Abstract 3964
Background
Immune checkpoint inhibitors (CPI) have revolutionised the treatment of solid tumours with durable responses in cancers with previously limited treatment options. Despite significant improvements in overall survival for some patients(pt), identifying biomarkers to select a population most likely to benefit from CPIs remains challenging.
Methods
We characterized fresh tumour biopsies from 82 pts with metastatic cancer through the Personalised OncoGenomics (POG) program at BC Cancer using whole genome (80X tumour, 40X normal) and transcriptome analysis (WGTA). Subsequently pts were treated with a CPI as part of their standard cancer care. Baseline characteristics and follow up data were collected retrospectively. Durable clinical benefit (DCB) was defined as > 6 months(m) without disease progression and overall survival (OS) from date of first CPI treatment to death.
Results
The 82 pts (59% female) biopsied comprised a heterogeneous cohort: non-small cell lung cancer (30%), breast (17%) and colorectal cancer (13%) were most common, and most patients (45%) had received 1-2 prior treatments. 17 patients (21%) had a DCB and the median follow-up from first dose CPI was 9.2m. Higher tumour mutation burden (>10mut/Mb exome) was predictive of a longer median time to progression/death (TTPD) (5.9 vs 2.6m, p = 0.0055, HR = 0.44) and OS (14.6 vs 7.9m, p = 0.039, HR = 0.52). A higher predicted CD8+ T cell score (CIBERSORT) also predicted for a prolonged median TTPD (3.4 vs 2.4 m, p = 0.0094, HR = 0.51) and OS (12.9 vs 5.3m, p = 0.0014, HR = 0.42). In contrast, patients with PD-L1 expression > 80th percentile did not have a significantly different TTPD or OS. In addition to characterizing individual biomarkers, we note that patients with combinations of markers, particularly high TMB and CD8+ T cell scores, have a further improvement in median TTPD (5.9 vs 2.4m, p = 0.013) and OS (14.5 vs 5.4m, p = 0.014).
Conclusions
The complexity of interpreting the tumour-immune interface to predict CPI efficacy remains challenging, but WGTA allows for identification of combination biomarkers that may help to identify responders. The presence of two or more biomarkers predicted for CPI response in this patient cohort and may more successfully identify these patients in prospective studies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
BC Cancer Foundation.
Disclosure
J. Lavoie: Research grant / Funding (self): University of British Columbia. S. Yip: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Bayer. D. Renouf: Honoraria (self): Celgene; Honoraria (self): Servier; Honoraria (self): Taiho; Honoraria (self): Ipsen; Honoraria (self), Research grant / Funding (institution): Bayer. J.J. Laskin: Honoraria (self), Research grant / Funding (institution): Roche Canada; Honoraria (self): BI Canada; Honoraria (self), Research grant / Funding (institution): AstraZeneca Canada; Research grant / Funding (institution): Pfizer Canada. All other authors have declared no conflicts of interest.
Resources from the same session
1291 - PD-L1 expression in uncommon EGFR-mutant non-small cell lung cancer and its response to immunotherapy
Presenter: Yun Fan
Session: Poster Display session 3
Resources:
Abstract
2171 - CCND1 Amplification Contributes to Immunosuppression in Head and Neck Squamous Cell Carcinoma and the Association with a Poor Response to Immune Checkpoint Inhibitors
Presenter: Chloe Huang
Session: Poster Display session 3
Resources:
Abstract
2624 - Efficacy of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer patients with sensitive genes mutation
Presenter: Hui-Juan Cui
Session: Poster Display session 3
Resources:
Abstract
3494 - Neutrophil to Lymphocyte Ratio (NLR) kinetics as predictors of outcomes in metastatic renal cell carcinoma (mRCC) and non-small cell lung cancer (NSCLC) patients treated with nivolumab (N).
Presenter: Audrey Simonaggio
Session: Poster Display session 3
Resources:
Abstract
3041 - Blood-based TMB (bTMB) correlates with tissue-based TMB (tTMB) in a multi-cancer Phase I IO Cohort
Presenter: Daniel Araujo
Session: Poster Display session 3
Resources:
Abstract
3910 - Analysis of Molecular Profile Complexities for Immunotherapy Decision Support
Presenter: Robert Dóczi
Session: Poster Display session 3
Resources:
Abstract
4836 - The Role of Tumor Neoantigens in the Differential Response to Immunotherapy (IO) in EGFR and BRAF Mutated Lung Cancers - Quantity or Quality?
Presenter: Katrina Case
Session: Poster Display session 3
Resources:
Abstract
1929 - Impact of previous corticosteroid (CS) exposure on efficacy of Programmed Cell Death-(Ligand) 1 blockade in patients with advanced Non-Small-Cell Lung Cancer (NSCLC): a single Center retrospective analysis
Presenter: Fabrizio Nelli
Session: Poster Display session 3
Resources:
Abstract
2601 - Comparison 18F-FDG-PET/CT criteria for prediction of therapy response and clinical outcome in patients with metastatic melanoma treated with Ipilimumab and PD-1 inhibitors
Presenter: Sabrina Vari
Session: Poster Display session 3
Resources:
Abstract
3628 - Predictive model for survival in advanced non-small-cell lung cancer (NSCLC) treated with frontline pembrolizumab
Presenter: Xabier Mielgo Rubio
Session: Poster Display session 3
Resources:
Abstract