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
3620 - Safety, efficacy, PK and PD biomarker results of the first-in-human study of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor BAY 1436032 in patients (pts) with mIDH1 advanced solid tumours
Presenter: Wolfgang Wick
Session: Poster Display session 1
Resources:
Abstract
5465 - Proof of concept clinical study by US-guided intratumor injection of VCN-01, an oncolytic adenovirus expressing hyaluronidase in patients with pancreatic cancer
Presenter: Manuel Hidalgo
Session: Poster Display session 1
Resources:
Abstract
2555 - A Phase 1a/b first-in-human, open-label, dose-escalation, safety, PK and PD study of TP-0903 in solid tumors
Presenter: John Sarantopoulos
Session: Poster Display session 1
Resources:
Abstract
3533 - First in human phase 1/2a study of PEN-866, a Heat Shock Protein 90 (HSP90) ligand – SN38 conjugate for patients with advanced solid tumors: Phase 1 results
Presenter: Johanna Bendell
Session: Poster Display session 1
Resources:
Abstract
4114 - A Phase I Open-Label, Non-Randomized Study of Recombinant Super-Compound Interferon (rSIFN-co) In Patients with Advanced Solid Tumors
Presenter: Amanda Seet
Session: Poster Display session 1
Resources:
Abstract
2537 - Evaluation of Pharmacodynamic (PD) Biomarkers in Advanced Cancer Patients Treated with Oxidative Phosphorylation (OXPHOS) Inhibitor, OPC-317 (OPC)
Presenter: Jie Qing Eu
Session: Poster Display session 1
Resources:
Abstract
5764 - Pharmacokinetic (PK) assessment of BT1718: A phase 1/2a study of BT1718, a first in class Bicycle Toxin Conjugate (BTC), in patients (pts) with advanced solid tumours
Presenter: Natalie Cook
Session: Poster Display session 1
Resources:
Abstract
2683 - A phase I open label dose escalation trial evaluating VT1021 in patients with advanced solid tumors.
Presenter: Wael Harb
Session: Poster Display session 1
Resources:
Abstract
3609 - Interim Results from Trial of SL-801, a Novel XPO-1 Inhibitor, in Patients with Advanced Solid Tumors
Presenter: Judy Wang
Session: Poster Display session 1
Resources:
Abstract
3485 - Phase 1 Trial of Fruquintinib in Patients with Advanced Solid Tumors: Results of the Dose Escalation Phase
Presenter: Andrea Wang-Gillam
Session: Poster Display session 1
Resources:
Abstract