Manifestations include multi organ benign and malignant angiogenic tumors, necessitating repeat surgery quite often. There have been previous studies of VEGF inhibitors for VHL disease demonstrating some response. Dr. Jonasch presented a phase 2 study of 32 VHL patients with measurable lesions receiving Pazopanib 800 mg PO daily for up to 24 weeks with the primary endpoint being response. Results showed that Pazopanib stabilized or regressed most lesions but no complete response was noted. After 24 weeks only 8 patients continued with the drug, while 7 stopped due to toxicities and 11 stopped by choice.
Dr. Sonpavde then moved to the 2nd abstract by Dr. Sumanta: Comprehensive genomic profiling (CGP) of advanced papillary renal cell carcinoma (PRCC) to reveal distinctions from TCGA dataset. This study included 169 cases of PRCC with 60% being stage 4 disease. All formalin-fixed paraffin-embedded (FFPE) specimens underwent genomic profiling of up to 315 genes and hotspots of 31 selected genes. Results showed that TERT (promoter mutations) and MET H1094 are most frequently altered. Additionally, the MET, FH, NF2, SWI/SNF mutations were more frequent than TCGA. This is the largest study of genomic profiling of advanced PRCC, but it still requires external validation.
The third and last study summarized by Dr. Sonpavde was abstract 4518, presented by Dr. Rodney: Multi-region sequencing of penile cancer to reveal distinct patterns of heterogeneous actionable mutations. Penile carcinoma is a rare disease composed of squamous cell carcinoma in 90% of cases. There are approximately 1600 cases per year with 270 deaths in the USA. Its incidence is higher in parts of Africa, Asia and South America, with an estimated 26000 cases per year. The etiology and molecular biology of this disease is poorly understood. There is a known association to HPV, smoking and lack of neonatal circumcision. Median age of diagnosis is 58 with suboptimal overall survival (OS) under current systemic therapy. In the current study targeted next generation sequencing of 20-43 penile squamous cell carcinoma cases was done (PSCC). The most common alterations that were found included p53 (65%), CDKN2A (40%), NOTCH1 (25%) and PIK3CA (25%). Whole exome sequencing (WES) was also performed on 27 patients. Results showed that there is extensive intra- and inter-tumour heterogeneity within penile cancer. The main truncal drivers in penile cancer were shown to be cMET, FAT1 and p53. Samples infected with human papillomavirus appeared to have a distinct signature in terms of both copy number changes and clonal architecture. Actionable mutations PIK3CA and EGFR were found to be subclonal in origin. This may have profound effects on the clinical utility of targetable treatments such as tyrosine kinase inhibitors.
Dr. Sonpavde concluded his presentation by stating that 20% of cancer patients in the USA are diagnosed with a rare cancer. The rare cancer research foundation (RCRF) provides research infrastructure- patient registries, tissue samples, cell lines, animal models, and genome sequencing. Additionally, RCRF has already several clinical trials lined up.
Speaker: Guru Sonpavde, MD, Division of Hematology & Oncology, University of Alabama, Birmingham, Alabama
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre