Abstract 1294P
Background
Pembrolizumab (P) is one of the standard options in untreated non-oncogene addicted NSCLC, either alone when PD-L1 ≥ 50%, or combined with chemotherapy (CT) independently on PD-L1 expression. Biomarkers to select the best strategy are urgently needed. We evaluated the prognostic significance of 18F-FDG PET -derived parameters as well as their potential systemic biological-immunological correlates as biomarkers.
Methods
In this monocentric, retrospective cohort study, we selected all the pts treated with frontline P alone (IO group) or in combination with CT (CT-IO group) with a 18F-FDG PET scan done within 6 weeks before treatment start. Metabolic tumor volume (MTV, defined as tumor volume with ≥ 42% of the SUVmax), total lesions glycolysis (TLG, defined as MTV x SUVmax ), speen/liver ratio (SLR, SUVmean spleen / SUVmean liver) were calculated. Senescent immune phenotype (SIP+) was defined by ≥ 39.5% of CD28-, CD57+, KLRG1+ among CD8+ circulating T cells analyzed by cytofluorometry.
Results
85 pts were enrolled, 44 treated with IO and 41 with CT-IO. 71 (84%) were adenocarcinoma, 48 (56%) were male. Median follow up was 18.8 months for IO and 8.0 for CT-IO. MTV was correlated with inflammatory blood markers such as LDH (p 0.003), C-reactive protein (p 0.016) and derived neutrophil/lymphocyte ratio (dNLR) (p 0.011). MTVlog (HR 4.39, 95% CI 1.41 - 13.67, p 0.011) and SLR (HR 3748.45, 95% CI 19.36 - 725662.8, p 0.002) were negatively correlated with overall survival (OS) in pts treated with IO. Instead, they were not in pts treated with CT-IO (p 0.270 and 0.312 respectively ). Median OS was NR (95% CI NR – NR) in IO pts with MTV < median vs 10.5 (95% CI 2.2-18.8) in IO pts with TMV > median. MTV in IO group remained correlated with OS in multivariate analysis including LDH, dNLR, ECOG PS and liver/bone metastasis. In pts with SIP+ status (n=28), MTV tended to be higher (median 294.5 vs 100 cm3, p 0.067).
Conclusions
PET scan derived parameters (high MTV and high SLR) were correlated with worse outcomes when pts were treated with IO but not with CT-IO. High MTV is correlated with markers of inflammation and possibly with SIP. A larger dataset, including a third cohort of pts treated with chemotherapy alone, will be presented.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Caramella: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche. N. Chaput: Financial Interests, Institutional, Research Grant: BMS Foundation, Sanofi, GSK, Roche, and BMS Foundation; Financial Interests, Personal and Institutional, Other: AstraZeneca; Financial Interests, Personal and Institutional, Other: Cytune Pharma (BSA). A. Marabelle: Financial Interests, Personal, Advisory Board: Merck Serono, BMS, Symphogen/Servier, GSK, Pfizer, Roche/Genentech, OSE immunotherapeutics, Merck (MSD), Sanofi, Pierre Fabre, Imcheck, Johnson & Johnson; Financial Interests, Personal, Invited Speaker: Roche/Genentech, BMS, Merck (MSD), Merck Serono, AstraZeneca/MedImmune, Amgen, Sanofi; Financial Interests, Personal, Advisory Role: Roche, Pierre Fabre, Sanofi, Imcheck, Servier; Financial Interests, Institutional, Research Grant: Merus, BMS, Boehringer Ingelheim, Transgene, Fondation MSD Avenir. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Samsung; Financial Interests, Personal, Other: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Samsung; Financial Interests, Institutional, Principal Investigator: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. F. Barlesi: Financial Interests, Personal, Other: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd., Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda. J-C. Soria: Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Personal, Member of the Board of Directors: Hookipa Pharmaceutical; Financial Interests, Personal, Full or part-time Employment: AstraZeneca from September 2017 to December 2019. B. Besse: Financial Interests, Institutional, Funding: AbbVie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, Ipsen, Merck, MSD, Nektar, Onxeo, Pfizer, PharmaMar, Sanofi, Spectrum Pharmaceuticals, Takeda and Tiziana Pharm 4D Pharma, AbbVie, Amgen, Aptitude Health, Astr. All other authors have declared no conflicts of interest.