Resectability, conversion and resections rates, and outcomes in RAS&BRAF wildtype (wt), RAS mutant (mt) and BRAFmt metastatic colorectal cancer (mCRC) subgroups in the prospective Finnish RAXO-study.

Authors

Pia Osterlund

Pia J. Osterlund

Tampere University Hospital and University of Tampere, Department of Oncology, Tampere, Finland

Pia J. Osterlund , Emerik Osterlund , Aki Uutela , Päivi Halonen , Raija S. Kallio , Annika Ålgars , Tapio Salminen , Annamarja Lamminmäki , Leena-Maija Soveri , Raija Ristamäki , Kaisa I Lehtomäki , Hanna Stedt , Eetu Heervä , Arno Nordin , Ali Ovissi , Jari Sundström , Lasse Nieminen , Markus J Mäkinen , Ari Ristimäki , Helena Isoniemi

Organizations

Tampere University Hospital and University of Tampere, Department of Oncology, Tampere, Finland, Uppsala University and Akademiska Sjukhuset, Department of Immunology, Genetics and Pathology, Uppsala, Sweden, Helsinki University Hospital and University of Helsinki, Department of Transplantation and Liver Surgery, Helsinki, Finland, Helsinki University Hospital and University of Helsinki, Department of Oncology, Helsinki, Finland, Oulu University Hospital, Department of Oncology, Oulu, Finland, Turku University Hospital, Department of Oncology and Radiotherapy, Turku, Finland, Tampere University Hospital and Tampere University, Department of Oncology, Tampere, Finland, Kuopio University Hospital, Department of Oncology, Kuopio, Finland, Helsinki University Central Hospital and Hyvinkää Home Care, Department of Palliative Care, Helsinki and Hyvinkää, Finland, Turku University Hospital and University of Turku, Department of Oncology, Turku, Finland, Helsinki University Hospital, Department of Radiology, Helsinki, Finland, Turku University Hospital and University of Turku, Department of Pathology, Turku, Finland, University of Oulu and Oulu University Hospital, Department of Pathology, Oulu, Finland, Helsinki University Central Hospital and University of Helsinki and Genome-Scale Biology, Research Programs Unit, University of Helsinki, Helsinki, Finland, Helsinki University Central Hospital and University of Helsinki, Department Transplantation and Liver Surgery, Helsinki, Finland

Research Funding

Other Foundation
The Finnish Cancer Foundation, Finska Lakaresallskapet, Competitive state research Helsinki, Tampere, Turku, Oulu, Kuopio and Satakunta hospitals, Research funds at Tampere and Helsinki University Hospitals, Pharmaceutical/Biotech Company

Background: Outcomes of metastasectomy varies with RAS and BRAF-status, but the effect on resectability, conversion and resection rates has not been extensively studied. Methods: The prospective Finnish RAXO study (NCT01531621) included 1086 patients 2011-2018 (Osterlund et al TLRHE 2021, Isoniemi et al BJS 2021) of which 906 were included in this secondary endpoint analysis. Excluded had missing KRAS/NRAS/BRAF-V600E test, were untreatable or had an atypical BRAF mutation. We studied repeated centralized resectability assessment, conversion and resectability rates in mCRC, and overall survival (OS) after resection and/or local ablative therapy (LAT) and systemic therapy. Results: Included were 289 RAS&BRAFwt, 529 RASmt (overrepresented) and 88 BRAFmt, with median age 65.8/66.1/66.9 years. Demographics per RAS&BRAFwt, RASmt and BRAFmt showed significant differences in male proportion (68/61/39%), ECOG PS 2-3 groups (16/14/25%), primary tumour location (right colon 16/30/69%, left colon 47/34/17%, rectum 38/36/14%), but not for Charlson comorbidity index, BMI, resection of primary, synchronous presentation or adjuvant therapy (Bonferroni corrected Chi-square). Metastatic profile was different for liver (78/74/61% per RAS&BRAFwt, RASmt and BRAFmt), lung (24/35/28%) and peritoneal (15/15/32%) metastases, but not for lymph nodes or other sites, nor for number of metastatic sites (1 in 53/54/52%). Upfront resectability rates were different with 32/29/15% for RAS&BRAFwt, RASmt and BRAFmt, respectively, as were conversion rates with 16/13/7%, and resection/LAT rates with 45/37/17%, respectively. Kaplan-Meier median OS estimate in R0/1/2-resected and/or LAT group (n = 342) was 83/69/30 months for RAS&BRAFwt, RASmt and BRAFmt groups, respectively and 5-year OS-rates 67/60/24%, with Cox HR ref/1.53 (95% CI 1.04-2.25)/3.11 (1.49-6.49). In the “systemic therapy only” (n = 564) OS was 29/21/15 months and 5-year OS-rates 11/6/2% respectively, with HR ref/1.43 (1.15-1.76)/2.34 (1.73-3.17). Resection/LAT patients had improved OS over “systemic therapy only” patients in all subgroups, HR 5.74 (3.90-8.44)/5.06 (3.92-6.55)/2.89 (1.43-5.86). Conclusions: There were significant differences in resectability, conversion and resection/LAT rates according to RAS&BRAFwt, RASmt and BRAFmt status. OS was also significantly longer for RAS&BRAFwt versus either mutant. Resected/LAT had better OS than “systemic therapy alone” patients in all subgroups. Clinical trial information: NCT01531621

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gastrointestinal Cancer—Colorectal and Anal

Track

Gastrointestinal Cancer—Colorectal and Anal

Sub Track

Epidemiology/Outcomes

Clinical Trial Registration Number

NCT01531621

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 3532)

DOI

10.1200/JCO.2021.39.15_suppl.3532

Abstract #

3532

Poster Bd #

Online Only

Abstract Disclosures

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