Dataset Information

Integrative immune transcriptomic classification improves patient selection for precision immunotherapy in advanced gastro-oesophageal adenocarcinoma.

ABSTRACT:

Background

Advanced gastro-oesophageal cancer (GEA) treatment has been improved by the introduction of immune checkpoint inhibitors (CPIs), yet identifying predictive biomarkers remains a priority, particularly in patients with a combined positive score (CPS) < 5, where the benefit is less clear. Our study assesses certain immune microenvironment features related to sensitivity or resistance to CPIs with the aim of implementing a personalised approach across CPS < 5 GEA.

Design

Through integrative transcriptomic and clinicopathological analyses, we studied in both a retrospective and a prospective cohort, the immune tumour microenvironment features. We analysed the cell types composing the immune infiltrate highlighting their functional activity.

Results

This integrative study allowed the identification of four different groups across our patients. Among them, we identified a cluster whose tumours expressed the most gene signatures related to immunomodulatory pathways and immunotherapy response. These tumours presented an enriched immune infiltrate showing high immune function activity that could potentially achieve the best benefit from CPIs. Finally, our findings were proven in an external CPI-exposed population, where the use of our transcriptomic results combined with CPS helped better identify those patients who could benefit from immunotherapy than using CPS alone (p = 0.043).

Conclusions

This transcriptomic classification could improve precision immunotherapy for GEA.

SUBMITTER: Cabeza-Segura M

PROVIDER: S-EPMC9727124 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Integrative immune transcriptomic classification improves patient selection for precision immunotherapy in advanced gastro-oesophageal adenocarcinoma.

Cabeza-Segura Manuel M Gambardella Valentina V Gimeno-Valiente Francisco F Carbonell-Asins Juan Antonio JA Alarcón-Molero Lorena L González-Vilanova Arturo A Zuñiga-Trejos Sheila S Rentero-Garrido Pilar P Villagrasa Rosana R Gil Mireia M Durá Ana A Richart Paula P Alonso Noelia N Huerta Marisol M Roselló Susana S Roda Desamparados D Tarazona Noelia N Martínez-Ciarpaglini Carolina C Castillo Josefa J Cervantes Andrés A Fleitas Tania T

British journal of cancer 20221017 12

<h4>Background</h4>Advanced gastro-oesophageal cancer (GEA) treatment has been improved by the introduction of immune checkpoint inhibitors (CPIs), yet identifying predictive biomarkers remains a priority, particularly in patients with a combined positive score (CPS) < 5, where the benefit is less clear. Our study assesses certain immune microenvironment features related to sensitivity or resistance to CPIs with the aim of implementing a personalised approach across CPS < 5 GEA.<h4>Design</h4>Th ...[more]

PMID: 36253523

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Project description:BACKGROUND:TP300, a recently developed synthetic camptothecin analogue, is a highly selective topoisomerase I inhibitor. A phase I study showed good safety and tolerability. As camptothecins have proven active in oesophago-gastric adenocarcinomas, in this phase II study we assessed the efficacy and safety of TP300 in patients with gastric or gastro-oesophageal junction (GOJ) adenocarcinomas. METHODS:Eligible patients had metastatic or locally advanced gastric or Siewert Types II or III GOJ inoperable adenocarcinoma. Patients were chemotherapy naïve unless this had been administered in the perioperative setting. TP300 was administered as a 1-h intravenous infusion every 3 weeks (a cycle) for up to 6 cycles at a starting dose of 8 mg/m2 with intra-patient escalation to 10 mg/m2 from cycle 2 in the absence of dose-limiting toxicity. Tumour responses (RECIST 1.1) were assessed every 6 weeks. Toxicity was recorded by NCI-CTCAE version 3.0. Using a modified two-stage Simon design (Stage I and II), a total of 43 patients were to be included providing there were 3 of 18 patients with objective response in Stage I of the study. RESULTS:In Stage I of the study 20 patients (14 males, 6 females), median age 67 years (range 40?-?82), performance status ECOG 0/1, with GC [14] or GOJ carcinoma [6] were enrolled. Of the 16 evaluable patients, 11 received the planned dose increase to 10 mg/m2 at cycle 2, 2 decreased to 6 mg/m2, and 3 continued on 8 mg/m2. There were no objective responses after 2 cycles of treatment. Twelve patients had stable disease for 1?-?5 months and 4 had progressive disease. Median progression free survival (PFS) was 4.1 months (CI [1.6?-?4.9]), median time to progression (TTP) was 2.9 months (CI [1.4?-?4.2]). Grade 3/4 toxicities (worst grade all cycles) included 7 patients (35 %) with neutropenia, 4 patients (20 %) with anaemia, 2 patients (10 %) with thrombocytopenia, and 3 patients (15 %) with fatigue. This study was terminated at the end of Stage I due to a lack of the required (3/18) responders. CONCLUSIONS:This study of TP300 showed good drug tolerability but it failed to demonstrate sufficient efficacy as measured by radiological response. TRIAL REGISTRATION:EU-CTR 2009-012097-12 2009-09-03.

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Dataset Information

Integrative immune transcriptomic classification improves patient selection for precision immunotherapy in advanced gastro-oesophageal adenocarcinoma.

Background

Design

Results

Conclusions

Publications

Integrative immune transcriptomic classification improves patient selection for precision immunotherapy in advanced gastro-oesophageal adenocarcinoma.

Similar Datasets

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