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
5705 - External validation and longitudinal extension of the LIPI (Lung Immune Prognostic Index) for immunotherapy outcomes in advanced non-small cell lung cancer.
Presenter: Jakob Riedl
Session: Poster Display session 3
Resources:
Abstract
5758 - Changes of TCR Repertoire in Metastatic Renal Cell Carcinoma and Metastatic Melanoma Patients Treated with Nivolumab
Presenter: Martin Klabusay
Session: Poster Display session 3
Resources:
Abstract
1743 - Expression of MHC class I, HLA-A and HLA-B identifies immune activated breast tumors with favorable outcome
Presenter: María Del Mar Noblejas López
Session: Poster Display session 3
Resources:
Abstract
2219 - Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression and Predictive Value of Circulating Tumor Cell Count Monitoring in Patients Receiving Racotumomab Immunotherapy
Presenter: Necdet Üskent
Session: Poster Display session 3
Resources:
Abstract
2996 - Evolution of Myeloid-Derived Suppressor Cells and Objective Response Rate in Relapsed/Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) patients after receiving immunotherapy
Presenter: Carlos Jiménez Cortegana
Session: Poster Display session 3
Resources:
Abstract
2110 - A Phase Ia/Ib trial of the anti-programmed death-ligand 1 (PD-L1) human monoclonal antibody (mAb), CS1001, in patients (pts) with advanced solid tumors or lymphomas
Presenter: Lin Shen
Session: Poster Display session 3
Resources:
Abstract
3515 - Results from a randomised Phase 1/2 trial evaluating the safety and antitumour activity of anti-PD-1 (MEDI0680)/anti-PD-L1 (durvalumab) vs anti-PD-1 (nivolumab) alone in metastatic clear cell renal cell carcinoma (ccRCC)
Presenter: Martin Voss
Session: Poster Display session 3
Resources:
Abstract
3566 - Pembrolizumab in Advanced Rare Cancers
Presenter: Aung Naing
Session: Poster Display session 3
Resources:
Abstract
3567 - High clinical benefit rates of pembrolizumab in very rare sarcoma histotypes: first results of the AcSé Pembrolizumab study
Presenter: Jean-Yves Blay
Session: Poster Display session 3
Resources:
Abstract
2421 - Lenvatinib plus PD-1 blockade in advanced bile tract carcinoma.
Presenter: Jianzhen Lin
Session: Poster Display session 3
Resources:
Abstract