Meenakshi Anurag, PhD, of Baylor College of Medicine, discusses results from the ALTERNATE trial, which showed the combination of anastrozole plus fulvestrant was superior to either drug alone in inhibiting tumor proliferation in postmenopausal women with early-stage luminal B breast cancer (Abstract CT026).
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).
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.
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).
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).
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).
