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
5595 - Is there any prognostic significance in pleural involvement and/or effusion (Ple-I/E) in patients with ALK-positive NSCLC?
Presenter: Saadettin Kilickap
Session: Poster Display session 1
Resources:
Abstract
5840 - Crizotinib in patients with advanced or metastatic ROS1-rearranged lung cancer (EUCROSS): A European phase 2 clinical trial – Updated progression-free survival, overall survival and mechanisms of resistance
Presenter: Sebastian Michels
Session: Poster Display session 1
Resources:
Abstract
1905 - NTRK1-3 Genomic Fusions in Non-Small Cell Lung Cancer (NSCLC) Determined by Comprehensive Genomic Profiling
Presenter: Sai-Hong Ou
Session: Poster Display session 1
Resources:
Abstract
3016 - Preferential expression of the affected MET allele in lung carcinomas with heterozygous MET exon 14 skipping mutations: implications for clinical testing
Presenter: Evgeny Imyanitov
Session: Poster Display session 1
Resources:
Abstract
4120 - Brain metastases, treatment patterns and outcomes in ROS1-positive NSCLC patients from US oncology community centers
Presenter: Matthew G Krebs
Session: Poster Display session 1
Resources:
Abstract
3764 - Patients with metastatic non-small cell lung cancer and targetable molecular alterations in Germany. Treatment and first outcome data from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Frank Griesinger
Session: Poster Display session 1
Resources:
Abstract
4070 - Crizotinib vs Platinum-based Chemotherapy as First-line Treatment for Advanced Non-small Cell Lung Cancer with Different ROS1 Fusion Variants
Presenter: Haiyan Xu
Session: Poster Display session 1
Resources:
Abstract
5528 - Genomic and clinical characterization of Non-small cell lung cancer (NSCLC) patients harboring mutations in FGFR2 and FGFR3
Presenter: Matthias Scheffler
Session: Poster Display session 1
Resources:
Abstract
3779 - The expression of HER2-gene polymorphisms -1985G>T and P1170A C>G and their association with the risk of development of lung adenocarcinoma
Presenter: Ivan Aleric
Session: Poster Display session 1
Resources:
Abstract
3020 - Circulating tumor DNA (ctDNA) analysis depicts mechanisms of resistance and tumor response to BRAF inhibitors in BRAF-mutant non-small cell lung cancer (NSCLC)
Presenter: Sandra Ortiz - Cuaran
Session: Poster Display session 1
Resources:
Abstract