229P - Clinicopathologic and genomic features of patients with mucinous lung adenocarcinoma and response to systemic therapies

Background

Approximately 10% of lung adenocarcinomas (LUAD) have mucinous features (LUAD^Muc). 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 LUAD^Muc and compared to LUAD without mucinous components (LUAD^Non-muc).

Results

LUAD^Muc represented 9.9% of LUAD (N=406/4,106). Compared to LUAD^Non-muc, patients with LUAD^Muc 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 LUAD^Non-muc, in LUAD^Muc 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 LUAD^Non-muc (N=3,206), LUAD^Muc (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 LUAD^Non-muc (N=1,359), LUAD^Muc (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 LUAD^Non-muc (N=1,064), LUAD^Muc (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 LUAD^Non-muc (N=126), LUAD^Muc (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 LUAD^Non-muc, LUAD^Muc is associated with distinct mutations, a lighter smoking history, lower PD-L1 and TMB. In addition, advanced LUAD^Muc commonly has contralateral lung metastasis and worse outcomes to standard treatments than LUAD^Non-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.