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Clinical Studies

TAS-102, Irinotecan, and bevacizumab in pre-treated metastatic colorectal cancer (TABAsCO), a phase II clinical trial

British Journal of Cancer (2024)Cite this article

Subjects

Abstract

Background

The efficacy of FOLFIRI plus an antiangiogenesis biologic agent as 2nd line therapy for metastatic colorectal adenocarcinoma is limited. TAS-102 is a novel oral antimetabolite with a distinct mechanism of action from fluoropyrimidines. We evaluated the antitumour efficacy of TAS-102, irinotecan and bevacizumab in patients with pre-treated, advanced colorectal adenocarcinoma in a multicenter, phase II, single-arm study.

Methods

Patients with advanced colorectal adenocarcinoma who had progressed after oxaliplatin and fluoropyrimidine and were eligible for treatment with bevacizumab were treated with irinotecan, bevacizumab, and TAS-102 in 28-day cycles. The primary endpoint was progression-free survival (PFS).

Results

We enrolled 35 evaluable patients. The study was positive. The median PFS was 7.9 (90% CI 6.2–11.8) months (vs. 6 months in historical control, p = 0.018). The median overall survival was 16.5 (90% CI 9.8–17.5) months. Sixty-seven per cent of patients experienced grade 3 or higher treatment-related adverse events. The most common toxicities were hematological (neutropenia) and gastrointestinal (diarrhoea, nausea, and vomiting).

Conclusions

Irinotecan, TAS-102 and bevacizumab is an active 2nd line therapy for patients with metastatic colorectal adenocarcinoma. Neutropenia is common and can affect dose density/intensity mandating use of G-CSF. A randomized study versus standard-of-care therapy is warranted.

Clinical trial registration

ClinicalTrials.gov NCT04109924.

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Fig. 1: CONSORT Diagram.
Fig. 2: Survival Outcomes.
Fig. 3: Antitumor Efficacy.

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Data availability

De-identified clinical data will be available upon request to the corresponding author. The raw RNA sequencing data can be accessed from https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275628.

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Acknowledgements

TAS-102 was provided for free by Taiho Oncology. This work was partially supported by the National Cancer Institute (NCI) grants R37CA282430 to Dr. Christos Fountzilas and P30CA016056 involving the use of Roswell Park Comprehensive Cancer Center’s Biostatistics and Bioinformatics Shared Resource, Genomics Shared Resource, and the Pathology Network Shared Resource. The initial results of this study were presented in the American Society of Clinical Oncology 2023 Annual Meeting (Abstract 3590, Poster 290).

Funding

This study was funded by the National Comprehensive Cancer Network Oncology Research Program through a grant provided by Taiho Oncology. The funder had no role in the design or interpretation of study results.

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Authors and Affiliations

  1. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Patrick M. Boland & Howard S. Hochster

  2. Roswell Park Comprehensive Cancer Center, Elm & Carlton St, Buffalo, NY, USA

    Sarbajit Mukherjee, Renuka V. Iyer, Andrei Bakin, Jianxin Wang, Sarah Chatley, Beth Cahill, Deepak Vadehra, Kristopher Attwood & Christos Fountzilas

  3. Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL, USA

    Iman Imanirad

  4. Fox Chase Cancer Center, Philadelphia, PA, USA

    Namrata Vijayvergia

  5. Monmouth Hematology Oncology, RWJBarnanas Health, West Long Branch, NJ, USA

    Seth D. Cohen

  6. Program in Women’s Oncology, Women & Infants Hospital, Brown University, Providence, RI, USA

    Medhavi Gupta

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Contributions

Patrick Boland - conceptualization, formal analysis, funding acquisition, data curation, methodology, project administration, and writing (review and editing), Sarbajit Mukherjee - data curation, and writing (review and editing), Iman Imanirad - project administration, data curation, and writing (review and editing), Namrata Vijayvergia project administration, data curation, and writing (review and editing), Seth Cohen - data curation, and writing (review and editing), Medhavi Gupta - methodology, and writing (review and editing), Renuka Iyer - data curation, and writing (review and editing), Andrei Bakin - formal analysis, and writing (review and editing), Jianxin Wang - formal analysis, data curation, methodology, and writing (review and editing), Sarah Chatley - data curation, and writing (review and editing), Beth Cahill - data curation, and writing (review and editing), Deepak Vadehra - data curation, and writing (review and editing), Kristopher Attwood - formal analysis, data curation, methodology, and writing (review and editing), Howard Hochster - data curation, and writing (review and editing), Christos Fountzilas - formal analysis, funding acquisition, data curation, methodology, project administration, and writing (original draft, review and editing).

Corresponding author

Correspondence to Christos Fountzilas.

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Competing interests

Dr. Christos Fountzilas has research support for this clinical trial from the National Comprehensive Cancer Network Oncology Research Program (paid to the institute). He has research support from the National Comprehensive Cancer Network Foundation, Taiho Oncology, Pfizer Inc, and Merck Sharp & Dohme Corp (paid to the institute) unrelated to this study. Dr. Sarbajit Mukherjee has received research funding from Ipsen Biopharmaceuticals (paid to the institute) unrelated to this study. Dr. Iman Imanirad has received advisory board compensation from Eisai Co, Ltd, unrelated to this study.

Ethics approval and consent to participate

The study was conducted according to the Declaration of Helsinki principles and approved by the Institutional Review Boards (IRB) from all participating institutions (Roswell Park Comprehensive Cancer Center, Rutgers Cancer Institute of New Jersey, Moffitt Cancer Center, and Fox Chase Comprehensive Cancer Center). All patients provided informed consent prior to study participation. All patients providing tumor samples for whole transcriptome sequencing (de-identified Roswell Park IRB-approved protocols BDR 155422 and BDR 151721) had provided universal informed consent for use of tumor samples in research.

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Boland, P.M., Mukherjee, S., Imanirad, I. et al. TAS-102, Irinotecan, and bevacizumab in pre-treated metastatic colorectal cancer (TABAsCO), a phase II clinical trial. Br J Cancer (2024). https://doi.org/10.1038/s41416-024-02845-x

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