1456P - Exploring biological and molecular factors as outcome predictors for pembrolizumab (Pem) or pembrolizumab-chemotherapy (Pem-CT) in advanced non-small cell lung cancer (NSCLC)

Background

Pem and Pem-CT are first-line treatments for non-oncogene addicted NSCLC, but no validated predictors of benefit beyond PD-L1 are available. We explored the impact of biological or molecular factors on outcomes with Pem or Pem-CT.

Methods

We retrospectively collected data from patients (pts) treated with Pem or Pem-CT in three European centers. We categorized NLR and LDH into good, intermediate, and poor groups based on none, one, or both NLR≥3 and LDH>upper limit of normal. Molecular profiles at baseline were obtained from tissue or blood samples, with varying techniques and panels among and within centers. We used multivariable Cox regression models to explore prognostic impact of NLR-LDH categories, differential efficacy of the treatments in the categories and in KRAS-mutant (mut) tumors. We adjusted for center and known prognostic factors (age, gender, PS ECOG, number of metastatic sites, brain and liver metastases), included if associated with progression free survival (PFS) and/or overall survival (OS) with a p<0.05 in univariate Cox models.

Results

We included 440 pts, 224 treated with Pem and 216 with Pem-CT. Pem population was older (p<0.0001), but the groups were balanced for other prognostic factors. At a median (m) follow up of 16.3 and 12.9 months for Pem and Pem-CT group, mPFS and mOS were 7.6 and 15.9 months; 7.2 and 22.8 months, respectively. The combination of baseline NLR-LDH was prognostic for both Pem and Pem-CT (Table). No statistically significant difference between the treatments was seen in the subgroups. 159 (36%) tumors were KRAS-mut. In KRAS-mut tumors no difference was seen between the two treatments neither in PFS (p= 0.55) nor OS (p=0.79). Table: 1456P

Conclusions

Combining baseline NLR and LDH provides a prognostic stratification, regardless of the addition of CT to Pem as first-line treatment. No difference between the two strategies was seen in the KRAS-mut tumors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Italian Ministry of Health; Fondazione Compagnia di San Paolo.

Disclosure

M. Aldea: Financial Interests, Institutional, Advisory Role: Viatris; Financial Interests, Institutional, Other, travel grants: Sandoz. G. Barletta: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca, GSK; Financial Interests, Institutional, Other, honoraria: Roche, Pierre Fabre. C. Dellepiane: Financial Interests, Institutional, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Roche; Financial Interests, Institutional, Other, travel and attending meetings support: Sanofi, Amgen, Merck Sharp and Dohme. G. Rossi: Financial Interests, Institutional, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Merck, Sharp & Dohme, Janssen, Roche, Novartis; Other, Institutional, Other, Consultant: AstraZeneca; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Takeda, Italfarmaco. L. Del Mastro: Financial Interests, Personal, Invited Speaker, Educational meeting: Novartis, Symposia, Andromeda E20, Vyvamed srl; Financial Interests, Personal, Invited Speaker, Lecture: Ipsen; Financial Interests, Personal, Advisory Board, Her2+ and TN breast cancer: Roche; Financial Interests, Personal, Writing Engagement, Consultancy for TNBC text: Roche; Financial Interests, Personal, Advisory Board, denosumab: Amgen; Financial Interests, Personal, Advisory Board, Early and metastatic BC: Eli Lilly; Financial Interests, Personal, Invited Speaker, CDK4-6 inhibitors: Eli Lilly; Financial Interests, Personal, Advisory Board, tucatinib: Seagen Int; Financial Interests, Personal, Advisory Board, Oncotype dx: Exact sciences, Havas life; Financial Interests, Personal, Advisory Board, Neratinib: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Internal training: MSD; Financial Interests, Personal, Invited Speaker, Educational meetings: Accademia Nazionale Medicina; Financial Interests, Personal, Writing Engagement, Author for BC text: Pensiero Scientifico Editore; Financial Interests, Personal, Advisory Board, Breast cancer: Uvet; Financial Interests, Personal, Other, Author slide kits and interviews: Think2it; Financial Interests, Personal, Advisory Board, Palbociclib: Pfizer; Financial Interests, Personal, Invited Speaker, Breast cancer: Aristea, Meeting SrL; Financial Interests, Personal, Other, Author slide kits: Forum service; Financial Interests, Personal, Other, Author text about biosimilars: Edizioni Minerva Medica; Financial Interests, Personal, Other, consultant: Kardo srl; Financial Interests, Personal, Invited Speaker, Breast cancer meetings: Delphi international, Over srl; Financial Interests, Personal, Invited Speaker: Prex Srl, Editree; Financial Interests, Personal, Advisory Board: Uvet, Collage SpA, Daiichi Sankyo, AstraZeneca, Agendia, Gilead; Financial Interests, Personal, Other, Interview: Infomedica srl; Financial Interests, Personal, Other, Consultant: Sharing progress in cancer care - Switzerland; Financial Interests, Personal, Other, Consultancy: Eli Lilly; Financial Interests, Institutional, Funding, National coordinating PI: Roche; Financial Interests, Institutional, Funding, Local PI: AstraZeneca, Roche, Eli Lilly, Daiichi Sankyo, Novella Clinical, Novartis; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. R. Berardi: Financial Interests, Advisory Board: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eisai, Novartis, Merck Sharp and Dhome, Otsuka, Eli Lilly, Pierre Fabre, Italfarmaco, GSK, Incyte, Seagen, Roche. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, Eisai, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. C. Genova: Financial Interests, Personal, Invited Speaker, Speaker's Bureau (scientific meeting): AstraZeneca, Bristol Myers Squibb, Merck-Sharp-Dohme, Eli Lilly, Novartis; Financial Interests, Personal, Advisory Board, Advisory board: Amgen, Sanofi; Financial Interests, Personal, Advisory Board, Advisory Board: Roche, Takeda; Financial Interests, Institutional, Funding, Funding for support of translational study: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Funding in support of translational study: AstraZeneca; Financial Interests, Institutional, Research Grant, Research Grant for translational study: Italian Ministry of Health; Non-Financial Interests, Principal Investigator, Local PI for clinical trials: AstraZeneca, Roche; Non-Financial Interests, Member, Scientific society membership: ASCO, AIOM, FONICAP, AIOT, IASLC, ISLB. All other authors have declared no conflicts of interest.