ICBs are today the backbone of non-oncogene addicted NSCLC, both alone and in combination with chemotherapy (CT-ICB). To date, PD-L1 is the only predictive factor for ICBs benefit. Tumor burden is a new emerging additional biomarker to select pts who may derive a benefit from a CT combination compared to single agent ICBs. The biological correlates of tumor burden are largely unknown.
In this multicentric study, 18F FDG PET scans were performed ≤ 42 days from 1st line initiation (CT, ICBs or CT-ICB). Total MTV was calculated with a threshold of 42% of SUV max. Progression Free Survival (PFS) and Overall Survival (OS) were analyzed with Kaplan Meyer method and log rank test. On a subset of pts with PET performed within 30 days from biopsy, transcriptomic data on fresh frozen tissue were correlated with MTV of the biopsied lesion.
488 pts were enrolled, 162 treated with ICBs, 232 with CT-ICB and 94 with CT. The 3 groups were comparable in terms of MTV, sex, stage and PS, pts in ICBs are older (69y vs 64 for CT-ICB and 62 for CT). MTV was negatively correlated with the outcome of ICI, with a median PFS of 31.8 months for 1st quartile (1Q), 13.8 for 2Q, 4.7 for the 3Q and 1.8 for the 4Q (p < 0.001). A weaker correlation was found for CT-ICB, with a median PFS of 14.0m 1Q, 7.1 for 2Q, 7.0 for 3Q and 5.5 for 4Q (any PD-L1 expression), p 0.037, No correlation was found for CT ( p 0.696). When comparing ICI to CT-ICB in patients with PD-L1 ≥ 50%, an advantage in PFS was seen for CT-ICB (10.7 vs 3.0m, p 0.039 ) for pts with MTV > median (100cc) as well as in 3 (73% vs 92%, p 0.043) and 6 months OS (66 vs 89%, p 0.033), but not in those with MTV < median. Transcriptome analysis was performed on 48 pts and showed a negative correlation of MTV with GSEA immune signatures, as well as with RNAseq immune infiltrate quantification (Cybersort, p 0.016).
MTV identifies NSCLC pts with a worse prognosis and an increased rate of early progression and death on ICB. In the subgroups of PD-L1≥50%, pts with high MTV may do better on CT-ICB compared to ICB. Transcriptomic analysis suggests that tumor microenvironment become increasingly immune suppressive with the increase in volume.
The authors.
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G. Zalcman: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, AstraZeneca, Pfizer, Boehringer Ingelheim; Non-Financial Interests, Personal, Invited Speaker: Roche-France, Bristol Myers Squibb, Takeda. J. Remon Masip: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, MSD, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Jansse, Takeda, Sanofi; Financial Interests, Personal, Expert Testimony: OSE Immunotherapeutics; Non-Financial Interests, Personal, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD; Non-Financial Interests, Personal, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca. L. Hendriks: Financial Interests, Institutional, Advisory Board: Amgen, Boehringer Ingelheim, Lilly, Novartis, Pfizer, Takeda, BMS, Merck, Janssen, MSD; Financial Interests, Personal, Other, mentorship with key opinion leaders funded by AstraZeneca: AstraZeneca; Financial Interests, Institutional, Invited Speaker, for educational webinar: AstraZeneca, Lilly; Financial Interests, Institutional, Invited Speaker, educational webinar/interview: Bayer; Financial Interests, Institutional, Invited Speaker, educationals: MSD; Financial Interests, Personal, Invited Speaker, for webinars: Medtalks; Financial Interests, Institutional, Advisory Board, one time also personal: Roche; Financial Interests, Institutional, Other, performing interviews at conference: Roche; Financial Interests, Personal, Other, travel support: Roche; Financial Interests, Institutional, Other, podcast on brain metastases: Takeda; Financial Interests, Personal, Invited Speaker, payment for post ASCO round table discussion: VJOncology; Financial Interests, Personal, Invited Speaker, payment for post ASCO/ESMO/WCLC presentations, educational committee member: Benecke; Financial Interests, Institutional, Invited Speaker, payment for post ESMO/ASCO discussion: high5oncology; Financial Interests, Institutional, Other, educational webinar: Janssen; Financial Interests, Personal, Other, member of the committee that revised these guidelines: Dutch guidelines NSCLC, brain metastases and leptomeningeal metastases; Financial Interests, Institutional, Research Grant, for IIS: Roche, Boehringer Ingelheim, AstraZeneca, Takeda; Financial Interests, Institutional, Invited Speaker: AstraZeneca, GSK, Novartis, Merck Serono, Roche, Takeda, Blueprint Medicines, Mirati, AbbVie, MSD, Gilead; Financial Interests, Institutional, Other, drug support for IIS (contract in negotiation): Beigene; Non-Financial Interests, Personal, Other, Chair metastatic NSCLC for lung cancer group: EORTC; Non-Financial Interests, Personal, Other, secretary NVALT studies foundation: NVALT. C. Helissey: Financial Interests, Personal, Invited Speaker: Janssens, Roche, Astellas, AstraZeneca, Sanofi; Non-Financial Interests, Personal, Principal Investigator: Janssen, Sanofi, Roche, Astellas. I. Monnet: Other, Personal, Other, invitation to virtual ASCO 2021 and 2022: Pfizer; Other, Personal, Other, invitation to ESMO congress 2021 and 2022: Takeda. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Personal, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Personal, Principal Investigator: AbbVie, Sanofi, Janssen. F. Barlesi: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi Aventis, Seattle Genetics, Takeda; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd. 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: Genzyme Corporation, Chugai pharmaceutical, Eisai, Inivata, Ipsen, Turning Point Therapeutics. All other authors have declared no conflicts of interest.