606P - Regional lymph nodes (N+ vs N0) in metastatic colorectal cancer

Background

Regional lymph node metastases are negative prognostic factors in localized disease and after liver resection, but little is known in metastatic colorectal cancer (mCRC). We studied demographics, treatments, and outcomes for mCRC with (N+) and without (N0) regional lymph node metastases in population-based and real-world settings.

Methods

Patients from three Nordic mCRC cohorts were combined; the population based PRCRC-study, the likewise Uppsala Region cohort and the real-world RAXO study. The dataset included 1764 patients with resected primary tumours, of which 1710 had pathologic N-stage reported. Characteristics and treatments were compared using Chi-square. Overall survival (OS) was estimated with Kaplan-Meier and compared using log-rank.

Results

N+ were seen in 1242 (73%) and N0 in 468 (27%). N+ patients associated with female sex, right-sided primaries, higher tumour grade, synchronous metastases, more metastatic sites, more liver, distant lymph node, and peritoneal metastases, and fewer lung metastases compared with N0 (Table). No differences were seen for ECOG and age >70 years. BRAF-V600E mutations (mt) were more common in N+, as was deficient mismatch repair, whereas RASmt were seen less often.

Table: 606P

N+ patients had less metastasectomies (31% vs 39%, p=0.001) and more systemic therapy only (51% vs 43 %, p=0.001), with no difference for best supportive care. Median OS was shorter in the N+ vs N0 group (23 vs 34 months, p <0.001); likewise for metastasectomy patients (64 vs 96 months, p=0.001), and systemic therapy only (20 vs 27 months, p=0.001). N+ did worse than N0 with non-liver metastasectomy (77 vs 45 months, p=0.018), with similar trends for synchronous (77 vs 39 months, p=0.060) and metachronous presentation (not reached vs 58 months, p=0.172) subgroups.

Conclusions

Regional lymph node metastases (N+) were associated with several other negative prognostic factors. This resulted in fewer metastasectomies and impaired outcome in all and non-liver metastasectomy and systemic therapy only.

Clinical trial identification

NCT01531595; EudraCT 2011-003137-33.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The PRCRC-study was supported by The Norwegian, Danish, and Swedish Cancer Societies. Amgen partly supported the NGS analysis performed in patients included in the Uppsala region cohort. The RAXO-study was supported by Finska Läkaresällskapet, Cancer Foundation Finland, Relander’s Foundation , the Competitive State Research Financing of the Expert Responsibility Area of Tampere, Helsinki and Turku, Tampere University Hospital Funds, the Research Fund of Helsinki University Hospital. The infrastructure with database and study nurses were partly supported by pharmaceutical companies (Amgen unrestricted grant 2012–2020, Eli Lilly 2012–2017, Merck KGaA 2012–2020, Roche Oy 2012–2020, Sanofi 2012–2017 and Servier unrestricted grant 2016–2020). The funding sources had no role in the design and conduct of the study, collection, analysis and interpretation of the data, or decision to submit the manuscript for publication.

Disclosure

E. Osterlund: Financial Interests, Personal, Invited Speaker, Advisory board: Amgen; Financial Interests, Institutional, Research Grant, PI's institution: Amgen, Roche, Servier; Financial Interests, Institutional, Research Funding, PI's institution: Eli Lilly, Merck, Sanofi; Non-Financial Interests, Personal, Advisory Board: Merck, Servier; Financial Interests, Personal, Advisory Board: Roche. H. Isoniemi: Financial Interests, Institutional, Research Funding: Amgen, Servier, Sanofi, Roche, Merck, Eli Lilly and Company; Non-Financial Interests, Personal, Advisory Board: Servier. H. Sorbye: Financial Interests, Personal, Invited Speaker: Ipsen, SAM Nordic, Pierre Fabre; Financial Interests, Personal, Advisory Board: AAA; Non-Financial Interests, Principal Investigator: Bristol Myers Squibb. P. Pfeiffer: Financial Interests, Local PI: Sanofi-Aventis, Eli Lilly, Nordic Drug, MSD, Celgene, Servier, Roche, AstraZeneca, Taiho, Shire, Isofol, Pierre Fabre, Scandion, GSK, Amgen, Merck, Boehringer Ingelheim, Pfizer, Bristol Myers Squibb, Eisai, Astellas; Financial Interests, Personal, Local PI: Egetis. P. Halonen: Financial Interests, Institutional, Research Grant: Amgen. A. Uutela: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Institutional, Research Grant: Amgen, Eli Lilly, Merck; Financial Interests, Institutional, Research Funding: Roche, Sanofi; Financial Interests, Personal, Research Funding: Servier. T. Salminen: Financial Interests, Personal, Advisory Board: Amgen, Roche, Servier; Financial Interests, Institutional, Research Grant: Amgen, Eli Lilly, Merck; Financial Interests, Institutional, Research Funding: Roche, Sanofi, Servier. A. Algars: Financial Interests, Personal, Advisory Board: Amgen, Merck, Roche; Financial Interests, Institutional, Advisory Board, PI:s institution: Amgen, Eli Lilly; Financial Interests, Institutional, Research Grant, PI:s institution: Merck, Sanofi, Servier; Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Personal, Advisory Board: Servier. R. Ristamaki: Financial Interests, Institutional, Research Grant, PI's institution: Amgen; Financial Interests, Institutional, Research Funding, PI's institution: Eli Lilly, Merck, Roche, Sanofi, Servier; Financial Interests, Personal, Advisory Board: Amgen, Merck, Roche, AstraZeneca. R. Kallio: Financial Interests, Personal, Advisory Board: Amgen, Roche, Merck, Sanofi, Servier. A. Lamminmäki: Financial Interests, Personal, Advisory Board: Amgen, Merck, Roche, Servier; Financial Interests, Institutional, Research Grant: Amgen, Eli Lilly, Merck, Roche; Financial Interests, Institutional, Research Funding: Sanofi, Servier. A. Ristimäki: Financial Interests, Personal, Advisory Board: Amgen, Eli Lilly, Merck, Roche, Sanofi, Servier. L. Nieminen: 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. J. Sundström: Financial Interests, Institutional, Research Grant, PI's institution: Amgen, Eli Lilly, Servier; Financial Interests, Institutional, Research Funding, PI's institution: Merck, Roche, Sanofi; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Training: Ipsen. M.J. Mäkinen: Financial Interests, Personal, Advisory Board: Amgen, Merck, Roche, Servier; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb. S. Kytölä: Financial Interests, Institutional, Research Grant, PI's institution: Amgen, Servier; Financial Interests, Institutional, Research Funding, PI's institution: Eli Lilly, Merck, Roche, Sanofi; Financial Interests, Personal, Invited Speaker: Roche, Lilly, Amgen, Novartis. B. Glimelius: Financial Interests, Institutional, Research Grant: Amgen. 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. All other authors have declared no conflicts of interest.