OncLive News Network®

In this OncLive News Network program, Julio C. Chavez, MD, of Mayo Clinic in Jacksonville, Florida, and Tycel Phillips, MD, of City of Hope in Duarte, California, discuss the evolving treatment landscape for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in the third-line setting and beyond. The physicians review available options and unmet needs, particularly for patients with CAR T-refractory disease, before focusing on the bispecific antibodies epcoritamab and glofitamab. They examine pivotal efficacy and safety data, the differences between continuous and fixed-duration treatment, and subcutaneous versus intravenous administration. They also share practical strategies for managing cytokine release syndrome in the outpatient setting, preventing infections, and monitoring immune recovery. The discussion then turns to patient selection, emerging bispecific-based combinations, and potential use in earlier lines of therapy. They close with key takeaways for community oncologists integrating bispecific antibodies into practice.

In this OncLive News Network program, Allan Lima Pereira, MD, of Moffitt Cancer Center, and Sunnie Kim, MD, of University of Colorado Cancer Center, discuss first-line treatment for HER2-positive gastroesophageal adenocarcinoma (GEA) following the pivotal HERIZON-GEA-01 trial and the FDA approval of zanidatamab-based regimens. The physicians trace the evolution of the first-line landscape from the ToGA and KEYNOTE-811 trials and review the design and efficacy results of HERIZON-GEA-01. They also examine how HER2 expression shapes the FDA-approved indications. They explore the unexpected PD-L1 subgroup findings, the rationale for adding tislelizumab, and practical strategies for preventing and managing diarrhea, including how to distinguish it from immune-mediated colitis. The discussion closes with guidance on selecting between the zanidatamab and KEYNOTE-811 regimens, the importance of comprehensive biomarker testing, and how to prioritize HER2-directed therapy when multiple biomarkers are positive.

This OncLive News Network program explores evolving treatment strategies for patients with HER2-positive early breast cancer, with a focus on translating emerging clinical trial evidence into clinical practice. Dr. Ruta Rao and Dr. Jason Mouabbi discuss the current treatment continuum from neoadjuvant therapy through surgery and post-neoadjuvant treatment, including the role of pathologic response in guiding subsequent management. They review findings from the DESTINY-Breast11 trial and consider how its high-risk study population relates to the broader FDA-approved neoadjuvant indication and current NCCN recommendations. The discussion then moves to the post-neoadjuvant setting, comparing the high-risk population and findings from DESTINY-Breast05 with the established evidence from KATHERINE, including considerations for T-DXd and T-DM1 selection. Dr. Rao and Dr. Mouabbi also discuss treatment sequencing, individual patient selection, and practical considerations surrounding T-DXd-associated interstitial lung disease, emphasizing the importance of monitoring and multidisciplinary coordination when treating HER2-positive early breast cancer.

OncLive® will be premiering OncLive® News Network: On Location at the International Association for the Study of Lung Cancer 2026 World Conference on Lung Cancer! Each day, we will broadcast a series of interviews with top thought leaders, to learn their thoughts and reactions to data presented across thoracic oncology during the conference.

Danielle M. Brander, MD, of Duke University School of Medicine, and Marc J. Braunstein, MD, PhD, of NYU Grossman Long Island School of Medicine, examine infection as a leading competing risk in chronic lymphocytic leukemia (CLL). They review registry data showing nearly half of patients develop a serious infection and infection contributes to almost a third of deaths, the immune defects intrinsic to CLL, and the 6-to-12-month window of vulnerability after fixed-duration therapy ends. They compare infection rates across AMPLIFY (serious or grade 3 or higher infection in 14% with acalabrutinib plus venetoclax vs 25% with the triplet adding obinutuzumab), ELEVATE-TN, and CLL14 (grade 3 or 4 infection in 17.5% vs 15%), and note similar serious infection rates near 30% across BTK inhibitors in ELEVATE-RR and ALPINE. Dr Braunstein favors continuous therapy for unmutated IGHV and TP53-aberrant disease and urges counseling patients that infection is the key risk of chemotherapy-free regimens.

In this OncLive News Network program, Dr Nicole Balmaceda, a gastrointestinal medical oncologist at MD Anderson Cancer Center, and Dr Jonathan Lee, a gastrointestinal medical oncologist at Stanford University, work through a patient case of metastatic pancreatic ductal adenocarcinoma from molecular findings to treatment decision. They review a genomic report showing a KRAS mutation with a co-occurring TP53 alteration, microsatellite stable disease, and low tumor mutational burden, and explain why immunotherapy is unlikely to benefit that patient. Dr Balmaceda describes how mutated KRAS stays locked in its active state, and Dr Lee explains how to read specific alleles on a next-generation sequencing report and why allele identity carries prognostic and therapeutic weight. Both urge comprehensive sequencing at diagnosis, using tissue and liquid biopsy together. The discussion closes on the US Food and Drug Administration approval of daraxonrasib, the first pan-RAS targeted therapy in metastatic pancreatic cancer, and the trials, vaccines, and resistance questions that follow it.

Watch more on OncLive Biomarker Consortium!

This OncLive® NewsNetwork Presents program explores contemporary treatment strategies for patients with advanced renal cell carcinoma (RCC), with emphasis on individualized first-line treatment selection across clear cell and non-clear cell disease. Dr. Martin Voss and Dr. Michael Serzan discuss how histology, tumor biology, disease burden, clinical presentation, treatment goals, and patient-specific factors influence selection among immune checkpoint inhibitor and tyrosine kinase inhibitor-based regimens. The experts examine the importance of achieving early, deep, and durable responses, including the potential role of treatment de-escalation or consolidative approaches in selected patients with favorable responses. The discussion also addresses emerging evidence in non-clear cell RCC, including papillary, chromophobe, and FH-deficient disease, as well as treatment considerations following progression on immunotherapy. Finally, they review evolving evidence for subsequent-line therapies, including combination approaches and HIF-2α inhibition, while considering efficacy, toxicity, quality of life, and the role of ongoing clinical research in refining treatment sequencing.

This program explores the evolving treatment landscape for primary CNS lymphoma (PCNSL), with a focus on the clinical rationale, real-world experience, and emerging role of Bruton tyrosine kinase (BTK) inhibition. Dr. Lakshmi Nayak moderates a discussion with Dr. Christian Grommes, Dr. Motoo Nagane, and Dr. Jerome Cheng, bringing together perspectives from the United States, Japan, and Taiwan. The discussion reviews the biological features of PCNSL that support BTK inhibition, including frequent alterations affecting the B-cell receptor signaling pathway, as well as the challenges of treating disease within the central nervous system. Faculty discuss the evolution of BTK inhibitors, clinical trial findings, CNS penetration, treatment selection, response and durability, and practical management of adverse events. Dr. Nagane and Dr. Cheng provide insights from clinical practice in Japan and Taiwan, where tirabrutinib is approved for relapsed/refractory PCNSL. The faculty also consider opportunities for BTK inhibitors in combination and earlier-line settings, while highlighting remaining questions regarding durability and long-term disease control. The program is intended to provide an international perspective on the role of BTK inhibition in PCNSL.

This OncLive News Network program brings together two specialists for a discussion of how second-line treatment for KIT-mutant gastrointestinal stromal tumor (GIST) may be changing. The panelists talk through why treatment becomes harder after first-line therapy stops working, and what the biology of resistance means for the way clinicians choose and sequence agents. They review emerging data on a combination approach that adds an investigational agent to the current second-line standard rather than replacing it, discussing what the results showed on efficacy and on tolerability, and how the combination compares with what has been achievable in this setting until now. The conversation then turns to where things stand from a regulatory standpoint, how such a regimen would fit alongside the therapies already in use, the role of mutation testing in guiding decisions, and where the panelists agree and differ on managing patients today.

Two thoracic medical oncologists review how poor prognostic factors shape frontline treatment selection in EGFR-mutated advanced non-small cell lung cancer (NSCLC) and place data from the TOP study, FLAURA2 study, and FLAME trialinto practice context.

Gino K. In, MD, MPH, and Lara A. Dunn, MD, review updated long-term follow-up data on cosibelimab from the CK-301-101 study and discuss what its efficacy, durability, and tolerability mean for patients with locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or radiation.

Dr. Lewis Silverman from Columbia University Irving Medical Center and Dr. Emily Curran from the University of Cincinnati discuss pediatric-inspired asparaginase-based regimens for adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL), with a focus on the 2026 ASH guidelines for frontline ALL management in AYAs and the comprehensive expert consensus published in Haematologica on asparaginase adverse event management.

The discussion addresses why pediatric-inspired regimens represent the standard of care for AYA ALL, barriers to real-world adoption including regimen complexity and asparaginase hesitancy, and the key adverse events that drive unnecessary discontinuation: hepatotoxicity, thrombosis, pancreatitis, and hypersensitivity. Therapeutic drug monitoring including asparaginase enzyme activity measurement, dose capping and empiric dose reduction strategies, pegaspargase premedication, and the critical distinction between true hypersensitivity and silent inactivation are discussed in depth. Experts describe practical management and the importance of managing through adverse events rather than discontinuing effective therapy.

In this OncLive Medical News Network discussion, two melanoma experts explore how emerging real-world evidence is reshaping the management of unresectable and metastatic melanoma. The conversation centers on tumor-infiltrating lymphocyte therapy, a one-time cellular treatment now available for patients whose disease has progressed on checkpoint inhibitors and other standard-of-care options. The faculty examine where this therapy fits within the broader treatment landscape, offering eligible patients a meaningful chance at durable, long-term remission. Drawing on recent multicenter and single-center retrospective analyses, they discuss how real-world outcomes are validating pivotal trial findings across a broader patient population, with no new safety signals identified. The discussion offers practical, experience-driven insight into patient selection, the importance of earlier referral, the treatment journey from tumor procurement through recovery, safety management, and individualized approaches to IL-2 dosing. Throughout, the experts emphasize thoughtful sequencing and timely referral to optimize patient outcomes.

In this OncLive® News Network program, Dr. Jason Mouabbi and Dr. Seth Wander discuss evolving strategies for the management of HR-positive, HER2-negative advanced breast cancer, with a focus on the emerging role of ESR1 mutation detection and endocrine resistance. The discussion explores current treatment approaches with endocrine therapy and CDK4/6 inhibition, the clinical significance of ESR1 mutations as markers of acquired resistance, and the potential role of ctDNA-based monitoring in identifying resistance mechanisms before radiographic progression. Dr. Mouabbi and Dr. Wander review the rationale behind earlier therapeutic intervention, treatment sequencing considerations, and emerging clinical evidence evaluating endocrine therapy modification strategies, including data from key studies such as PADA-1, SERENA-6, EMERALD, and EMBER-3. The experts also discuss practical considerations for integrating biomarker testing into clinical practice, patient-centered factors such as quality of life and treatment tolerability, and future directions toward more individualized, biomarker-guided care for patients with HR-positive, HER2-negative advanced breast cancer.

Dr. Ticiana Leal, professor and director of the Thoracic Program at the Winship Cancer Institute of Emory University, presents a single-expert discussion on treatment selection and sequencing for patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC), focusing on data presented at ELCC 2026.

The discussion covers frontline decision-making between osimertinib monotherapy, osimertinib plus chemotherapy (FLAURA2), and amivantamab plus lazertinib (MARIPOSA), with updated overall survival data favoring combination strategies for the majority of patients harboring high-risk features. Key topics include TP53 co-mutation and ctDNA-driven risk stratification, new TOP trial data, real-world toxicity management including the COCOON dermatologic prophylaxis strategy, the shift to subcutaneous amivantamab, time toxicity considerations, second-line sequencing including COMPEL, MARIPOSA-2, and datopotamab deruxtecan, chemotherapy rechallenge data from FLAURA2, and CNS and leptomeningeal disease management. Dr. Leal closes with anticipated developments in early-stage and perioperative EGFR-mutated NSCLC treatment.

Dr. Seema Nagpal, clinical professor of neurology in the Division of Neuro-oncology at Stanford University, and Dr. Laura Alder, assistant professor of thoracic medical oncology at Duke University, discuss CNS disease management in EGFR-mutated non-small cell lung cancer (NSCLC).

The program covers first-line CNS efficacy data from the FLAURA2 and MARIPOSA trials, CNS surveillance standards and barriers to consistent practice, a clinical case of CNS-only progression on osimertinib, second-line sequencing across COMPEL, TROPION-Lung01 and TROPION-Lung05, and MARIPOSA-2, and emerging agents including datopotamab deruxtecan, ivonesimab, and izalontamab brengitecan. Critical gaps in CNS endpoint reporting, including treated versus untreated lesions, leptomeningeal disease inclusion, response criteria heterogeneity, are examined. Leptomeningeal disease management is discussed in depth, including osimertinib dose escalation and pulse dosing, amivantamab-lazertinib sequencing, intrathecal therapies, proton craniospinal irradiation, and cerebrospinal fluid liquid biopsy including circulating tumor cells. Strategies for community clinicians without access to specialized interventions are emphasized throughout.

Dr. Estelamari Rodriguez and Dr. Coral Olazagasti from the University of Miami discuss the groundbreaking TOP study, which provided the first prospective phase 3 evidence for treatment intensification in patients with EGFR-mutant non-small cell lung cancer harboring concurrent TP53 mutations.

The TOP study demonstrated remarkable benefits for osimertinib plus chemotherapy versus osimertinib alone in TP53-mutant patients, with median progression-free survival improving from 15.6 to 34 month, more than doubling survival outcomes. This represents an 18-month absolute gain, exceeding the average benefit observed in FLAURA2 for the entire population.

The discussion contextualizes these findings within the broader treatment landscape, comparing FLAURA2 and MARIPOSA regimens while addressing practical considerations for patient selection. Key topics include risk stratification beyond TP53 (including L858R mutations and central nervous system involvement), shared decision-making approaches, and sequencing strategies following first-line combination therapy.

Through clinical scenario-based discussions, the panelists emphasize that combination therapy should represent the new standard of care for most patients, with TP53 status providing additional confirmation for treatment intensification rather than serving as the sole decision-making factor.

Two lymphoma experts discuss how duvelisib, supported by the PRIMO study and the ongoing TERZO phase 3 trial, is reshaping the treatment of relapsed/refractory peripheral T-cell lymphoma.

Dr. Mrinal Gounder led a comprehensive discussion with Drs. Atrayee Basu Mallick and Nam Bui on evolving treatment strategies for desmoid tumors. The program highlighted the paradigm shift from surgical intervention to multimodal approaches emphasizing active surveillance and systemic therapies.

Key topics included patient selection criteria for watchful waiting versus treatment initiation, considering factors such as tumor location, size, symptoms, and growth trajectory. High-risk locations include head/neck, mesenteric areas, and proximity to neurovascular structures. The discussion emphasized moving away from surgery due to high recurrence rates and significant morbidity, particularly in challenging anatomical locations.

The RINGSIDE trial presented at ASCO 2026 demonstrated impressive efficacy for varagesestat, a once-daily gamma-secretase inhibitor, with an 84% reduction in progression risk and rapid pain relief within 4 weeks. This adds to the therapeutic armamentarium alongside nirogacestat, the first FDA-approved treatment.

Unmet needs include determining optimal treatment duration, understanding mechanisms of spontaneous regression in 20% of patients, managing fertility concerns in predominantly young female populations, and developing predictive biomarkers for treatment selection.

Dr. Jonathan Strosberg from Moffitt Cancer Center discussed the challenging landscape of extrapulmonary neuroendocrine carcinoma (NEC), a rare and aggressive malignancy distinct from well-differentiated neuroendocrine tumors. Through a case of a 64-year-old man with metastatic colonic NEC, Dr. Strosberg highlighted key diagnostic challenges and treatment limitations in this historically underappreciated disease.

Poorly differentiated NECs demonstrate high Ki-67 proliferation indices (>55%), aggressive histology with necrosis and pleomorphism, and distinct mutational patterns including p53 and RB1 alterations similar to small cell lung cancer. Traditional platinum-based chemotherapy yields poor outcomes, with median progression-free survival of 2 to 6 months in second-line settings.

DLL3 emerges as a promising therapeutic target, expressed in approximately 75% of extrapulmonary NECs. Bispecific T-cell engagers like tarlatamab targeting DLL3 show encouraging activity in patients with high DLL3 expression (>50%), achieving approximately 40% response rates versus 3% in low expressors.

Vasomotor symptoms (VMS) are among the most clinically consequential adverse events of endocrine therapy in patients with hormone receptor–positive breast cancer, affecting the majority of treated patients and contributing to suboptimal treatment adherence. In this video series, Carmine Valenza, MD, MPH, PhD(c), reviews the neurobiology underlying VMS, explaining how estrogen deprivation leads to hyperactivation of hypothalamic KNDy neurons and how dual NK1/NK3 receptor antagonism with elinzanetant (Lynkuet) targets this pathway through a nonhormonal mechanism considered safe for use in patients with breast cancer.

The phase 2 ARASEC trial (NCT02799602) evaluated darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in the United States, utilizing an innovative synthetic historical control design derived from the prospective, randomized phase 3 CHAARTED trial (NCT00309985). Neal D. Shore, MD, FACS, and Rana R. McKay, MD, FASCO, co-led the trial, which met its primary end point of radiographic progression-free survival, with an HR of 0.29 compared with the ADT monotherapy control arm, and demonstrated a statistically significant overall survival benefit (HR, 0.50). In this Investigator Perspectives program, Shore and McKay explore design, key findings, and significance of ARASEC.

The Moonlight Shift, with host Gina Mauro, features leading and early-career oncologists from the Tri-State corridor in peer-level conversations about where the field is going — and what it still has to work out.

Dr. Edwin Choy from the sarcoma oncology program and Dr. Sarah Bouberhan from gynecologic medical oncology at Massachusetts General Hospital discussed perivascular epithelioid cell tumors (PEComas), rare mesenchymal neoplasms affecting approximately 75% of patients with benign or uncertain malignant potential. PEComas occur predominantly in women aged 20 to 55 years, commonly affecting the uterus, kidney, retroperitoneum, gastrointestinal tract, liver, and lungs. Diagnosis requires expert pathological evaluation with specific immunohistochemical markers including melanocytic markers (HMB-45, Melan-A) and smooth muscle markers (SMA, desmin, caldesmon).

Molecular characterization reveals approximately 50% harbor TSC1 or TSC2 loss affecting mTOR pathway signaling, whereas others demonstrate TFE3 gene rearrangements. The AMPECT phase 2 trial established nab-sirolimus as FDA-approved first-line therapy for advanced disease, demonstrating 39% response rates with 10.6-month progression-free survival and 40.8-month overall survival. Patients with TSC2 mutations showed nearly 90% response rates versus 13% for non-TSC2 mutations.

Dr. Megan Melody from Tampa General Hospital Cancer Institute and Dr. Mark Roschewski from Memorial Sloan Kettering Cancer Center discussed how circulating tumor DNA (ctDNA) testing is transforming lymphoma care through enhanced risk stratification, treatment monitoring, and personalized patient management.

Key insights emphasized ctDNA as an emerging risk factor superior to baseline assessments, with most patients achieving undetectable levels after 2 cycles. Combined negative positron emission tomography and ctDNA results reduce relapse risk from 15% to 20% to single digits. However, ctDNA currently serves as a prognostic marker rather than treatment-guiding tool, with ongoing ALPHA3 trial investigating ctDNA-guided therapy using allogeneic CAR-T cells.

Clinical Implementation:

• Seventy-five percent concordance between ctDNA and PET imaging results

• Serial testing preferred over single time-point assessments for surveillance

• Technology varies across lymphoma subtypes, with phased variant assays showing superior sensitivity

• Quantitative values enable kinetic monitoring for individual patients with baseline controls

Dr. Helena Yu of Memorial Sloan Kettering Cancer Center and Dr. Sonam Puri of Moffitt Cancer Center discuss the phase 3 TOP study, presented at the European Lung Cancer Congress (ELCC) 2026, which evaluated osimertinib plus carboplatin/pemetrexed versus osimertinib monotherapy in non–small cell lung cancer (NSCLC) patients with EGFR mutations and concurrent TP53 alterations. The study showed a median progression-free survival (PFS) of 34.0 versus 15.6 months (hazard ratio [HR], 0.44), with consistent benefit across subgroups including central nervous system (CNS) and liver metastases. The experts contextualize TOP within FLAURA2 and MARIPOSA, address patient selection beyond TP53, walk through safety and toxicity management for combination regimens, and outline sequencing strategies at progression. They close with practical guidance for community oncologists and unanswered questions, including the role of circulating tumor DNA (ctDNA) dynamics as an emerging predictive biomarker.

Dr. Pedro Barata and Dr. Johann De Bono discuss recent advances in metastatic castration-resistant prostate cancer, with a focus on the evolving role of radiopharmaceuticals across the treatment landscape. They review key clinical updates from recent meetings, including emerging data on both established therapies and next-generation PSMA-targeted approaches, and examine how these findings are shaping treatment selection and sequencing strategies.

Dr. Mazyar Shadman from the University of Washington/Fred Hutchinson Cancer Center and Dr. Danielle Brander from Duke Cancer Institute discuss matching adjusted indirect comparisons (MIACs) for first-line chronic lymphocytic leukemia (CLL) treatment decisions. The discussion explores how these statistical methodologies help compare treatments from different clinical trials when direct head-to-head comparisons are unavailable, acknowledging their limitations while recognizing their value in rapidly evolving treatment landscapes.

Key analyses include zanubrutinib (SEQUIOA trial) comparisons with venetoclax-based fixed-duration regimens, CLL14 (venetoclax-obinutuzumab), and AMPLIFY (acalabrutinib-venetoclax). Results consistently favored continuous BTK inhibitor therapy for progression-free survival, particularly after 3 years, while demonstrating favorable safety profiles despite longer treatment exposure.

Clinical Considerations:

• MIACs provide systematic comparisons beyond separate trial evaluations but cannot replace randomized head-to-head trials
• Anchored analyses (shared control arms) offer stronger evidence than unanchored methodologies
• Patient goals regarding treatment duration, efficacy priorities, and risk tolerance remain paramount in decision-making
• Disease markers including IGHV mutation status and TP53 aberrations influence optimal treatment selection between continuous versus fixed-duration approaches

A panel of exerts focus on the management of advanced renal cell carcinoma, emphasizing why the first-line treatment decision is the most critical opportunity to influence patient outcomes. This initial treatment decision can shape the entire patient journey and remains central to achieving optimal outcomes. Experts explore the importance of early and effective disease control, including how tumor biology, disease burden, and patient fitness shape treatment selection and prognosis. We’ll also discuss key clinical considerations and real-world patterns, including the fact that some patients may not receive subsequent therapy. Finally, they will review emerging clinical data and consider how these insights can be applied to optimize outcomes for the patient in front of us.