Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster session 15

543P - Tumor mutational burden (TMB), BRAF status, and C-reactive protein (CRP) predict response to first-line alternating oxaliplatin-based chemotherapy and nivolumab in metastatic microsatellite-stable (MSS) colorectal cancer (CRC)

Date

14 Sep 2024

Session

Poster session 15

Topics

Clinical Research;  Cytotoxic Therapy;  Tumour Immunology;  Molecular Oncology;  Genetic and Genomic Testing;  Immunotherapy

Tumour Site

Colon and Rectal Cancer

Presenters

Anne Ree

Citation

Annals of Oncology (2024) 35 (suppl_2): S428-S481. 10.1016/annonc/annonc1588

Authors

A.H. Ree1, P.A. Bousquet1, H.L. Nilsen2, T. Lüders2, S. Wang2, T. Visnovska2, D.L. Bordin2, E. Høye3, H.M. Hamre1, C. Kersten4, E. Hofsli5, M.G. Guren6, H. Sorbye7, J.P. Berg8, K. Flatmark9, S. Meltzer1

Author affiliations

  • 1 Oncology, Akershus University Hospital, 1478 - Lorenskog/NO
  • 2 Clinical Molecular Biology, Akershus University Hospital, 1478 - Lorenskog/NO
  • 3 Tumor Biology, Oslo University Hospital, 0424 - Oslo/NO
  • 4 Cancer Research, Sorlandet Hospital, 4615 - Kristiansand/NO
  • 5 Cancer Clinic, St Olav's Hospital, 7006 - Trondheim/NO
  • 6 Oncology, Oslo University Hospital, 0424 - Oslo/NO
  • 7 Oncology, Haukeland University Hospital, 5021 - Bergen/NO
  • 8 Institute Of Clinical Medicine, University of Oslo, 0316 - Oslo/NO
  • 9 Gastroenterological Surgery, Oslo University Hospital, 0424 - Oslo/NO

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 543P

Background

The randomized METIMMOX trial evaluated short-course oxaliplatin-based chemotherapy (FLOX) alternating with nivolumab for previously untreated, unresectable abdominal metastases from MSS-CRC. A subgroup of patients assigned to this experimental treatment had remarkably extended progression-free survival (PFS) compared to the control-group patients given standard FLOX chemotherapy with median PFS 9.3 months. We explored if tumor mutations or patients’ systemic inflammation might provide insights into responsiveness to the METIMMOX regimen.

Methods

Patients were randomly assigned to the control group of FLOX (oxaliplatin, 5-fluorouracil, folinic acid) Q2W or the experimental group of alternating 2 cycles each of FLOX Q2W and nivolumab Q2W, with prespecified break periods. Radiologic response assessment was done every 8 weeks with PFS as the primary endpoint. Tumor biopsies were sequenced with the TruSight Oncology 500 assay to identify driver mutations and calculate TMB (in mutations/megabase). CRP (in mg/L) was analyzed at every study visit.

Results

Sequencing data were acquired from 34 experimental-group patients with median PFS 9.9 months (min 1.9, max 41.6). Median TMB was 8.0 (min 0.8, max 12.2). Four cases were BRAF-V600E. The median TMB value or BRAF status distinguished between patient groups (p = 0.0003, log-rank test) with median PFS 19.8 months (95% CI 11.3-28.3; TMB>8.0/BRAF-V600E, n = 17) and median PFS 5.8 months (95% CI 1.4-10.2; TMB8.0/BRAF-V600E cases with CRP<5.0 when starting nivolumab (n = 11) attained median PFS 34.9 months (95% CI 6.8-63.0).

Conclusions

TMB>8.0 or BRAF-V600E, with the additional inhibitory effect of the initial chemotherapy on systemic inflammation, was associated with extended PFS for patients with abdominal metastases from MSS-CRC given first-line alternating oxaliplatin-based chemotherapy and nivolumab.

Clinical trial identification

NCT03388190.

Editorial acknowledgement

Legal entity responsible for the study

Akershus University Hospital.

Funding

Norwegian Cancer Society.

Disclosure

A.H. Ree: Financial Interests, Institutional, Research Funding: Bristol-Myers Squibb; Financial Interests, Personal, Expert Testimony: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Takeda. H.M. Hamre: Financial Interests, Personal, Expert Testimony: Bayer, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, InCyte. C. Kersten: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche. H. Sorbye: Financial Interests, Personal, Expert Testimony: Ipsen, Pierre Fabre, Daiichi Sankyo, SAM Nordic; Financial Interests, Personal, Advisory Board: AAA Pharma. S. Meltzer: Financial Interests, Personal, Advisory Board: GSK. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.