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• S14 Ep64: Optimized Immunotherapy Use and Novel Therapeutic Targets Move the Needle for Endometrial Cancer Management: With Ursula A. Matulonis, MD; and Panagiotis (Panos) A. Konstantinopoulos, MD, PhD

  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.

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• S14 Ep63: Hepatic Artery Infusion Refines Liver-Directed Care for GI Cancers: With Gregory J. Tiesi, MD, FACS, FSSO; Anthony Scholer, MD, FACS, FSSO; Benjamin Jon Golas, MD, FACS; and Eric Pletcher, MD

  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 Toms River and Brick, New Jersey. He was joined by: Anthony Scholer, MD, FACS, FSSO, a surgical oncologist specializing in hepatobiliary surgery, at Hackensack Meridian Medical Group and Jersey Shore University Medical Center in Neptune, New Jersey Benjamin Jon Golas, MD, FACS, regional chief of Surgical Oncology for Hackensack Meridian Health’s Central Region, surgical director of Oncology Services at Jersey Shore University Medical Center, vice chair of Surgery at Jersey Shore University Medical Center Cancer Surgery, and an associate professor of surgery at the Hackensack Meridian School of Medicine in Neptune and Edison, New Jersey Eric Pletcher, MD, a surgeon specializing in Complex General Surgical Oncology at Hackensack Meridian JFK University Medical Center in Edison 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.

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• S14 Ep62: VISION Data Show Promise of Tepotinib in Treatment-Naive NSCLC Harboring MET Exon 14 Skipping Mutations: With Catherine Shu, MD

  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. 

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• S14 Ep61: PIPAC Reshapes Peritoneal Cancer Surgery Workflows and Outcomes: With Gregory J. Tiesi, MD, FACS, FSSO; Anthony Scholer, MD, FACS, FSSO; Benjamin Jon Golas, MD, FACS; and Eric Pletcher, MD

  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 Toms River and Brick, New Jersey. He was joined by: Anthony Scholer, MD, FACS, FSSO, a surgical oncologist specializing in hepatobiliary surgery, at Hackensack Meridian Medical Group and Jersey Shore University Medical Center in Neptune, New Jersey Benjamin Jon Golas, MD, FACS, regional chief of Surgical Oncology for Hackensack Meridian Health’s Central Region, surgical director of Oncology Services at Jersey Shore University Medical Center, vice chair of Surgery at Jersey Shore University Medical Center Cancer Surgery, and an associate professor of surgery at the Hackensack Meridian School of Medicine in Neptune and Edison, New Jersey Eric Pletcher, MD, a surgeon specializing in Complex General Surgical Oncology at Hackensack Meridian JFK University Medical Center in Edison 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.

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• S14 Ep60: ctDNA Assays Are Poised to Reshape Lymphoma Treatment Strategies: With Sarah Rutherford, MD

  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.

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