Priscilla K. Brastianos, MD, on CNS Metastases: Understanding Their Evolution and the Clinical Implications
AACR Annual Meeting 2022
Priscilla K. Brastianos, MD, of Harvard Medical School and Massachusetts General Hospital, talks about her efforts to better understand how brain metastases evolve genomically and to test such agents as abemaciclib, paxalisib, and entrectinib, which may stop their growth. Palbociclib, a CDK inhibitor, has already shown potential benefit. A national cooperative group trial is underway in multiple centers to identify novel treatments for patients with brain metastases, who typically have a poor prognosis (Abstract SY38).
The ASCO Post Staff
Timothy A. Yap, MBBS, PhD, of The University of Texas MD Anderson Cancer Center, discusses results from the PETRA study, a first-in-class, first-in-human trial of the next-generation PARP1-selective inhibitor AZD5305 in patients with BRCA1/2, PALB2, or RAD51C/D mutations in advanced or metastatic ovarian cancer, HER2-negative breast cancer, pancreatic, or prostate cancer. Target engagement was demonstrated across all dose levels, and antitumor activity was observed in selected tumor and molecular subtypes.
The ASCO Post Staff
Benoit You, MD, PhD, of the Lyon University Hospital (France), discusses phase I/II safety and efficacy results from the ENDOLA trial that combined olaparib with metronomic cyclophosphamide and metformin in patients with advanced pretreated endometrial cancer. At 10 weeks, the non–disease progression rate was 61.5%, reaching the primary endpoint of the study. Median progression-free survival was 5.1 months. Research on biomarkers of efficacy is ongoing (Abstract CT005).
The ASCO Post Staff
Alana L. Welm, PhD, of the University of Utah Huntsman Cancer Institute, discusses her findings of a new pathway that regulates the antitumor immune response during metastatic outgrowth. Interfering with a particular isoform of RON kinase may cause metastatic tumors to be swarmed by T cells and killed, suggesting that new approaches to targeting this kinase may be achievable in the near future (Abstract SY32).
The ASCO Post Staff
Timothy A. Yap, MBBS, PhD, of The University of Texas MD Anderson Cancer Center, discusses how research is building on the success of first-generation PARP inhibitors in the clinic and the potential of novel potent PARP1-selective inhibitors, which may lead to improved patient outcomes. Given recent advances in drug discovery, says Dr. Yap, we now can go beyond PARP by drugging other key DNA damage response targets in the clinic, including ATR, WEE1, DNA-PK, RAD51, POLQ, and USP1.
The ASCO Post Staff
David A. Barbie, MD, of Dana-Farber Cancer Institute, discusses his laboratory’s studies, showing that malignant pleural mesothelioma, an inflamed cancer type with marginal response to immune checkpoint blockade, demonstrated high tumor cell STING expression and response to STING agonists in combination with natural killer cell therapies ex vivo. STING is the tumor cell stimulator of interferon genes (Abstract 4168).
