Abstract 868: Prediction of clinical benefit to checkpoint blockade in advanced NSCLC patients using radiomics of PET/CT images

(1) Background: The immune checkpoint blockade (ICB) has shown promising efficacy in non-small-cell lung cancer (NSCLC) patients with significant clinical benefits and durable responses, but the overall response rate to ICBs is only 20%. The lack of responsiveness to ICBs is currently a central problem in cancer immunotherapy. (2) Methods: Four public cohorts comprising 2986 patients with NSCLC were included in the study. We screened 158 patients with NSCLC with no durable clinical benefit (NDB) to ICBs in the Rizvi cohort and identified NDB-related gene mutations in these patients using univariate and multivariate Cox regression analyses. Programmed death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB), neoantigen load, tumor-infiltrating lymphocytes, and immune-related gene expression were analyzed for identifying gene mutations. A comprehensive predictive classifier model was also built to evaluate the efficacy of ICB therapy. (3) Results: Mutations in FAT1 and KEAP1 were found to correlate with NDB in patients with NSCLC to ICBs; however, the analysis suggested that only mutation in FAT1 was valuable in predicting the efficacy of ICB therapy, and that mutation in KEAP1 acted as a prognostic but not a predictive biomarker for NSCLC. Mutations in FAT1 were associated with a higher TMB and lower multiple lymphocyte infiltration, including CD8 (T-Cell Surface Glycoprotein CD8)+ T cells. We established a prognostic model according to PD-L1 expression, TMB, smoking status, treatment regimen, treatment type, and FAT1 mutation, which indicated good accuracy by receiver operating characteristic (ROC) analysis (area under the curve (AUC) for 6-months survival: 0.763; AUC for 12-months survival: 0.871). (4) Conclusions: Mutation in FAT1 may be a predictive biomarker in patients with NSCLC who exhibit NDB to ICBs. We proposed an FAT1 mutation-based model for screening more suitable NSCLC patients to receive ICBs that may contribute to individualized immunotherapy.

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Immunotherapy plus chemotherapy showed superior clinical benefit to chemotherapy alone in advanced NSCLC patients after progression on osimertinib

Thoracic Cancer ◽

10.1111/1759-7714.14271 ◽

2021 ◽

Author(s):

Yaping Long ◽

Qi Xiong ◽

Qi Song ◽

Yao Li ◽

Xiaoyan Li ◽

...

Keyword(s):

Clinical Benefit ◽

Advanced Nsclc ◽

Nsclc Patients

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Phase II pharmacodynamic trial of erlotinib in advanced non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy: FISH results

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7160 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7160-7160 ◽

Cited By ~ 2

Author(s):

E. Felip ◽

F. Rojo ◽

M. Reck ◽

A. Heller ◽

B. Klughammer ◽

...

Keyword(s):

Clinical Benefit ◽

Copy Number ◽

Advanced Nsclc ◽

Gene Copy Number ◽

Large Cell ◽

Gene Copy ◽

Egfr Gene ◽

Previously Treated ◽

Never Smokers ◽

Nsclc Patients

7160 Background: The HER1/EGFR inhibitor erlotinib significantly prolongs survival of patients with previously-treated advanced NSCLC. Methods for selecting patients most likely to derive clinical benefit from erlotinib are not established. Increased HER1/EGFR gene copy number has been suggested as a potential predictive biomarker of clinical benefit, and was investigated in this phase II study. Methods: Advanced NSCLC patients who failed first line chemotherapy were treated with erlotinib monotherapy, 150 mg/d p.o. Each patient underwent tumor biopsy before start of treatment. Tumor HER1/EGFR gene amplification status was assessed using FISH, and classified as positive (amplification, polysomy, high polysomy) or negative (disomy, trisomy). Results: 83 patients were included: median age 56 (range 35–78); sex: male 72%, female 28%; histology: adenocarcinoma 43%, large cell 31%, squamous cell 19%, others 7%; smoking status: 44 current smokers, 28 former smokers, 11 never smokers. Of 73 evaluable patients, 7 (10%) achieved partial response (PR), 28 (38%) had stable disease (SD) and 38 (52%) had disease progression. PRs were observed in 4 males / 3 females; in 5 adenocarcinomas / 1 large cell/ 1 squamous cell; in 2 current / 3 former / 2 never smokers. Erlotinib was well tolerated and no unexpected toxicities were seen. HER1/EGFR gene copy number was evaluated in 53 patients. 15 patients were FISH +, 10 of whom achieved clinical benefit (PR, or SD for ≥12 weeks). Only 5 of 38 FISH - patients had clinical benefit. FISH + patients achieved a longer median time to progression (137 vs 43 days; p = 0.00011; HR 0.35) as well as overall survival (226 vs 115 days; p = 0.3221, HR 0.722). Conclusion: In this study, increased HER1/EGFR gene copy number was associated with a better outcome on erlotinib therapy. [Table: see text] [Table: see text]

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Association of the Metabolic Score Using Baseline FDG-PET/CT and dNLR with Immunotherapy Outcomes in Advanced NSCLC Patients Treated with First-Line Pembrolizumab

Cancers ◽

10.3390/cancers12082234 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2234 ◽

Cited By ~ 2

Author(s):

Romain-David Seban ◽

Jean-Baptiste Assié ◽

Etienne Giroux-Leprieur ◽

Marie-Ange Massiani ◽

Michael Soussan ◽

...

Keyword(s):

Fdg Pet ◽

Advanced Nsclc ◽

Group Versus ◽

Progression Free Survival ◽

Metabolic Tumor Volume ◽

First Line ◽

Good Group ◽

Pet Ct ◽

Fdg Pet Ct ◽

Nsclc Patients

Background: We aimed to assess the clinical utility of a previously published score combining the total metabolic tumor volume (TMTV) on baseline FDG-PET/CT and pretreatment derived from the neutrophils to lymphocytes ratio (dNLR) for prognostication in NSCLC patients undergoing first-line immunotherapy (IT). Methods: In this multicenter retrospective study, 63 advanced NSCLC patients with a PD-L1 tumor proportion score (TPS) ≥50%, who underwent FDG-PET/CT before first-line IT, treated from January 2017 to September 2019, were enrolled. Associations between this score and the progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and overall response rate (ORR) were evaluated. Results: The median (m) PFS and mOS were 7.7 (95% CI 4.9–10.6) and 12.1 (8.6–15.6) months, respectively, and DCR and ORR were 65% and 58%, respectively. mOS was 17.9 months (14.6 not reached) for the good group versus 13.8 (95%CI 8.4–18.9) and 6.6 (CI 2.0–11.2) months for the intermediate and poor groups, respectively. mPFS was 15.1 (95%CI 12.1–20.0) months for the good group versus 5.2 (1.9–8.5) and 1.9 (95%CI 1.3–2.5) months for the intermediate and poor groups, respectively. The poor prognosis group was associated with DCR and ORR (p < 0.05). Conclusions: The metabolic score combining TMTV on the baseline FDG-PET/CT scan and pretreatment dNLR was associated with the survival and response in a cohort of advanced NSCLC patients with ≥50% PD-L1 receiving frontline IT.

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