improves overall survival (OS) in PD-L1 (programmed cell death protein 1)-positive patients with approval in Europe (PD-L1 CPS (combined positivity score) ≥ 5), USA and Taiwan (CHECKMATE-649) and pembrolizumab plus chemotherapy for GEJC and EC in Europe (CPS ≥ 10) and the USA (KEYNOTE-590). Furthermore, pembrolizumab plus trastuzumab and chemotherapy show clear benefits in OS and are approved as first-line treatment of Her2 (human epidermal growth factor receptor-2)-positive tumors in the USA (KEYNOTE-811). Nivolumab demonstrates superior OS regardless of PD-L1 expression in third-line therapy with approval in Japan (ATTRACTION-02) and pembrolizumab prolonged the duration of response in PD-L1 positive patients with approval in the USA in PD-L1 CPS ≥ 1 patients (KEYNOTE-059). This review reflects the rationale and current results of phase II and III clinical trials investigating various immune checkpoint inhibitors targeting PD-L1/1 and CTLA (anticytotoxic T-lymphocyte-associated antigen)-4 in combination with and without chemotherapy and Her2-targeted therapy in GC.

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Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217)

Cited by 23 publications

References 42 publications

Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma

Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma

Interest of the Addition of Taxanes to Standard Treatment in First-Line Advanced HER2 Positive Gastroesophageal Adenocarcinoma in Selective Patients

Immunotherapy in Gastric Cancer

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