Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago.

In this episode, OncLive On Air® partnered with Two Onc Docs to highlight chronic lymphocytic leukemia (CLL) updates from the 2025 ASH Annual Meeting. Drs Armstrong and Tawagi noted that CLL is typically diagnosed in asymptomatic, elderly individuals presenting with lymphocytosis. A definitive diagnosis is established by confirming the clonality of circulating B lymphocytes via immunoglobulin light chain restriction on flow cytometry, they explained. Treatment initiation is reserved for active disease, which is indicated by B symptoms, progressive cytopenias, threatened organ function, or bulky disease such as splenomegaly, they said.

They continued by reporting several prognostic features that denote poor outcomes. Current standard frontline regimens use covalent BTK inhibitors or time-limited targeted regimens that include venetoclax (Venclexta), often combined with an anti-CD20 monoclonal antibody, according to the experts. They added that TKI-based therapy is preferred for patients with high-risk features.

The phase 3 BRUIN CLL-313 trial (NCT05023980) investigated pirtobrutinib (Jaypirca), a highly selective noncovalent BTK inhibitor, compared with bendamustine and rituximab (BR) in patients with treatment-naive CLL. The trial showed a significant improvement in progression-free survival with pirtobrutinib vs BR. Pirtobrutinib was also associated with a favorable safety profile, with modest rates of class-associated toxicities, including all-grade bleeding, arthralgia, and atrial fibrillation.

Although pirtobrutinib showed superior efficacy in BRUIN CLL-313, the clinical interpretation of these data is complicated because BR is an outdated control arm compared with contemporary frontline standards, Armstrong and Tawagi emphasized. Furthermore, the requirement for indefinite therapy with BTK inhibitors is a sequencing challenge, particularly as pirtobrutinib is currently approved in the post-covalent BTK inhibitor setting, they continued. However, its favorable toxicity profile suggests potential utility in elderly patients with pre-existing cardiovascular comorbidities, they noted. Future studies are focused on comparing pirtobrutinib vs time-limited venetoclax and evaluating various triplet regimens, they concluded.

From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilcon Family Chair at the Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

In this episode, Dr Matulonis sat down with guest Panagiotis (Panos) A. Konstantinopoulos, MD, PhD, to discuss the different subtypes of endometrial cancer and treatment developments for this disease. Dr Konstantinopoulos is the director of Translational Research in the Division of Gynecologic Oncology, the director of the Mellen and Eisenson Family Center for BRCA and Related Genes, and the Velma Eisenson Chair for Clinical and Translational Research at Dana-Farber Cancer Institute; as well as a professor of medicine at Harvard Medical School.

Drs Matulonis and Konstantinopoulos explained that patients with mismatch repair–deficient (dMMR) tumors substantially benefit from a decreased risk of progression or death when immunotherapy is added to standard therapy. They noted that immunotherapy appears important for the management of dMMR tumors, even those in earlier stages or in patients who have no measurable disease remaining after surgery.

For MMR-proficient (pMMR) tumors, Drs Matulonis and Konstantinopoulos highlighted that PD-1 blockade combined with chemotherapy improves survival vs chemotherapy alone, but that this benefit is not as substantial as that seen in dMMR disease. Crucially, they reported that if a pMMR tumor has no measurable disease after surgery, adding immune checkpoint blockade does not appear beneficial. They stated that tailored treatment approaches are key for managing pMMR disease subtypes. They added that hormonal therapy may be used upfront for slow-growing, estrogen receptor–positive metastatic disease.

They continued by saying that DNA damage and replication stress are critical targets, particularly in p53-mutated tumors, like uterine serous cancers. Furthermore, they stressed that although the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (Enhertu) is highly effective in HER2-positive tumors, treatment with this agent requires monitoring for toxicities, including interstitial lung disease and decreased ejection fraction.

In this episode, Gregory J. Tiesi, MD, FACS, FSSO, hosted a discussion about the use of hepatic artery infusion (HAI) in colon cancer and liver cancer management. Dr Tiesi is the medical director of Hepatobiliary Surgery at the Hackensack Meridian Jersey Shore University Medical Center in Neptune, New Jersey. He was joined by:

Drs Tiesi, Scholer, Golas, and Pletcher explained that HAI is a longstanding regional therapy used for treating primary and metastatic tumors to the liver, notably unresectable colorectal liver metastases and intrahepatic cholangiocarcinoma. The physiologic mechanism of this treatment leverages the dual blood supply of the liver, capitalizing on the fact that these malignancies primarily derive their perfusion from the hepatic artery, the experts noted. They emphasized that by delivering chemotherapeutic agents, such as floxuridine, directly via the gastroduodenal artery, HAI concentrates drug exposure at the tumor site, maximizing antitumor effect and minimizing extrahepatic toxicity. 

They explained that patient selection requires fitness for surgery and good liver function, excluding those with cirrhosis or portal hypertension. They also noted that the procedure involves implanting a subcutaneous pump, followed by rigorous intraoperative and postoperative nuclear medicine studies to confirm the absence of extrahepatic perfusion. Evidence supports that HAI combined with systemic therapy achieves higher intrahepatic objective responses, improves local disease control, and enhances conversion to resectability, correlating with improved long-term survival, the experts reported. However, potential complications include pump pocket infections, biliary sclerosis, and gastric ulcers, they added. The experts concluded by highlighting that establishing an HAI program necessitates a robust, multidisciplinary approach involving surgical oncology, medical oncology, and interventional radiology.

In today’s episode, we had the pleasure of speaking with Catherine Shu, MD, about the use of tepotinib (Tepmetko) in patients with non–small cell lung cancer harboring MET exon 14 skipping mutations. Dr Shu is the Price Family Associate Professor of Medicine and the clinical director of the Thoracic Medical Oncology Service at the Columbia University Herbert Irving Comprehensive Cancer Center in New York, New York. 

In our exclusive interview, Dr Shu discussed updated data from the phase 2 VISION trial (NCT02864992) that investigated tepotinib in this population, the notable efficacy of this agent in treatment-naive patients, and considerations for managing and mitigating the adverse effects associated with this therapy. 

In this episode, Gregory J. Tiesi, MD, FACS, FSSO, hosted a discussion about innovations in regional cancer therapies. Dr Tiesi is the medical director of Hepatobiliary Surgery at the Hackensack Meridian Jersey Shore University Medical Center in Neptune, New Jersey. He was joined by:

Drs Tiesi, Scholer, Golas, and Pletcher chatted about the use of pressurized intraperitoneal aerosolized chemotherapy (PIPAC), a minimally invasive regional cancer therapy designed for patients with peritoneal metastases or primary peritoneal cancers. The experts explained that this laparoscopic approach overcomes several limitations of traditional systemic treatments by delivering aerosolized chemotherapy in fine droplets under high pressure into the peritoneal cavity. This process ensures uniform drug distribution and enhanced tissue penetration, allowing for efficacy with lower systemic drug concentrations, they noted. 

PIPAC candidates typically present with unresectable or recurrent disease, or symptomatic malignant ascites, and should have an ECOG performance status between 0 and 2, they elaborated. The procedure, which is repeatable every 4 to 6 weeks, includes diagnostic laparoscopy, quantification of the peritoneal carcinomatosis index, and serial biopsies to assess treatment response. They emphasized that PIPAC has a favorable safety profile, with low 30-day mortality rates and minimal grade 3/4 adverse effects reported in clinical trials. Additionally, they stated that clinical data indicate high pathologic response rates and the potential for disease downstaging, enabling some patients who were initially deemed unresectable to become eligible for subsequent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Of note, the experts reported that PIPAC is designed to be integrated seamlessly with concurrent systemic therapy.

In today’s episode, we had the pleasure of speaking with Sarah Rutherford, MD, about the evolving role of minimal residual disease (MRD) and circulating tumor DNA (ctDNA) testing for lymphoma treatment decision-making. Dr Rutherford is an associate professor of clinical medicine in the Division of Hematology/Oncology at Weill Cornell Medicine in New York, New York. 

In our exclusive interview, Dr Rutherford discussed the usefulness of ctDNA for guiding patient treatment, clinical trials that are ongoing to determine the best use of this type of assay, how personalized ctDNA testing offers the potential for disease surveillance and effective intervention, key hurdles in the way of widespread implementation of ctDNA testing in clinical practice, and how integration with next-generation sequencing is expected to further tailor treatment strategies.

In today’s episode, we had the pleasure of speaking with Shubham Pant, MD, MBBS, about the first-line treatment of patients with metastatic pancreatic cancer. Dr Pant is a professor in the Department of Gastrointestinal (GI) Medical Oncology of the Division of Cancer Medicine, director of Clinical Research, and a professor in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center in Houston.

In our exclusive interview, Dr Pant discussed factors that drive frontline chemotherapy selection for metastatic pancreatic cancer, the role of NALIRIFOX (irinotecan liposome [Onivyde], oxaliplatin, 5-fluorouracil, and leucovorin) in this treatment setting, and how the first-line treatment paradigm may evolve and expand going forward.

In today’s episode, we had the pleasure of speaking with Jacob Sands, MD, and Shailee Shah, MD, about considerations for diagnosing and managing Lambert-Eaton myasthenic syndrome (LEMS), particularly in the context of small cell lung cancer (SCLC). Dr Sands is associate chief of the Lowe Center for Thoracic Oncology and the Oncology Medical Director of the International Patient Center at Dana-Farber Cancer Institute, as well as an assistant professor at Harvard Medical School in Boston, Massachusetts. Dr Shah is a clinical assistant professor of neurology (MS/neuroimmunology) at the Northwestern University Feinberg School of Medicine in Chicago, Illinois. 

In our exclusive interview, Drs Sands and Shah discussed LEMS symptom identification, the importance of paraneoplastic panels for assessing neurologic dysfunction in patients with SCLC, the need for specific autoantibody testing, and what guidelines currently note as best practices for the diagnosis of this disease. 

Welcome to OncLive On Air®!

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, we had the pleasure of speaking with Joshua Richter, MD, about the rationale and implications for the phase 1 CAMMA 1 study (NCT04910568), which is investigating the bispecific antibody cevostamab (RG6160; BFCR4350A) in patients with relapsed/refractory multiple myeloma. Dr Richter is an associate professor of medicine at The Tisch Cancer Institute and director of Multiple Myeloma at the Blavatnik Family Chelsea Medical Center at Mount Sinai in New York, New York.

In our exclusive interview, Dr Richter discussed the rationale for targeting FcRH5 in the development of therapies for multiple myeloma, the evaluation of cevostamab-based combination strategies in patients with relapsed/refractory disease, and what the future may hold in this research arena. 

Welcome to OncLive On Air®!

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, we had the pleasure of speaking with Cassie Kline, MD, MAS, about updated efficacy data from the phase 2 FIREFLY-1 study (NCT04775485) of tovorafenib (Ojemda) in patients with relapsed/refractory pediatric low-grade glioma (pLGG) that were presented at the 2025 Society of Neuro-Oncology Annual Meeting. Dr Kline is an attending physician and director of Clinical Research in the Department of Neuro-Oncology at Children's Hospital of Philadelphia in Pennsylvania.

In our exclusive interview, Dr Kline discussed longer-term efficacy and safety data from the trial, noting the sustained response rates, continued tumor shrinkage, and rates of patients who remained treatment free after approximately 36 months of follow-up.

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