OncLive® On Air

In this podcast, experts Narjust Florez, MD, FASCO; David Carbone, MD, PhD; and Edward Garon, MD, MS; discuss the use of KRAS-, NRG1-, MET-, and ROS1-targeting agents to transform patient care in advanced non–small cell lung cancer (NSCLC).

In today’s episode, we sat down with John Marshall, MD, and Christopher Lieu, MD, to discuss the clinical relevance of KRAS G12C and pan-RAS inhibitors in the management of pancreatic and colorectal cancers. Dr Marshall is chief of Hematology and Oncology, a professor of medicine and oncology, and director of the Otto J Ruesch Center for the Cure of Gastrointestinal Cancers at the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC. Dr Lieu is a professor of medicine, associate director for Clinical Research, and co-director of Gastrointestinal Medical Oncology at the University of Colorado Anschutz and the University of Colorado Cancer Center in Aurora. 
In our exclusive interview, the experts highlighted historical challenges in targeting RAS mutations, as well as recent breakthroughs. They also emphasized the importance of testing early for biomarkers like Claudin 18.2, PD-L1, HER2, and microsatellite instability in patients with gastroesophageal cancers. Furthermore, the experts discussed the need to use targeted therapies early in treatment to avoid treatment resistance, and noted the potential of novel RAS inhibitors and immunotherapies. Their conversation also touched on the importance of rebiopsy and the challenges of obtaining sufficient tissue for biomarker analysis.

Breast Cancer Briefing, hosted by Sara Nunnery, MD, MSCI, a breast medical oncologist and the director of Breast Cancer Research at Tennessee Oncology in Nashville, is a podcast series that breaks down the latest news in breast cancer research, one conversation at a time.
In today's episode, filmed live onsite at the 43rd Annual Miami Breast Cancer Conference, Dr Nunnery sat down with Kelly E. McCann, MD, PhD, a breast medical oncologist in the University of California system.
Their conversation centered around the evolving HER2-positive breast cancer treatment paradigm. The experts highlighted that although this disease was once associated with a poor prognosis, targeted therapies like trastuzumab (Herceptin) have revolutionized management, making these cancers highly curable.
They noted the role of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), an antibody-drug conjugate (ADC) that delivers chemotherapy directly to cancer cells and uses a bystander effect to kill neighboring malignant cells. The phase 3 DESTINY-Breast11 trial (NCT05113251) evaluated T-DXd in the neoadjuvant setting for patients with high-risk, HER2-positive early breast cancer. Results showed significantly higher pathological complete response rates with T-DXd followed by docetaxel, trastuzumab, and pertuzumab (Perjeta) compared with standard chemotherapy. Responses were even more pronounced in patients with hormone receptor–negative disease.
Furthermore, they spotlighted the phase 3 DESTINY-Breast05 trial (NCT04622319), which examined T-DXd as adjuvant therapy for high-risk patients with residual HER2-positive disease. In this study, T-DXd generated an improvement in invasive disease–free survival compared with standard ado-trastuzumab emtansine (Kadcyla). They noted that a significant benefit of T-DXd is its ability to cross the blood-brain barrier, offering the potential for preventing brain metastases. However, the experts expressed caution regarding interstitial lung disease, a potentially fatal adverse effect associated with T-DXd. Because of this risk, patients who receive T-DXd require frequent, expensive CT monitoring, which Nunnery and McCann explained can pose logistical and insurance challenges in standard practice.
Although adjuvant T-DXd has been added to the National Comprehensive Cancer Network Clinical Practice Guidelines for HER2-positive breast cancer, the neoadjuvant regimen has not yet been included, likely awaiting more mature survival data. Both oncologists conclude that although ADC-associated toxicities require vigilant management, these treatment advancements provide powerful new tools for potentially curing high-risk patients with HER2-positive breast cancer.

In today’s episode, Jae Park, MD, discussed all things CAR T-cell therapy in acute lymphoblastic leukemia (ALL), touching on topics like where this treatment modality fits into the ALL paradigm, how it affects clinical practice, and how to go about selecting between the multiple FDA-approved options. Dr Park is the chief of the Cellular Therapy Service at Memorial Sloan Kettering Cancer Center in New York, New York. 
In our exclusive interview, Dr Park began with a conversation about the November 2024 FDA approval of obecabtagene autoleucel (obe-cel; Aucatzyl) and the October 2021 FDA approval of brexucabtagene autoleucel (brexu-cel; Tecartus) for patients with ALL. He explained how these CAR T-cell therapies fit into the ALL treatment paradigm for patients who have relapsed disease. After weighing how the safety and efficacy of each therapy stack up against others, Dr Park then discussed analyses that have come out after the obe-cel approval and their effect on obe-cel usage. Dr Park pointed out real-world studies presented at the 2025 ASH Annual Meeting, as well as analyses of the phase 1/2 FELIX trial (NCT04404660), which supported the approval of obe-cel. 
Finally, Dr Park looked ahead to the future of CAR T-cell therapies for ALL, noted in which settings he believes this class of agents will see the most use, and explained how to make treatment selections between therapies like brexu-cel and obe-cel.

Welcome to OncLive On Air®! I’m your host today, Ashling Wahner.
OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.
In today’s episode, Marina Baretti, MD, discussed the real-world utilization of tissue-free circulating tumor DNA (ctDNA) monitoring in cholangiocarcinoma (CCA). Baretti is an assistant professor and the Jiasheng Chair in Hepato-Biliary Cancer Research at Johns Hopkins University School of Medicine, as well as co-director of the Liver and Biliary Cancer Multidisciplinary Clinic at the Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland. 
In the exclusive interview, Dr Baretti discussed multiple potential roles for ctDNA testing in CCA management, including the detection of minimal residual disease following curative-intent surgery, longitudinal monitoring of treatment response in advanced disease, and identification of emergent resistance mechanisms with targeted therapy.
Baretti also reviewed findings from a small real-world observational analysis of 44 patients, in which a tissue-free ctDNA assay demonstrated high sensitivity, detecting variant allele frequencies as low as 0.2% and identifying actionable alterations in most patients; ctDNA dynamics also correlated with response and enabled early detection of resistance alterations, including secondary FGFR2 mutations, prior to radiographic progression in select cases.
Lastly, Baretti contextualized these findings within the broader treatment landscape by reviewing data from the phase 2 FIGHT-202 trial (NCT02924376), which supported the FDA approval of pemigatinib (Pemazyre) in patients with previously treated CCA harboring FGFR2 fusions or rearrangements. Real-world data have confirmed the efficacy and safety of this agent observed in clinical trials, reinforcing the importance of comprehensive molecular profiling.
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