607P - Impact of primary tumour sidedness (PTS) on demographics, resectability, and outcome after metastasectomy +/- local ablative therapy (LAT), or systemic therapy in metastatic colorectal cancer patients (a RAXO substudy)

Background

Primary tumour sidedness (PTS) in mCRC is prognostic and predictive for anti-EGFR efficacy, progression-free (PFS) and overall survival (OS). We aimed to investigate the impact of (PTS) on demographics, resectability, and outcomes of metastasectomy, local ablative therapy (LAT) and systemic therapy.

Methods

The prospective Finnish real-life RAXO study (NCT01531621) included 1086 patients 2012-2018 (Osterlund, TLRHE 2021). Bonferroni corrected ꭓ2 <0.05, Kaplan-Meier estimates, and Cox regression were analysed. P-value <0.05 denoted with*.

Results

PTS was right in 310 (29%) and left (colon/rectum) in 770 (61%), with multiple primaries excluded. Patients with right-sided tumours more often had female sex, age >70 years, unresectable metastases upfront, mucinous & signet cell histology, high-grade differentiation, RAS and BRAF mutations, dMMR, regional and distant lymph node metastases, peritoneal and less typical metastases. Patients with left-sided tumours had more liver and lung metastases. There was no difference in ECOG, synchronous presentation, T-stage, or number of metastatic sites. Right vs left PTS was associated with less upfront resectable (26% vs 30%*) and borderline resectable (14% vs 18%*) metastases. Final resectability (upfront + converted resectable) was also lower (32% vs 45%*), and fewer patients had metastasectomy/LAT (33% vs 41%*). Median OS from mCRC diagnosis for right and left was 21 vs 35 months (HR 0.59, CI95% 0.51-0.69); after R0-1 metastasectomy 80 vs 86 months, after R2/LAT 24 vs 50* months, and 18 vs 23* months for systemic therapy only., PFS in systemic therapy only was 8.9 vs 10.0* months (HR 0.82, 0.69-0.94). In multivariable analysis for OS right PTS, RAS and BRAF status, N-stage, and unresectable metastases upfront remained significant but not female sex, age >70 or dMMR status.

Conclusions

Right-sided PTS associates with several negative prognostic and predictive factors but is an independent negative prognostic factor in multivariable analysis. Resectability and metastasectomy/LAT rates are slightly lower in right primaries and outcomes slightly worse but still “excellent”.

Clinical trial identification

NCT01531621; EudraCT 2011-003158-24.

Editorial acknowledgement

Legal entity responsible for the study

The RAXO study group represented by the authors.

Funding

Amgen (unrestricted grant), Eli Lilly and Company, Merck KGaA, Roche Oy, Sanofi and Servier (unrestricted grant).

Disclosure

P.J. Osterlund: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Merck, MSD, Pierre Fabre, Sanofi, Sobi, Incyte, Daiichi Sankyo/AstraZeneca, Eisai, Roche; Financial Interests, Personal, Invited Speaker: Eisai/Ewopharma, Novartis, Roche, Servier, Nordic Drugs, Nutricia, Fresenius Kabi, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, FIMEA expert testimony: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Amgen, Servier; Financial Interests, Institutional, Local PI: Incyte; Financial Interests, Institutional, Coordinating PI: Roche, Pfizer; Non-Financial Interests, Member: Colores patient advocacy group; Non-Financial Interests, Member, Board member: Finnish cancer society. E. Osterlund: Financial Interests, Personal, Advisory Board: Amgen, Roche; Financial Interests, Institutional, Research Grant, PI:s institution: Amgen, Eli Lilly, Merck; Non-Financial Interests, Personal, Advisory Board: Merck, Servier; Financial Interests, Institutional, Research Funding, PI:s institution: Roche; Financial Interests, Institutional, Research Funding, PI's institution: Sanofi, Servier. P. Halonen: Financial Interests, Personal, Invited Speaker, Advisory board: Amgen; Financial Interests, Institutional, Research Grant, PI's institution: Amgen, Servier; Financial Interests, Institutional, Research Funding, PI's institution: Eli Lilly, Merck, Roche, Sanofi; Non-Financial Interests, Personal, Advisory Board: Merck, Servier; Financial Interests, Personal, Advisory Board: Roche. L. Soveri: Financial Interests, Institutional, Advisory Board: Amgen, Roche, Merck, Servier. A. Nordin: Financial Interests, Institutional, Research Grant, PI's institution: Amgen, Servier; Financial Interests, Institutional, Research Funding, PI's institution: Merck, Eli Lilly, Roche, Sanofi. A. Uutela: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Institutional, Research Grant: Amgern, Eli Lilly, Merck; Financial Interests, Institutional, Research Funding: Roche, Sanofi, Servier. T. Salminen: Financial Interests, Personal, Advisory Board: Amgen, Roche; Financial Interests, Institutional, Research Grant: Eli Lilly, Amgen; Financial Interests, Institutional, Research Funding: Merck, Roche, Sanofi; Financial Interests, Institutional, Advisory Board: Servier. K.I. Lehtomaki: Financial Interests, Personal, Advisory Board: Amgen, Roche; Financial Interests, Institutional, Research Grant: Amgen, Eli Lilly, Merck; Non-Financial Interests, Personal, Advisory Board: Merck, Servier; Financial Interests, Institutional, Research Funding: Roche, Sanofi, Servier; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca. S. Aho: Financial Interests, Personal, Advisory Board: Amgen, Roche; Financial Interests, Institutional, Research Grant, Pi's institution: Amgen, Eli Lilly, Merck; Non-Financial Interests, Personal, Advisory Board: Merck, Servier; Financial Interests, Institutional, Research Funding, Pi's institution: Roche , Sanofi, Servier. A. Algars: Financial Interests, Personal, Advisory Board: Amgen, Merck, Roche; Financial Interests, Institutional, Research Grant, PI:s institution: Amgen, Merck, Sanofi, Servier; Financial Interests, Institutional, Research Grant, PI:s institiution: Eli Lilly; Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Personal, Advisory Board: Servier. R. Ristamaki: Financial Interests, Institutional, Research Grant, PI's institution: Amgen, Servier; Financial Interests, Institutional, Research Funding, PI's institution: Sanofi, Eli Lilly, Merck; Financial Interests, Institutional, Sponsor/Funding, PI's institution: Roche; Financial Interests, Personal, Advisory Board: Amgen, Roche, Merck, AstraZeneca. E. Heerva: Financial Interests, Personal, Advisory Board: Amgen, Merck, Roche, Servier; Financial Interests, Institutional, Other, Institutional grant: Eli Lilly; Financial Interests, Institutional, Other, Instutional grant: Sanofi. R. Kallio: Financial Interests, Personal, Advisory Board: Amgen, Eli Lilly, Merck, Roche, Sanofi, Servier; Financial Interests, Personal, Invited Speaker: merck. A. Lamminmäki: Financial Interests, Personal, Advisory Board: Amgen, Merck, Roche, Servier; Financial Interests, Institutional, Research Grant: Amgen, Eli Lilly, Merck, Roche, Sanofi, Servier. H.P. Stedt: Financial Interests, Personal, Advisory Board: Amgen, Eisai, MSD, Pierre Fabre; Financial Interests, Institutional, Research Grant, PI's institution: Amgen, Eli Lilly, Merck; Financial Interests, Personal, Other, Conference costs: Bayer, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, + Conference costs: Bristol Myers Squibb, Merck, Roche; Financial Interests, Institutional, Research Funding, PI's institution: Roche, Sanofi, Servier. T.T. Muhonen: Financial Interests, Personal, Advisory Board: Amgen. T. Kuopio: Financial Interests, Institutional, Research Grant, PI's institution: Amgen, Servier; Financial Interests, Institutional, Research Funding, PI's institution: Sanofi, Merck, Roche; Financial Interests, Institutional, Advisory Board, PI's institution: Eli Lilly. J.T. Kononen: Financial Interests, Personal, Invited Speaker: Merck, Roche, Incyte, AstraZeneca; Financial Interests, Personal, Full or part-time Employment: Docrates; Financial Interests, Personal, Stocks/Shares: Biopsense; Financial Interests, Institutional, Research Grant: Amgen, Eli Lilly, Merck, Roche, Sanofi, Servier. B. Glimelius: Financial Interests, Institutional, Research Funding: Amgen. H. Isoniemi: Financial Interests, Institutional, Research Funding: Amgen, Servier, Sanofi, Roche, Merck, Eli Lilly and Company; Non-Financial Interests, Personal, Advisory Board: Servier.