Abstract 5933
Background
Sequencing studies have demonstrated extensive genetic heterogeneity between and within tumor lesions in treated metastatic solid tumor patients. The response of individual tumor lesions to therapy is a reflection of subclonal inhibition and growth in the face of selective pressure. Are there lesion-level progression patterns that would provide insights into the biological heterogeneity that underpins response and resistance?.
Methods
Retrospective review of patients with histologically confirmed metastatic solid tumors who were treated at Massachusetts General Hospital Cancer Center’s phase 1 center from October 1, 2010 to September 30, 2015 and had at least two radiographic assessments, 30 days apart. 769 study participants were enrolled in a phase 1 trial during the study period, of which 575 had at least two radiographic evaluations. 427 participants had more than one lesion at baseline and displayed progression of at least one lesion (growth of at least 20% or a new lesion). We categorized the lesion-level progression patterns of these 427 patients.
Results
Study participants had a mean of 2.6 prior lines of therapy in the metastatic setting with an average of 6.3 tumor lesions on their baseline scan involving an average of 3 organs. Of the 427 study patients with progressive lesions, 24% of patients had progression at a single lesion and 49% of patients had progression in a single organ when they were taken off-study or at data cut-off. 10% of patients exhibited simultaneous response (shrinkage of at least 30%) and progression in different lesions. Across our entire 575 patient cohort, liver lesions were 2.9 times as likely to progress than other lesions regardless of cancer types.
Conclusions
The significant proportion of patients with progression at a single lesion or organ demonstrates that clonal heterogeneity has important clinical implications. Liver lesions may have microenvironment-specific factors that increase the likelihood of progression relative to other organ sites.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Chen: Advisory / Consultancy: Blackstone Life Sciences; Advisory / Consultancy: HotSpot Therapeutics; Advisory / Consultancy: Foundation Medicine. D. Juric: Advisory / Consultancy: Novartis; Advisory / Consultancy: Genentech; Advisory / Consultancy: Eisai; Advisory / Consultancy: Syros; Advisory / Consultancy: Ipsen; Research grant / Funding (self): Eisai; Research grant / Funding (self): Genentech; Research grant / Funding (self): Celgene; Research grant / Funding (self): Takeda; Research grant / Funding (self): javascript:%20create_table_line(’1’,%20new%20Array(’ent’,%20’des’,%20’tor’));Celgene; Research grant / Funding (self): Placon Therapeutics; Research grant / Funding (self): Syros; Research grant / Funding (self): EMD Serono; Research grant / Funding (institution): Novartis. All other authors have declared no conflicts of interest.
Resources from the same session
592 - Effects of novel targeted anticancer drugs on cytotoxicity, apoptosis, angiogenesis, EMT, drug resistance and autophagic mechanism
Presenter: Seyma Aydinlik
Session: Poster Display session 1
Resources:
Abstract
3235 - Delineating the mechanisms of alpha 1-3 fucosyltransferase FUT11 in ovarian cancer
Presenter: Qi Chen
Session: Poster Display session 1
Resources:
Abstract
3577 - The tyrosine kinase inhibitor Dasatinib blocks tumor growth, invasion and recurrence potential by interrupting the communication between cancer cells and their surrounding microenvironment in triple negative breast cancer
Presenter: Miriam Nuncia-Cantarero
Session: Poster Display session 1
Resources:
Abstract
4808 - NORE1A induces a feedback termination of TNF signaling by antagonizing TNFR1 through ITCH-mediated destruction complex
Presenter: Jieun Ahn
Session: Poster Display session 1
Resources:
Abstract
1294 - Hsp90 inhibitors enhance the antitumoral effect of osimertinib and overcome osimertinib resistance in non-small-cell cell lung cancer cell models
Presenter: Jordi Codony-Servat
Session: Poster Display session 1
Resources:
Abstract
1559 - Expression of IL-17RA promotes cancer stem-like properties of colorectal cancer cells by Stat3 activation
Presenter: Chih-Yung Yang
Session: Poster Display session 1
Resources:
Abstract
1615 - Adaption of Pancreatic Cancer Cells to AKT1 Inhibition Induces the Acquisition of Cancer Stem-Cell Like Phenotype Through Upregulation of Mitochondrial Functions
Presenter: Hugo Arasanz
Session: Poster Display session 1
Resources:
Abstract
4793 - Bub3 is phosphorylated by the Ataxia-Telangiectasia Mutated Kinase in mitosis and required for activation of the mitotic spindle checkpoint in Breast Cancer
Presenter: Mingming Xiao
Session: Poster Display session 1
Resources:
Abstract
1448 - The regulation of INK4 locus by long non-coding RNAs
Presenter: Yojiro Kotake
Session: Poster Display session 1
Resources:
Abstract
1858 - Vascular Endothelial Growth Factor in Colorectal Cancer Pathology, Survival and Treatment
Presenter: Liz Baker
Session: Poster Display session 1
Resources:
Abstract