Investigator Perspectives

Paul L. Swiecicki, MD, of the University of Michigan Rogel Cancer Center, discusses the rationale for dual EGFR-MET targeting with subcutaneous amivantamab, along with efficacy and safety results from the pivotal phase 1b/2 OrigAMI-4 study in recurrent/metastatic, HPV-unrelated head and neck squamous cell carcinoma after progression on an immune checkpoint inhibitor and platinum-based chemotherapy. He also reviews the design of the phase 3 OrigAMI-5 study, which evaluates amivantamab in the first-line setting.

This Targeted™ Oncology Investigator Perspectives program examines the evolving treatment landscape in multiple myeloma, with a focus on emerging evidence across newly diagnosed and relapsed/refractory disease. Dr. Peter Voorhees moderates a discussion with Dr. Doris Hansen and Dr. Luciano Costa covering frontline CD38 monoclonal antibody-based therapy, BCMA- and GPRC5D-directed bispecific antibodies, and BCMA-directed CAR T-cell therapy. The investigators review selected clinical trial data, including study rationale, design, efficacy, safety, and practical considerations for treatment implementation. The discussion also explores how newer therapies are moving into earlier lines of treatment and how patient and disease characteristics may influence therapeutic choices. In the closing panel, the faculty discuss treatment selection and sequencing between bispecific antibodies and CAR T-cell therapy, including considerations such as prior treatment exposure, disease behavior, toxicity, treatment logistics, patient preferences, and the evolving evidence base.

Ticiana Leal, MD, of Winship Cancer Institute, Emory University; Wade Iams, MD, of Tennessee Oncology; and Martin Dietrich, MD, PhD, of US Oncology, discuss how patients with ROS1-positive advanced non-small cell lung cancer are identified, how frontline therapy is chosen among the approved inhibitors, and how these agents differ in durability, intracranial activity, and tolerability.

Andrew A. Lane, MD, PhD, explores the evolving landscape of blastic plasmacytoid dendritic cell neoplasm (BPDCN). From the first CD123-targeted approvals to triplet therapy breakthroughs, Lane discusses how modern protocols are transforming patient outcomes in this rare malignancy.

An expert discusses the historic challenges associated with blastic plasmacytoid dendritic cell neoplasm (BPDCN) as a distinct disease; however, targeted therapy may offer a new treatment paradigm shift, aiding patients toward a complete response and a bridge to transplant.

An expert discusses the challenges in treating cGVHD, in particular with a focus on minimizing treatment-related toxicities. Reviewing the implementation of novel strategies in the real world setting for community oncologists, highlighting data presented at the 67th ASH Annual Meeting and Exposition.

An expert discusses the potential of antibody–drug conjugates for first-line treatment in patients with advanced triple-negative breast cancer, covering efficacy outcomes, safety data, patient-reported outcomes, and biomarker analyses from pivotal trials in this setting.

Panelists discuss how advances in combination immunotherapy and biomarker-driven strategies are redefining frontline management of advanced melanoma, improving durability of response and paving the way for more personalized treatment approaches.

An expert discusses advances in frontline treatment for patients with EGFR-mutated non–small cell lung cancer, reviewing current standards, key clinical trials, and future directions in the evolving therapeutic landscape.

A panelist discusses recent updates in the first-line treatment of metastatic triple-negative breast cancer, including new clinical trial data, emerging therapies, and the role of biomarker-guided selection in community oncology practice.

Alicia Morgans, MD, MPH, discusses how the PEACE III trial demonstrated that combining radium-223 with enzalutamide significantly improved radiographic progression-free survival and overall survival compared to enzalutamide alone in patients with metastatic castration-resistant prostate cancer who had bone metastases and limited prior treatment exposure, establishing this combination as a new standard of care when used with mandatory bone protective agents.

Panelists highlight how novel oral selective estrogen-receptor degraders SERDs and targeted therapies—guided by biomarker-driven, dynamic molecular monitoring—are transforming personalized treatment of ER-positive, HER2-negative metastatic breast cancer by improving efficacy, tolerability, and sequencing strategies to overcome resistance and enhance patient outcomes.

An expert discusses recent updates in the evolving treatment landscape of metastatic castration-resistant prostate cancer (mCRPC), highlighting new clinical trial data, emerging combination therapies, and evolving treatment selection strategies—emphasizing their implications for community oncologists aiming to balance efficacy, tolerability, and personalized care in clinical practice.

A panelist discusses how chronic graft-versus-host disease (cGVHD) affects 30-50% of allogenic transplant patients, explaining its clinical diagnosis across eight cardinal organs (particularly skin, joints, mouth and lungs), treatment approaches with corticosteroids as first-line therapy, and comparing four FDA-approved second-line agents (Ibrutinib, Belimacidil, Ruxolitinib, and Exitelimab) with their unique mechanisms of action, efficacy, and appropriate sequencing based on organ involvement.

Amandeep Salhotra, MD, discusses how chronic graft-vs-host disease (cGVHD) commonly affects transplant recipients, with risk factors including HLA mismatch and peripheral blood stem cell grafts, and how new treatments like axatilimab target the monocyte-macrophage pathway to effectively treat this condition, particularly in patients with lung involvement, while ongoing clinical trials explore both improved prophylactic strategies and corticosteroid-free interventions for moderate to severe cGVHD.

Thorvardur R. Halfdanarson, MD, discusses how neuroendocrine tumors are classified according to World Health Organization guidelines, diagnosed primarily through imaging, and treated with approaches including observation, surgery, somatostatin analogues, chemotherapy, peptide receptor radionuclide therapy, and the newly approved cabozantinib, with treatment decisions based on tumor grade, disease extent, and symptom presence.

An expert discusses recent insights from the COCOON trial, a study evaluating enhanced vs standard dermatologic management with amivantamab + lazertinib in advanced NSCLC.

Matthew Galsky, MD, discusses how recent updates in adjuvant immune checkpoint inhibition for bladder cancer emphasize the integration of agents like pembrolizumab and atezolizumab, showing improved disease-free survival post cystectomy. Ongoing trials aim to refine treatment regimens and patient selection.

Juan Pablo Alderuccio, MD, explores the evolving treatment landscape of relapsed/refractory follicular lymphoma, highlighting how novel combinations like loncastuximab tesirine plus rituximab address key therapeutic challenges through complementary targeting of CD19 and CD20, with initial evidence supporting this approach in the pursuit of improved patient outcomes.

Thomas W. LeBlanc, MD, MA, discusses how recent updates from the COMMANDS trial and advancements in anemia management, including the role of luspatercept, are shaping the treatment landscape for low-risk myelodysplastic syndromes (LR-MDS) and improving patient outcomes and quality of life.

James J. Harding, MD, discusses how emerging front-line immunotherapies, particularly the combination of nivolumab and ipilimumab, are shaping the treatment landscape for unresectable hepatocellular carcinoma (uHCC), with a focus on efficacy, safety, and patient selection.

Hope S. Rugo, MD, FASCO, provides comprehensive guidance on elacestrant’s clinical efficacy in ER+/HER2– metastatic breast cancer, including its performance in the EMERALD trial, ongoing combination studies (ELEVATE and ELECTRA), and the critical role of molecular testing and ctDNA analysis in treatment planning, while noting these data from SABCS 2024.

Hatim Husain, MD, discusses how recent updates on acquired resistance mechanisms and overall survival data for combination therapies involving amivantamab, lazertinib, and chemotherapy in EGFR-mutated NSCLC patients progressing after first-line osimertinib treatment are shaping the evolving treatment landscape and influencing clinical decision-making.

Saeed Sadeghi, MD, discusses a case of lower-risk myelodysplastic syndromes (LR-MDS), focusing on the mechanisms of action for luspatercept vs epoetin alfa, insights from the COMMANDS study, real-world data on treatment outcomes, health care resource utilization, and future directions in anemia management within this patient population.