Oncology On The Go

• S1 Ep148: Navigating Management and Dosing Considerations for Amivantamab in NSCLC

  In the first edition of a special 3-part podcast series, CancerNetwork® spoke with Daniel Morgensztern, MD; Mary Ellen Flanagan, NP; and Janelle Mann, PharmD, BCOP, about best practices for implementing recently approved bispecific antibodies into cancer care. Their initial discussion focused on the clinical trial results, administration protocols, and toxicity management strategies related to the use of amivantamab-vmjw (Rybrevant) for patients with EGFR-mutated non–small cell lung cancer (NSCLC). Morgensztern is a professor of Medicine and clinical director of Thoracic Oncology in the Division of Oncology at Washington University School of Medicine in St. Louis. Flanagan is a nurse practitioner in the Division of Thoracic Oncology at Washington University in St. Louis. Mann is a clinical oncology pharmacist at Siteman Cancer Center of Washington University School of Medicine in St. Louis and manager of Clinical Pharmacy Services at Barnes-Jewish Hospital. Morgensztern began by giving an overview of amivantamab’s mechanism of action and highlighting supporting data for the agent when administered alone or in combination with other agents.  The FDA initially approved amivantamab monotherapy for patients with EGFR exon 20 insertion–mutant NSCLC in May 2021 based on data from the phase 1 CHRYSALIS trial (NCT02609776). Furthermore, the agency approved amivantamab/chemotherapy as frontline treatment for patients with NSCLC harboring EGFR exon 20 insertion mutations in March 2024 based on data from the phase 3 PAPILLON trial (NCT04538664). Findings from the phase 3 MARIPOSA trial (NCT04487080) also supported the FDA approval of amivantamab plus lazertinib (Lazcluze) for those with EGFR-mutant NSCLC in August 2024. Additionally, Mann reviewed key dosing considerations as patients receive amivantamab via intravenous infusion. She detailed the use of premedication such as diphenhydramine (Benadryl) to supplement amivantamab while monitoring for toxicities during the initial infusion period, which may necessitate additional dosing adjustments. Flanagan added to the conversation surrounding infusion-related reactions by describing strategies for mitigating the risk of venous thromboembolism, cutaneous toxicities, and other adverse effects. References 1. RYBREVANTTM (amivantamab-vmjw) receives FDA approval as the first targeted treatment for patients with non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. May 21, 2021. Accessed January 29, 2025. https://tinyurl.com/3d8wtu4m 2. FDA approves amivantamab-vmjw for EGFR exon 20 insertion-mutated non-small cell lung cancer indications. News release. FDA. March 1, 2024. Accessed January 29, 2025. https://tinyurl.com/msw4u5yk 3. RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) approved in the U.S. as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. News release. Johnson & Johnson. August 20, 2024. Accessed January 29, 2025. https://tinyurl.com/yxc8u8t4

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• S1 Ep147: Expanding and Advancing the Future of Renal Cell Carcinoma Treatment

  In collaboration with KidneyCAN, CancerNetwork® spoke with Eric Jonasch, MD, a professor in the Department of Genitourinary Medical Oncology of the Division of Cancer Medicine, and the director of the von Hippel Lindau Center at the University of Texas MD Anderson Cancer Center in Houston, Texas, about the missions and goals of the Kidney Cancer Research Consortium. Jonasch is the principal investigator of an effort, supported by a Department of Defense (DoD)–funded grant, that aims to improve the treatment of patients with renal cell carcinoma (RCC) by developing a network of clinical trial centers that have expertise in both developing and executing new research efforts.  “We want to do the clinical trials that the industry wouldn’t do otherwise and do the trials that are going to allow us to gain knowledge faster,” Jonasch said. “We do this by, number one, using novel agents; number 2, using more efficient and innovative clinical trial designs; and, number 3, incorporating correlative studies, including biopsies and various other circulating biomarkers analyses that allow us to get smarter faster.” Many of the ongoing and recently completed trials in the kidney cancer space focused heavily on immune therapy, utilizing checkpoint-blocking antibodies like nivolumab (Opdivo) and pembrolizumab (Keytruda) or CTLA-4–blocking agents like ipilimumab (Yervoy). Of the studies moving the space forward, Jonasch highlighted an ongoing phase 1b/2 trial (NCT05501054) evaluating ipilimumab, nivolumab, and ciforadenant (CPI-444), an A2A inhibitor, in RCC along with other trials. During the discussion, Jonasch mentioned the initiative to incorporate biopsies in treatment more frequently, particularly through giving a pre- and post-biopsy to see how the results change during therapy. This approach gives investigators an opportunity to see how cancer cells interact with immune cells.  Additionally, Jonasch stated that they wish to expand their efforts to the broader kidney cancer community, as currently, work in the consortium only takes place in 7 “ivory tower” institutions that may be difficult to access for some patients. One of the ways they’re combatting this barrier is through working with the Veterans Affairs hospital system. Once that effort is complete, Jonasch hopes the consortium will be able to start helping more patient groups.  KidneyCAN is a nonprofit organization with a mission to accelerate cures for kidney cancer through education, advocacy, and research funding. You can learn more about KidneyCAN’s work here: https://kidneycan.org/ Reference Beckermann K, Rini B, Haas N, George D, Jonasch E. Phase 1b/2 trial of ipilimumab, nivolumab, and ciforadenant (INC) (adenosine A2a receptor antagonist) in first-line advanced renal cell carcinoma. Oncologist. 2023;28(suppl 1):S13–4. doi:10.1093/oncolo/oyad216.022.

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• S1 Ep146: Conducting Early Phase Trials of Promising Treatments in Neuro-Oncology

  In a conversation with CancerNetwork®, Shewetal Mehta, PhD, spoke about her research team’s focuses in moving novel brain cancer therapies down the pipeline as part of an early phase clinical trials program at the Ivy Brain Tumor Center. Mehta, the deputy director and pre-clinical core leader at the Ivy Brain Tumor Center of Barrow Neurological Institute in Phoenix, Arizona, underscored a scientifically rigorous, patient-driven philosophy that drives her team members to deliver timely answers to those with brain cancer via work in a clinical lab and a pre-clinical arm. This collaboration helps identify therapeutic agents that may demonstrate activity in the brain while determining patient populations who are suitable to enroll on clinical trials. As part of her institution’s early phase trial program, Mehta specifically highlighted work associated with a phase 0/1 clinical trial (NCT06072586) evaluating BDTX-1535, a brain-penetrant fourth-generation EGFR inhibitor, for those with recurrent high-grade glioma harboring oncogenic EGFR alterations or fusions.1 Investigators are incorporating liquid biopsy, sampling cerebrospinal fluid from patients on treatment to monitor potential evolutions or changes in brain tumors. Regarding biomarker testing, Mehta described the roles that gene sequencing and immunohistochemistry can play in identifying targetable alterations in patients with brain cancer. She mentioned vorasidenib (Voranigo), which received approval from the FDA in August 2024, as an example of a targeted therapy that may be suitable for use in patients who are found to have actionable IDH mutations. “Over the last year, we’ve seen that we were capable of not just doing these early phase clinical trials [but of entering] this phase of moving drugs into phase 3 [studies]. That’s exciting,” Mehta stated regarding her outlook on the current state of brain cancer treatment. “Right now, we are excited about these new classes of agents that are within the space, like the proteolysis targeting chimeras, protein degraders, and antibody-drug conjugates, which have shown amazing promise in the rest of the oncology space.” References 1.        Study of BDTX-1535 in recurrent high-grade glioma (HGG) participants with EGFR alterations or fusions. ClinicalTrials.gov. Updated January 15, 2025. Accessed January 15, 2025. https://tinyurl.com/m6kwr2b3 2.        FDA approves vorasidenib for grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. News release. FDA. August 6, 2024. Accessed January 20, 2025. https://tinyurl.com/25r9fkvy

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• S1 Ep145: Psilocybin May Help Address Cancer-Related Psychological Concerns

  CancerNetwork® spoke with Michael P. Bogenschutz, MD, director of the NYU Langone Center for Psychedelic Medicine and professor of Psychiatry at NYU Grossman School of Medicine, about psilocybin-assisted psychotherapy (PAP) in managing psychological challenges associated with serious cancer diagnoses following the publication of a pooled analysis of 2 phase 2 trials assessing the regimen in this patient population. In these trials, 87 patients were randomly assigned 1:1 to receive either psilocybin first (n = 45) or control therapy with niacin or low-dose psilocybin first (n = 42) followed by crossover. A total of 79 patients completed at least 1 assessment after the first dose. He began by touching upon the significance of the results, highlighting an improvement in multiple psychiatric symptoms including anxiety (P = .0049), depression (P = .0007), interpersonal sensitivity (P = .0005), obsession-compulsion (P = .0002), hostility (P = .009), and somatization (P < .0001). Then, Bogenschutz discussed the potential for PAP to reduce an unmet need for patients seeking effective medication to mitigate cancer-related psychological challenges, highlighting limitations of both antidepressants and anxiety medication in this population.  Next, Bogenschutz discussed implementing PAP into clinical practice for patients with cancer-related psychological challenges. In particular, he expressed that integration could occur through in-house operation, which may build the capacity to provide PAP within cancer centers, or through a referral system to a licensed practitioner trained to administer psilocybin.  Additionally, he described potential adverse effects associated with psilocybin use, highlighting acute mind-altering and sympathomimetic effects. He then expressed the importance of psychotherapy as a means of supplementing the use of psilocybin, which may help patients better attain positive mental health outcomes than with psilocybin alone.  He concluded by highlighting the lasting effects of psilocybin dosing, which may persist for months after a single dose, as well as areas for future research in assessing PAP. Specifically, he emphasized exploring ideal treatment parameters and the full psychopathological scope of the agent. Reference Petridis PD, Grinband J, Agin-Liebes G, et al. Psilocybin-assisted psychotherapy improves psychiatric symptoms across multiple dimensions in patients with cancer. Nat Mental Health. 2024;2:1408-1414. doi:10.1038/s44220-024-00331-0

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• S1 Ep144: SABCS 2024 Data Show ‘Great Steps Forward’ in Breast Cancer Care

  Following the 2024 San Antonio Breast Cancer Symposium (SABCS), Paolo Tarantino, MD, and Matteo Lambertini, MD, PhD, co-hosted a live X Space with CancerNetwork® and spoke about updated trial findings that may impact the breast cancer treatment paradigm. Tarantino is a clinical research fellow at Dana-Farber Cancer Institute and Harvard Medical School. Lambertini is an associate professor and consultant in medical oncology at the University of Genova – IRCCS Policlinico San Martino Hospital in Genova, Italy. Tarantino and Lambertini highlighted data from various studies that investigators presented at the Symposium, which included results on the use of treatment modalities such as antibody drug conjugates and CDK4/6 inhibitors. Some presentations of interest included the following: ·      Phase 3 DESTINY-Breast06 Trial (NCT04494425) o   Patients with hormone receptor (HR)–positive, HER2-low or HER2-ultralow metastatic breast cancer were assigned to receive fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) or physician’s choice of therapy. o   Treatment with T-DXd improved progression-free survival (PFS) among patients with a time to progression on frontline endocrine therapy of less than 6 months (HR, 0.38; 95% CI, 0.25-0.59), 6 to 12 months (HR, 0.69; 95% CI, 0.43-1.12), and more than 12 months (HR, 0.67; 95% CI, 0.51-0.88). o   PFS improved with T-DXd regardless of disease burden. ·      Phase 3 EMBER-3 Trial (NCT04975308) o   Investigators evaluated 3 treatment arms—imlunestrant (LY3484356) monotherapy, fulvestrant (Faslodex) or exemestane (Aromasin), and imlunestrant in combination with abemaciclib (Verzenio)—among patients with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer. o   Across the overall population, imlunestrant monotherapy improved PFS compared with standard endocrine therapy (HR, 0.87; 95% CI, 0.72-1.04; P = .12). o   Imlunestrant plus abemaciclib also showed a PFS improvement vs endocrine therapy across the overall population (HR, 0.57; 95% CI, 0.44-0.73; P <.001).  ·      Phase 2 SOLTI-VALENTINE Trial (NCT05569811) o   Patients with primary operable HR–positive/HER2-negative breast cancer were assigned to receive patritumab deruxtecan (HER3-DXd) alone, HER3-DXd plus letrozole (Femara), or standard multiagent chemotherapy. o   HER3-DXd monotherapy yielded a pathologic complete response (pCR) rate of 4.0% (95% CI, 0.5%-13.7%) and an objective response rate (ORR) of 70.0% (95% CI, 55.4%-82.1%); the respective rates in the chemotherapy arm were 4.2% (95% CI, 0.1%-21.1%) and 70.8% (95% CI, 48.9%-87.4%). o   Combining HER3-DXd with letrozole produced a pCR rate and ORR of 2.1% (95% CI, 0.1%-11.1%) and 81.3% (95% CI, 67.4%-91.1%), respectively.

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