Abstract 229P
Background
Approximately 10% of lung adenocarcinomas (LUAD) have mucinous features (LUADMuc). The efficacy of immune checkpoint inhibitors (ICI) and KRAS inhibitors for these patients is undefined.
Methods
Clinicopathologic, genomic, and outcomes data were abstracted from patients with LUAD at three academic centers. LUAD with any mucinous component as assessed by a thoracic pathologist was classified as LUADMuc and compared to LUAD without mucinous components (LUADNon-muc).
Results
LUADMuc represented 9.9% of LUAD (N=406/4,106). Compared to LUADNon-muc, patients with LUADMuc had lower tobacco use history (median pack-years: 15 vs 20, P=0.002) and PD-L1 tumor proportion score (median: 0% vs 5%, P<0.0001). At stage IV diagnosis, compared to LUADNon-muc, in LUADMuc contralateral lung metastasis were more frequent (50% vs 39%, P=0.02) and brain metastases were less frequent (30% vs 43%, P=0.02). Among 3,577 patients with genomic profiling, compared to LUADNon-muc (N=3,206), LUADMuc (N=371) had a lower tumor mutational burden (TMB) (median: 6.8 vs 8.5 mut/Mb, P<0.001), a higher prevalence of KRAS, STK11, SMARCA4, NKX2-1, and GNAS mutations, and a lower prevalence of TP53, EGFR, and BRAF mutations (q<0.05). Among patients who received ICIs for advanced disease, compared with LUADNon-muc (N=1,359), LUADMuc (N=96) cases had a lower objective response rate (ORR 10% vs 25%, P<0.001), shorter median progression-free survival (mPFS 2.6 vs 4.0 months, P<0.001) and median overall survival (mOS 10.9 vs 18.1 months, P<0.001). Among patients who received chemo-immmunotherapy, compared with LUADNon-muc (N=1,064), LUADMuc (N=122) had lower ORR (24% vs 38%, P=0.002), shorter mPFS (5.1 vs 7.1 months, P<0.001) and mOS (11.9 vs 20.2 months, P<0.001). Among KRAS G12C-mutated patients who received KRAS inhibitors, compared to LUADNon-muc (N=126), LUADMuc (N=12) had similar ORR (17% vs 36%, P=0.17) and mPFS (4.6 vs 5.7 months, P=0.31), but shorter mOS (7.3 vs 13 months, P=0.04).
Conclusions
Compared to LUADNon-muc, LUADMuc is associated with distinct mutations, a lighter smoking history, lower PD-L1 and TMB. In addition, advanced LUADMuc commonly has contralateral lung metastasis and worse outcomes to standard treatments than LUADNon-muc.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Di Federico: Financial Interests, Personal, Advisory Board: Hanson-Wade; Non-Financial Interests, Personal, Other, Honoraria: Society for Immunotherapy of Cancer. B. Ricciuti: Financial Interests, Personal, Advisory Board: Regeneron, AstraZeneca, Amgen; Financial Interests, Personal, Sponsor/Funding: Regeneron, Genentech, BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Targeted Oncology. J. Alessi: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS; Financial Interests, Personal, Other, Consultant: MSD; Financial Interests, Personal, Other, Consultant: Janssen. J. Zhang: Financial Interests, Personal, Research Grant: Merck, Novartis, Johnson and Johnson; Financial Interests, Personal, Other, personal fees: BMS, AstraZeneca, Novartis, Johnson and Johnson, Geneplus, Hengrui, Innovent. D. Gibbons: Financial Interests, Personal, Advisory Board: Sanofi, GSK, Janssen Research & Development, Ribon Therapeutics, Mitobridge, Eli Lilly, Menarini, Napa Therapeutics; Financial Interests, Personal, Research Grant: Janssen Research & Development, Takeda, AstraZeneca, Mitobridge, Ribon Therapeutics, NGM Biopharmaceuticals, Boehringer Ingelheim, Mirati Therapeutics. J. Heymach: Financial Interests, Personal, Advisory Board: Genentech, Mirati Therapeutics, Eli Lilly & Co., Janssen Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Regeneron, Takeda Pharmaceuticals, BerGenBio, Jazz Pharmaceuticals, Curio Science, Novartis, AstraZeneca, BioAlta, Sanofi, Spectrum Pharmaceuticals, GSK; Financial Interests, Personal, Full or part-time Employment: MD Anderson Cancer Center; Financial Interests, Personal, Invited Speaker: Spectrum; Financial Interests, Institutional, Other, International PI for clinical trials: AstraZeneca; Financial Interests, Institutional, Other, International PI for two clinical trials: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Other, Developed a drug: Spectrum; Financial Interests, Institutional, Invited Speaker: Takeda. M. Nishino: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: Canon Medical Systems, AstraZeneca, Daiichi Sankyo, Konica-Minolta. L. Sholl: Financial Interests, Institutional, Advisory Board: genentech, Lilly, AstraZeneca; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Personal and Institutional, Research Grant: BMS. M. Awad: Financial Interests, Personal, Advisory Board: Merck, Pfizer, BMS, foundation medicine, Novartis, Gritstone bio, Mirati therapeutics, EMD seron, AstraZeneca, Instill bio, regeneron, Janssen, Affini-T Therapeutics; Financial Interests, Institutional, Research Grant: Genentech/Roche, Lilly, AstraZeneca, BMS, Amgen; Financial Interests, Personal, Sponsor/Funding: BMS. K.C. Arbour: Financial Interests, Personal, Advisory Board: G1 Therapeutics, Novartis, Sanofi-Genzyme; Financial Interests, Institutional, Invited Speaker: Revolution Medicines, Mirati, Genentech. A. Schoenfeld: Financial Interests, Personal, Other, Consulting: Johnson and Johnson, KSQ Therapeutics, Perceptive Advisors, Legend Biotech, Iovance Biotherapeutics, Oppenheimer and Co; Financial Interests, Personal, Advisory Board: BMS, Enara Bio, Umoja Biopharma, Prelude Therapeutics, Immunocore, Amgen, Lyell Immunopharma, Heat Biologics; Financial Interests, Personal and Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Iovance Biotherapeutics, GSK, Achilles Therapeutics, BMS, Obsidian; Financial Interests, Personal, Invited Speaker: Synthekine; Non-Financial Interests, Personal, Principal Investigator: GSK, Achilles Therapeutics, Iovance Therapeutics, BMS, Merck, PACT pharma. N. Vokes: Financial Interests, Personal, Advisory Board: Sanofi, oncocyte, Lilly, Regeneron, Amgen, Xencor, AstraZeneca, tempus; Financial Interests, Personal, Sponsor/Funding: Regeneron; Financial Interests, Institutional, Research Grant: Circulogene. J. Luo: Financial Interests, Personal, Other, honoraria: Targeted Oncology, Physicians Education Resource, VJ Oncology, Cancer GRACE, Community Cancer Education Inc; Financial Interests, Personal, Advisory Board: AstraZeneca, Astellas, Amgen, Erasca, Genentech, Kronos Bio, Novartis, Revolution Medicines; Financial Interests, Personal, Other, personal fees: Erasca, Blueprint Medicines, Daiichi Sankyo. All other authors have declared no conflicts of interest.