Abstract
Analysis of the IMvigor 210 trials involving patients with platinum-refractory or cisplatin-ineligible urothelial carcinoma who were treated with the PD-L1 inhibitor atezolizumab identified a resistance signature as an immune biomarker. Transcriptome profiling of 368 tumor samples from this trial revealed that the “genomically unstable” Lund subtype classification was associated with the best response. We developed and applied a novel single-patient subtype classifier based on The Cancer Genome Atlas 2017 expression-based molecular subtypes. We identified 11 patients with a neuronal subtype, with a 100% response rate in eight confirmed cases (2 complete response, 6 partial response), and 72% overall, including 3/11 patients with an unconfirmed response. The survival probability was extraordinarily high for the neuronal subtype, which represents a high-risk cohort with advanced disease, and may be secondary to low levels of TGFβ expression and high mutation/neoantigen burden. Patient summary: We describe a methodology for genomic classification of an individual patient's bladder cancer tumor and have identified a subtype that is associated with a high response rate to immunotherapy. This is an important step forward in identifying the right treatment for the right patient, which is the goal of personalized precision medicine. We describe a novel single-patient classifier based on The Cancer Genome Atlas 2017 scheme that identified the neuronal subtype of urothelial carcinoma as an extreme responder to anti-PD-L1 therapy. In the future, trials targeting subtype-based therapy may improve precision delivery of care for urothelial carcinoma.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 961-964 |
| Number of pages | 4 |
| Journal | European urology |
| Volume | 75 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2019 |
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Keywords
- Anti-PD-L1 antibody
- Bladder cancer
- Immunotherapy
- Neuronal
- RB1
- Subtypes
- TP53
- The Cancer Genome Atlas
- Urothelial cancer
ASJC Scopus subject areas
- Urology
Cite this
}
The Cancer Genome Atlas Expression Subtypes Stratify Response to Checkpoint Inhibition in Advanced Urothelial Cancer and Identify a Subset of Patients with High Survival Probability. / Kim, Jaegil; Kwiatkowski, David; McConkey, David J.; Meeks, Joshua J.; Freeman, Samuel S.; Bellmunt, Joaquim; Getz, Gad; Lerner, Seth P.
In: European urology, Vol. 75, No. 6, 06.2019, p. 961-964.Research output: Contribution to journal › Article
TY - JOUR
T1 - The Cancer Genome Atlas Expression Subtypes Stratify Response to Checkpoint Inhibition in Advanced Urothelial Cancer and Identify a Subset of Patients with High Survival Probability
AU - Kim, Jaegil
AU - Kwiatkowski, David
AU - McConkey, David J.
AU - Meeks, Joshua J.
AU - Freeman, Samuel S.
AU - Bellmunt, Joaquim
AU - Getz, Gad
AU - Lerner, Seth P.
PY - 2019/6
Y1 - 2019/6
N2 - Analysis of the IMvigor 210 trials involving patients with platinum-refractory or cisplatin-ineligible urothelial carcinoma who were treated with the PD-L1 inhibitor atezolizumab identified a resistance signature as an immune biomarker. Transcriptome profiling of 368 tumor samples from this trial revealed that the “genomically unstable” Lund subtype classification was associated with the best response. We developed and applied a novel single-patient subtype classifier based on The Cancer Genome Atlas 2017 expression-based molecular subtypes. We identified 11 patients with a neuronal subtype, with a 100% response rate in eight confirmed cases (2 complete response, 6 partial response), and 72% overall, including 3/11 patients with an unconfirmed response. The survival probability was extraordinarily high for the neuronal subtype, which represents a high-risk cohort with advanced disease, and may be secondary to low levels of TGFβ expression and high mutation/neoantigen burden. Patient summary: We describe a methodology for genomic classification of an individual patient's bladder cancer tumor and have identified a subtype that is associated with a high response rate to immunotherapy. This is an important step forward in identifying the right treatment for the right patient, which is the goal of personalized precision medicine. We describe a novel single-patient classifier based on The Cancer Genome Atlas 2017 scheme that identified the neuronal subtype of urothelial carcinoma as an extreme responder to anti-PD-L1 therapy. In the future, trials targeting subtype-based therapy may improve precision delivery of care for urothelial carcinoma.
AB - Analysis of the IMvigor 210 trials involving patients with platinum-refractory or cisplatin-ineligible urothelial carcinoma who were treated with the PD-L1 inhibitor atezolizumab identified a resistance signature as an immune biomarker. Transcriptome profiling of 368 tumor samples from this trial revealed that the “genomically unstable” Lund subtype classification was associated with the best response. We developed and applied a novel single-patient subtype classifier based on The Cancer Genome Atlas 2017 expression-based molecular subtypes. We identified 11 patients with a neuronal subtype, with a 100% response rate in eight confirmed cases (2 complete response, 6 partial response), and 72% overall, including 3/11 patients with an unconfirmed response. The survival probability was extraordinarily high for the neuronal subtype, which represents a high-risk cohort with advanced disease, and may be secondary to low levels of TGFβ expression and high mutation/neoantigen burden. Patient summary: We describe a methodology for genomic classification of an individual patient's bladder cancer tumor and have identified a subtype that is associated with a high response rate to immunotherapy. This is an important step forward in identifying the right treatment for the right patient, which is the goal of personalized precision medicine. We describe a novel single-patient classifier based on The Cancer Genome Atlas 2017 scheme that identified the neuronal subtype of urothelial carcinoma as an extreme responder to anti-PD-L1 therapy. In the future, trials targeting subtype-based therapy may improve precision delivery of care for urothelial carcinoma.
KW - Anti-PD-L1 antibody
KW - Bladder cancer
KW - Immunotherapy
KW - Neuronal
KW - RB1
KW - Subtypes
KW - TP53
KW - The Cancer Genome Atlas
KW - Urothelial cancer
UR - http://www.scopus.com/inward/record.url?scp=85062371445&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062371445&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2019.02.017
DO - 10.1016/j.eururo.2019.02.017
M3 - Article
C2 - 30851984
AN - SCOPUS:85062371445
VL - 75
SP - 961
EP - 964
JO - European Urology
JF - European Urology
SN - 0302-2838
IS - 6
ER -