ASCO 2021: Medical Oncologist Perspective: The Promise and Limitations of Precision Health in Metastatic Disease
There are at least two ways to assay for tumor mutational changes, either by biopsy of a metastatic site or by the identification of circulating tumor DNA. Metastatic biopsy has a variable yield of adequate DNA for tissue sequencing, ranging from 30-75% based on the site. Multiple commercial platforms are available for doing such sequencing, and there is no standardized reporting format currently.
Dr. Huang then reviewed the two clinical trials of PARP inhibitors that led to FDA approval for olaparib (if alteration in one of fifteen homologous recombination genes is detected) and rucaparib (if an alteration in BRCA1 or BRCA2). These were the PROFOUND and TRITON2 studies, respectively. Importantly, not all alterations in homologous recombination genes confer equal sensitivity to PARP inhibitors, with BRCA2 showing the strongest evidence of response. Furthermore, the role of PARP inhibitors in tumors that do not have specific gene alterations within the homologous recombination repair pathway is also being investigated.
Microsatellite instability or mismatch repair deficiency is present in 2-3% of metastatic castration resistant prostate cancer. Testing for this alteration by either immunohistochemistry (mismatch repair deficiency) or tumor sequencing (microsatellite instability) is recommended given the FDA approval for pembrolizumab in these tumors agnostic of tumor type.
Finally, Dr. Huang reviewed current challenges to delivering precision medicine driven by genomic testing in prostate cancer. He identified the issues of delivering care equitably, the challenge of getting adequate tumor DNA from certain sites like bone, and confounding of tumor sequencing results by the presence of alterations due to clonal hematopoiesis. Future work must focus on equal outreach and education to patients regardless of socioeconomic status to facilitate the application of precision medicine when beneficial, gaining increased experience with metastatic biopsy, and tumor-normal paired sequencing to rule out germline variants unrelated to prostate cancer.
Presented by: Franklin W. Huang, MD, PhD, Assistant Professor in the Department of Medicine and Medical Oncologist at the University of California San Francisco, San Francisco, California
Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021