Abstract 72P
Background
Bone mets are frequent in NSCLC. The receptor activator of Nuclear Factor κB (RANK)/ RANKL/osteoprotegerin (OPG) pathway is important in bone mets development. EGFR signaling promotes osteoclast formation and stimulation. Understanding the biological mechanism of bone mets development might have implications for treatment strategies. We studied the association of EGFR, RANKL, RANK, OPG gene expression in tumor and presence of bone mets in mNSCLC.
Methods
Retrospective multicenter study (2008–2017), included: EGFR mutated (EGFR+), Kirsten rat sarcoma (KRAS+), EGFR/KRAS wildtype mNSCLC. Ribonucleic Acid was isolated from tumor samples and EGFR, RANK, RANKL, OPG gene expressions were determined via quantitative Polymerase Chain Reaction. Data on demographics, molecular subtyping, origin of pathology sample, presence/progression of bone mets, SREs were collected. Primary endpoint: relation between EGFR, RANK, RANKL, OPG gene expression, RANKL:OPG ratio and bone mets.
Results
n 169/335 (50%) pts tumor samples were available, in 73 (43%) gene expression analysis could be performed. 46/73 (63%) pts had bone mets at diagnosis/developed bone mets (table). EGFR+ NSCLC had significantly higher EGFR gene expression compared to other tumors. Pts with bone mets had a significantly higher RANKL gene expression and RANKL:OPG ratio compared to those without, but EGFR gene expression was not different. An increased RANKL:OPG ratio resulted in a 1.65x increased risk to develop bone mets, especially in the first 450 days after diagnosis of mNSCLC.
Table: 72PBaseline characteristics
| Characteristics | Total n = 73 |
|---|---|
| Female n (%) | 46 (63) |
| Never smoker n (%) | 8 (11) |
| Mean age at diagnosis metastatic NSCLC, years (range) | 62.8 (32–84) |
| Molecular subgroup n (%) | |
| EGFR+ | 23 (32) |
| KRAS+ | 36 (49) |
| EGFR/KRAS wildtype | 14 (19) |
| Origin of pathology sample n (%) | |
| Lung (primary tumor) | 29 (40) |
| Bone | 9 (12) |
| Other metastasis | 35 (48) |
| Metastatic disease at diagnosis n (%) | 47 (64) |
| Bone mets at diagnosis stage IV n (%) | 27 (37) |
| Bone mets at diagnosis or during course of disease n (%) | 46 (63) |
| SRE n (% of all pts with bone mets) | 26 (57) |
| Type of SRE n (% of all SREs) | |
| Radiotherapy | 25 (96) |
| Pathologic fracture | 4 (15) |
| Surgery | 6 (23) |
| Spinal cord compression | 2 (8) |
| BTA use in all pts n (%) | 9 (12) |
| Denosumab | 1 (1) |
| Bisphosphonate | 8 (11) |
Conclusions
Increased RANKL gene expression and RANKL:OPG ratio, but not EGFR expression, was associated with presence of bone mets. Increased RANKL:OPG gene ratio was associated with a higher incidence of bone mets development.
Legal entity responsible for the study
The authors.
Funding
The Five4Five Foundation, Cancer Research Fund Limburg (2018).
Disclosure
A. Brouns: Financial Interests, Personal, Advisory Board, Not related to the work submitted in the abstract: Janssen. L. Hendriks: Financial Interests, Institutional, Advisory Board: Amgen, Boehringer Ingelheim, Eli Lilly, Novartis, Pfizer, Takeda, BMS, Merck, Janssen, MSD; Financial Interests, Personal, Other, mentorship with key opinion leaders funded by AstraZeneca: AstraZeneca; Financial Interests, Institutional, Invited Speaker, for educational webinar: AstraZeneca, Eli Lilly; Financial Interests, Institutional, Invited Speaker, educational webinar/interview: Bayer; Financial Interests, Institutional, Invited Speaker, educationals: MSD; Financial Interests, Personal, Invited Speaker, for webinars: Medtalks; Financial Interests, Institutional, Advisory Board, one time also personal: Roche; Financial Interests, Institutional, Other, performing interviews at conference: Roche; Financial Interests, Personal, Other, travel support: Roche; Financial Interests, Institutional, Other, podcast on brain metastases: Takeda; Financial Interests, Personal, Invited Speaker, payment for post ASCO round table discussion: VJOncology; Financial Interests, Personal, Invited Speaker, payment for post ASCO/ESMO/WCLC presentations, educational committee member: Benecke; Financial Interests, Institutional, Invited Speaker, payment for post ESMO/ASCO discussion: high5oncology; Financial Interests, Institutional, Other, educational webinar: Janssen; Financial Interests, Personal, Other, member of the committee that revised these guidelines: Dutch guidelines NSCLC, brain metastases and leptomeningeal metastases; Financial Interests, Institutional, Research Grant, for IIS: Roche, Boehringer Ingelheim, AstraZeneca, Takeda; Financial Interests, Institutional, Invited Speaker: AstraZeneca, GSK, Novartis, Merck Serono, Roche, Takeda, Blueprint Medicines, Mirati, AbbVie, MSD, Gilead; Financial Interests, Institutional, Research Grant, donation for health care improvement project: Merck; Financial Interests, Institutional, Research Grant, funding for healthcare improvement project: Pfizer; Non-Financial Interests, Personal, Other, Chair metastatic NSCLC for lung cancer group: EORTC; Non-Financial Interests, Personal, Other, secretary NVALT studies foundation: NVALT. A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Sanofi, Amgen, Bayer, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: Takeda, Eli Lilly, Janssen, Pfizer, AstraZeneca, Eli Lilly, Amgen, Daiichi Sankyo, Roche, JNJ, Mirati; Financial Interests, Institutional, Research Grant: Amgen; Non-Financial Interests, Personal, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Personal, Member: IASCL, ASCO, AACR. All other authors have declared no conflicts of interest.