1516P - Lung-only metastatic PDAC: Another disease?

Background

Pancreatic ductal adenocarcinoma (PDAC) prognosis is poor, especially at metastatic stage and metastatic sites are prognosis factors, such as liver that is associated with a poor prognosis. Conversely, a better prognosis has been suggested for lung-only metastases. Main study objectives were to compare overall survival (OS), clinical characteristics and molecular profiles of PDAC patients (pts), depending on their metastatic site.

Methods

A retrospective analysis was performed in single academic-center and included all pts between 2010-2022 with metastatic PDAC. A longitudinal follow-up was performed to account for all disease course. Lung-only pts were defined as pts with only lung metastases all along the disease course. HR and P-value were computed via cox regression between lung-only metastases (lung-mets), liver-only metastases(liver-mets), peritoneal-only metastases (peritoneal-mets) and other metastases (other-mets).

Results

Overall, 961 pts were included, with 48% women. Of them, 551 were metastatic at diagnosis and 410 became metastatic during their disease course. In the whole population, 98 patients had lung-mets (10.2%) with more women (67%) and 438 had liver-mets (45.6%) with less women (39%) (p<0.05). Median OS was significant higher in the lung-mets group with an OS of 38.5 months (mo) [95%CI: 33.1-48.7] (p<0.001) compared to liver-mets (17.2 mo [14.2;18.8], peritoneal-mets (18.9 mo [16.9;24.4]) and other-mets (16.6 mo [13.9;19.1]). Results were similar restricted to pts metastatic at diagnosis. OS was correlated negatively with the number of lung nodes, with an OS of 38.9 mo [31.8;66.5] in the group of pts with ≤ 3 lung-lesions vs 14.6 mo [10.1;20.1] in pts with ≥ 4 lesions. Similar results were observed with the number of liver lesions. Of the 366 pts with contributive molecular profile, most common mutations were KRAS (79.8%), TP53(68.3%), CDKN2A/B (23.5%) and SMAD4 (11.2%). KRAS mutations were over-represented in pts with liver-mets only (87.0%), compared with those with lung-mets only (66.7%) (p<0.05).

Conclusions

Pts with PDAC lung-mets only, had a better OS than other pts, were more frequent in women, and harbored less KRAS mutation. Our results argue in favor of a distinct disease with a better prognosis. Locoregional therapies are currently under investigation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Boileve: Financial Interests, Institutional, Other: Ipsen, Merck, Pfizer. M.P. Ducreux: Financial Interests, Personal, Invited Speaker: Roche, Amgen, Pierre Fabre, Merck KGaA, Pfizer, Bayer, Lilly, Servier, MSD, BeiGene; Financial Interests, Personal, Advisory Board: Roche, Basilea, Pierre Fabre, Boehringer Ingelheim, Rafael, Servier, Zymeworks, Ipsen, Bayer, HalioDX, Lilly, GSK, Daiichi Sankyo, MSD, Servier, BeiGene; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Funding, Partial funding of a trial evaluating the role of bevacizumab in NET: Roche; Financial Interests, Institutional, Funding, Partial funding of a trial evaluating the role of steptozotocin in NET: Keocyt; Financial Interests, Institutional, Local PI: Rafael, Amgen; Financial Interests, Institutional, Funding: Bayer; Other, My wife is head of the oncology business unit in the French Affiliate of Sandoz: Sandoz France. A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, Eisai, BMS; Financial Interests, Personal, Advisory Board: Basilea, Taiho, Relay Therapeutics, QED Therapeutics, Debiopharm, MSD, Boehringer Ingelheim; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Principal Investigator, M19-345; M21-404: AbbVie; Non-Financial Interests, Principal Investigator, CO42216; WP42627; CO40939; GO44479; GO42216: Roche; Non-Financial Interests, Principal Investigator, MCLA-158; MCLA-128: Merus; Non-Financial Interests, Principal Investigator, SGNB6A: Seattle Genetics; Non-Financial Interests, Principal Investigator, TAS-120-202: Taiho; Non-Financial Interests, Principal Investigator, Krystal-10: Mirati; Non-Financial Interests, Principal Investigator, ADP-0033: Adaptimmune; Non-Financial Interests, Principal Investigator, ACT16902: Sanofi; Non-Financial Interests, Principal Investigator, C4201002; SGNB6A: Pfizer; Non-Financial Interests, Principal Investigator, RLY-4008: Relay Therapeutics; Non-Financial Interests, Principal Investigator, CC-90011: Celgene/BMS; Non-Financial Interests, Principal Investigator, Loxo-IDH; Loxo-RAS: Loxo/Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator, SN-201 study: Sotio; Non-Financial Interests, Principal Investigator, Tropics-03: Gilead; Non-Financial Interests, Principal Investigator, BI1403: Boehringer Ingelheim; Non-Financial Interests, Principal Investigator, CA120-1001: BMS. V. Boige: Financial Interests, Personal, Advisory Board: Bayer, Merck Serono, BMS, Roche; Financial Interests, Personal, Invited Speaker: MSD, Ipsen; Financial Interests, Institutional, Funding: Merck Serono. All other authors have declared no conflicts of interest.