AUA 2017: Creating an Institution-Wide Systems Biology Initiative
Dr. Solit started by defining his goals for cancer care at Memorial Sloan Kettering: 1) To define molecular drivers in EVERY patient. 2) To facilitate enrollment onto rational clinical trials. 3) To identify germline variants that predispose to cancer.
To do this, they have instituted a "front door" patient consent for exhaustive genetic and genomic testing of tumor tissue (formalin fixed paraffin embedded), and germline alterations (from peripheral blood). They are currently utilizing the MSK-IMPACT assay which is a home-grown next generation DNA sequencing assay focusing on 468 genes currently known to be important in cancer. The number of genes in this assay has increased over time, and is limited only by cost (with Dr. Solit's target of $1000 per patient/tumor). Interestingly, the percentage of cancer types for which this cost can be billed to insurance is currently around 50% and expected to rise as more outcomes data are generated.
The high throughput and transparency of the platform is impressive. All data is shared institution-wide in realtime using cloud-based software called CBioPortal. So far 17,000 tumors in 16,000 patients have been sequenced including 1100 prostate cancers and 500 bladder cancers. Importantly, this information is released to patients and may also be publicly available.
The main goal is to recruit patients to basket studies (studies in multiple tumor types with common mutations) with rational therapeutics to see if the mutation predicts for clinical activity. At the same time, identification of novel mutations is possible, and a case was described for a HER2 V777L activating mutation that was missed by prior analyses, and predicted response to the novel HER2 TKI neratinib.
Dr. Solit described a few patients with gastric and prostate cancer whose sequencing results uncovered microsatellite instability (both germline and somatic). The increased neoantigen burden in these MSI patients is thought to correlate with response to immunotherapies and these patients showed excellent responses. The penetrance of MSI in prostate cancer is ~2%, but Dr. Solit described a patient with multi-drug resistant mCRPC who had a remarkable response to immunotherapy and is now currently off ADT completely. Dr. Solit suspects this patient may be the first mCRPC he has ever cured as a medical oncologist.
Presented by: David Solit, MD MSKCC
Contributed by: Jed Ferguson, MD/PhD and Ashish Kamat, MD. MD Anderson Cancer Center, Department of Urology.
at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA