394P - Impact of gender on demographics, resectability, resections, systemic treatment, adverse events and outcomes in metastatic colorectal cancer (mCRC) patients (RAXO-study)

Background

Gender impacts tumour sidedness, RAS/BRAF mutations and adverse events, but data on resectability and conversion rates and outcomes are scarce.

Methods

The prospective Finnish real-life RAXO study included 1086 patients 2012-2018 (Osterlund et al TLRHE 2021). We assessed repeated centralized resectability in mCRC, and overall survival (OS), adverse events, and Quality of life (QoL) with 15D after metastasectomy, local ablative therapy (LAT) and systemic therapy. Bonferroni corrected ꭓ2 <0.05 denoted with*. Kaplan-Meier estimates and Cox regression were analysed.

Results

Males (n=656, 60%) versus females (n=430) had more comorbidities, rectal primaries, liver metastases, or RAS mutations*. Females had more right-sided primaries, poorly differentiated tumours, peritoneal metastases, rare metastases, BRAF mutations, MSI-H, anaemia, thrombocytosis, elevated CRP or ALP*. No differences were seen for age, ECOG PS, leucocytosis, lung, or lymph node metastases. Upfront resectable were 28/29% of males/females, borderline 17/16%, and non-resectable 55/55%. In upfront local vs centralised assessment resectability was underestimated in 39% of both genders. Successfully converted were 19/16%. R0/1-resections were performed in 30/30%, R2-resection/LAT in 7/7%; with liver procedure in 31/27%, lung 8/7%, cytoreductive 2/8%*, and rare metastasectomies 5/10%*. Median OS was 30.2/29.4 months (HR 1.03, CI 95% 0.89-1.19). OS was similar in R0/1-resected, R2/LAT, or “Systemic only” groups. Gr 5 toxicity was seen in 1.1/0.5%. Worst haematologic toxicity was gr 3-4 in 26/34%* and non-haematologic gr 3-5 in 62/66%, with more gr 3-4 anaemia, neutropenia, and nausea in females. Mean QoL with 15D during neoadjuvant therapy was 0.91/0.86*, <6 months from resection 0.90/0.85*, 6-18 months 0.91/0.91, >18 months 0.89/0.90, and during 1^st line systemic 0.86/0.87.

Conclusions

Sidedness, RAS/BRAF mutations, MSI-H, and metastatic sites and thus metastasectomies differed between genders. Resectability and conversion rates were similar. Resection/LAT was performed in 37% of both genders, with excellent and similar survival. Adverse event differences were noted.

Clinical trial identification

NCT01531621; EudraCT 2011-003158-24.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Amgen (unrestricted grant), Lilly, Merck KGaA, Roche Finland, Sanofi and Servier (unrestricted grant).

Disclosure

P.J. Osterlund: Financial Interests, Personal, Advisory Board: Amgen, Astra Zeneca, Bayer, MSD, Pierre Fabre, Sanofi, Sobi; Financial Interests, Personal, Invited Speaker, Also advisory boardInstitutional research funding: Eisai; Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Novartis, Nordic Drugs, Incyte, Fresenius Kabi; Financial Interests, Personal, Invited Speaker, Also advisory board: Roche; Financial Interests, Personal, Invited Speaker, Also advisory board without compensation: Servier; Financial Interests, Personal, Invited Speaker, Writing engagement: Nutricia; Financial Interests, Personal, Expert Testimony, FIMEA expert testimony: BMS; Financial Interests, Personal, Advisory Board, In collaboration with Astra Zeneca: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Amgen, Servier; Financial Interests, Institutional, Invited Speaker: Incyte; Non-Financial Interests, Member: Colores patient advocacy group; Non-Financial Interests, Member, Board member: Finnish cancer society. T. Salminen: Financial Interests, Personal, Advisory Board: amgen, roche, merck, Sanofi; Financial Interests, Personal, Research Grant: amgen; Financial Interests, Personal, Advisory Board, institutional unrestricted grant: Servier; Financial Interests, Institutional, Research Grant: Lilly, Sanofi. K.I. Lehtomaki: Financial Interests, Personal and Institutional, Research Grant, Invited Speaker: Amgen, Roche; Financial Interests, Institutional, Research Grant: Merck, Sanofi, Lilly; Financial Interests, Personal and Institutional, Research Grant, Congress: Servier; Financial Interests, Personal, Advisory Board: Bayer. E.J.T. Österlund: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Institutional, Research Grant, Unrestricted: Amgen, Servier; Financial Interests, Institutional, Research Grant: Roche, Merck, Sanofi; Financial Interests, Personal, Advisory Board: Amgen, Roche, Merck, Sanofi, Servier. A. Uutela: Financial Interests, Institutional, Research Grant: Amgen, Lilly, Merck KGaA, Roche Finland, Sanofi, Servier. P. Halonen: Financial Interests, Institutional, Funding, unrestricted grant: Amgen, Servier; Financial Interests, Institutional, Funding, grant: Roche, Merck, Sanofi, Servier, Lilly. L. Soveri: Financial Interests, Institutional, Research Grant: Amgen, Roche, Merck, Servier, Lilly. H.P. Stedt: Financial Interests, Personal and Institutional, Research Grant, Invited Speaker, Advisory Board: Amgen; Financial Interests, Personal and Institutional, Research Grant, Invited Speaker, Advisory Board, Congress costs: Roche; Financial Interests, Personal and Institutional, Research Grant, Advisory Board: Merck; Financial Interests, Institutional, Research Grant: Sanofi, Servier, Lilly; Financial Interests, Personal, Funding, Congress costs: Bayer; Financial Interests, Personal, Advisory Board: Pierre Fabre, Bristol Myers Squibb. A. Lamminmaki: Financial Interests, Institutional, Research Grant: Amgen, Roche, Merck, Sanofi, Servier, Lilly. S.N.B. Aho: Financial Interests, Institutional, Research Grant, Unrestricted grant: Amgen, Servier; Financial Interests, Institutional, Research Grant: Sanofi, Lilly, Roche Finland, Merck; Financial Interests, Personal, Sponsor/Funding, Attendance fee to WCGC 2020: Roche. T. Muhonen: Financial Interests, Institutional, Research Grant: Amgen, Lilly, Merck, Roche, Sanofi, Servier; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Amgen. A. Algars: Financial Interests, Institutional, Research Grant: Amgen, Roche, Merck, Sanofi, Servier, Lilly; Financial Interests, Personal, Advisory Board: Amgen, Roche, Merck, Sanofi, Bayer, BMS, MSD; Financial Interests, Personal, Invited Speaker: Eisai. E. Heervä: Financial Interests, Personal, Advisory Board: Amgen, Roche, Merck, AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Research Grant: Servier, Lilly. A. Nordin: Financial Interests, Institutional, Research Grant: Amgen, Roche, Merck, Sanofi, Servier, Lilly. L.J. Aroviita: Financial Interests, Institutional, Research Grant: Amgen, Merck, Sanofi, Roche, Servier, Lilly. P. Nyandoto: Financial Interests, Institutional, Research Grant: Amgen , Lilly, Merck, Roche, Sanofi, Servier. J. Kononen: Financial Interests, Institutional, Research Grant: Lilly, Sanofi, Amgen, Roche, Merck; Financial Interests, Personal, Invited Speaker: Janssen. R. Ristamäki: Financial Interests, Institutional, Research Grant: Amgen, Roche, Merck, Sanofi, Servier, Lilly; Financial Interests, Personal, Invited Speaker: Amgen, Merck, Eisai; Financial Interests, Personal, Advisory Board: Roche. H. Isoniemi: Financial Interests, Institutional, Research Grant: Amgen, EliLilly, Merck, Roche, Sanofi, Servier. All other authors have declared no conflicts of interest.