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
4634 - Comparative molecular analyses between microsatellite stable BRAFV600E mutant colorectal cancers and BRAFV600E mutant melanomas.
Presenter: Mohamed Salem
Session: Poster Display session 3
Resources:
Abstract
3264 - A novel preclinical model of RAF-independent MEK1 mutant tumors and its treatment with novel ATP competitive MEK inhibitor
Presenter: Luca Hegedus
Session: Poster Display session 3
Resources:
Abstract
4918 - HER2 inhibition in Aggressive Squamous Cell Carcinomas driven by a common MET Sema Domain Polymorphism
Presenter: Nur Afiqah Mohamed Salleh
Session: Poster Display session 3
Resources:
Abstract
2426 - ADAM9 as a target for lung cancer treatment
Presenter: Yuh-pyng Sher
Session: Poster Display session 3
Resources:
Abstract
5537 - Novel polyurea/polyurethane nanocapsules loaded with a tambjamine analog to improve cancer chemotherapy delivery and safety in lung cancer
Presenter: Marta Perez Hernandez
Session: Poster Display session 3
Resources:
Abstract
1597 - Discovery of Clinical Candidate DBPR112, a Furanopyrimidine-based Epidermal Growth Factor Receptor Inhibitor for the Treatment of Non-Small Cell Lung Cancer
Presenter: Hsing-pang Hsieh
Session: Poster Display session 3
Resources:
Abstract
3543 - Molecular characteristics in lung squamous cell carcinomas dependent on TP53 status – putative targets
Presenter: Vilde Haakensen
Session: Poster Display session 3
Resources:
Abstract
4111 - Comparison of molecular profiles between primary tumour and matched metastasis in non-small cell lung cancer
Presenter: Asuka Kawachi
Session: Poster Display session 3
Resources:
Abstract
4559 - Treatment with BLU-667, a potent and selective RET inhibitor, provides rapid clearance of ctDNA in Patients with RET-altered Non-Small Cell Lung Cancer (NSCLC) and Thyroid Cancer
Presenter: Giuseppe Curigliano
Session: Poster Display session 3
Resources:
Abstract
2501 - Triple MET/SRC/PIM inhibition in MET addicted tumors
Presenter: Ilaria Attili
Session: Poster Display session 3
Resources:
Abstract