Lillian L. Siu, MD, of Canada’s Princess Margaret Cancer Centre, discusses biomarker-driven precision cancer medicine, the optimal sequencing of immunotherapy (IO) with standard treatments in curative settings, IO targets beyond PD-1/PD-L1 and combinatorial strategies, and next-generation adoptive cell therapies (Abstract PL06).
Tina Cascone, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses the findings of the phase II NeoCOAST study, which showed that combination immunotherapy with the anti–PD-L1 monoclonal antibody durvalumab and other novel agents resulted in numerically higher major pathologic response rates than durvalumab alone in the neoadjuvant setting for patients with early-stage resectable non–small cell lung cancer. Translational results also supported combination therapies over single-agent therapy (Abstract CT011).
Charles L. Sawyers, MD, of Memorial Sloan Kettering Cancer Center, discusses the battle against treatment resistance and how to overcome it, as well as the power of observational clinical data in precision oncology, derived largely from his experience with Project GENIE, and the role of genetic ancestry (Abstract PL02).
Jia Luo, MD, of Dana-Farber Cancer Institute, discusses the emerging class of cancer therapies for allele-specific KRAS inhibitors and the importance of their distinct clinical, genomic, and immunologic features. Because KRAS G12D–mutated non–small cell lung cancer is associated with worse responses to immunotherapy, Dr. Luo believes drug development will need to take these differences into account (Abstract 4117).
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).
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.
