Welcome to The Five Under 5, your go-to roundup of the top 5 videos of the week.

These short videos are designed for busy oncologists to view on the go, and feature expert insights on breaking news, regulatory updates, practice-changing data shared at medical meetings, and other key topics in the realm of oncology.

Here’s what you may have missed:

Evolving Landscape of ADCs in HER2+ Breast Cancer: Yuan Yuan, MD, PhD

Yuan Yuan, MD, PhD, of Cedars-Sinai Medical Center and UCLA, discusses the rapidly expanding role of antibody-drug conjugates (ADCs) in breast cancer treatment as highlighted during an OncLive State of the Science Summit. She explained that beyond established HER2- and TROP2-directed drugs like sacituzumab govitecan-hziy (Trodelvy) and fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd), supported by trials like DESTINY-Breast04 (NCT04556773) and DESTINY-Breast06 (NCT04494425), newer strategies, including HER3-targeted agents and novel payload designs, are emerging. Yuan underscored the need for diversification in ADC payloads, noting that agents like datopotamab deruxtecan (Datroway) share topoisomerase I inhibitor payloads with existing ADCs, which may contribute to cross-resistance. She concluded that ADCs are now firmly established in metastatic breast cancer and are poised to expand into earlier-line treatment settings.

OS Outcomes With Darovasertib Plus Crizotinib in Metastatic Uveal Melanoma: Marlana M. Orloff, MD

Marlana Orloff, MD, of Sidney Kimmel Medical College of Thomas Jefferson University, discusses data from the phase 1/2 OptimUM-01 trial (NCT03947385) examining darovasertib plus crizotinib (Xalkori) in patients with metastatic uveal melanoma. She explained that the historical median overall survival (OS) for those with metastatic disease, particularly those with hepatic involvement, was often less than 6 months, although modern liver-directed approaches and improved MRI surveillance have contributed to longer outcomes. Orloff noted that current goals aim to extend median OS beyond 2 years, and drugs like darovasertib could help achieve this, with OptimUM-01 reporting a median OS of 21.1 months. She highlighted that the regimen has also elicited an overall response rate of 34.1%, which far exceeds the single-digit response rates typically reported with systemic therapies in this setting.

Role of Radioligand Therapy in Prostate Cancer Management: Daniel J. George, MD

Daniel J. George, MD, of Duke University School of Medicine and Duke Cancer Institute, discusses the expanding role of Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) across the prostate cancer paradigm, from hormone-sensitive disease to chemotherapy-refractory castration-resistant disease. He explained that as this radioligand therapy moves into earlier settings, much like previous androgen receptor pathway inhibitors (ARPIs), the traditional emphasis on OS becomes less relevant because outcomes are influenced by multiple confounding factors. Instead, George spotlighted growing enthusiasm for achieving minimal residual disease (MRD), which more closely aligns with patient goals such as the ability to discontinue therapy. He added that future approaches could involve leveraging radioligand therapies in various sequences or combinations to maximize the number of patients who achieve MRD negativity and potentially pause treatment, improving overall quality of life.

Safety Profile of Lutetium Lu 177 Vipivotide Tetraxetan Plus ARPI and ADT in PSMA+ mHSPC: Scott T. Tagawa, MD

Scott T. Tagawa, MD, MS, FACP, FASCO, of Weill Cornell Medicine and NewYork-Presbyterian – Weill Cornell Medical Center, discusses safety data from the phase 3 PSMAddition trial (NCT04720157) examining an ARPI plus androgen deprivation therapy with or without lutetium Lu 177 vipivotide tetraxetan in patients with prostate-specific membrane antigen (PSMA)–positive metastatic hormone-sensitive prostate cancer. He explained that because this is the third phase 3 study of this drug, the toxicity profile was unsurprising and consistent with prior experience. Dry mouth, fatigue, and nausea represented the most common treatment-related adverse effects (AEs) tied to normal PSMA-expressing tissues. Tagawa noted that hormonal AEs like hot flush and hypertension were more frequent in the control arm, and high-grade cytopenias with lutetium Lu 177 vipivotide tetraxetan were rare. He added that rates of serious AEs, treatment discontinuation, and deaths were similar between the treatment arms. No deaths were attributed to study treatment, underscoring a well-characterized and manageable safety profile.

How the PERSEUS Study Informed the ATLAS Trial in Multiple Myeloma: Andrzej Jakubowiak, MD, PhD

Andrzej Jakubowiak, MD, PhD, of the University of Chicago Medicine, discusses data from the phase 3 PERSEUS trial (NCT03710603) and how they informed the rationale for the phase 3 ATLAS study (NCT02659293) assessing carfilzomib (Kyprolis) plus lenalidomide (Revlimid) and dexamethasone (KRd) after autologous stem cell transplantation in patients with newly diagnosed multiple myeloma. He explained that PERSEUS showcased a significant progression-free survival (PFS) benefit when daratumumab (Darzalex) was added to induction and consolidation bortezomib (Velcade) plus Rd (VRd) vs VRd alone, with estimated 48-month PFS rates of 84.3% vs 67.7%. However, the specific contribution of post-transplant daratumumab plus lenalidomide maintenance could not be isolated from the rest of the regimen. Jakubowiak noted that although daratumumab plus lenalidomide has been widely adopted in maintenance therapy, it has not been directly compared with standard-of-care lenalidomide. He emphasized that the ATLAS trial is designed to address this knowledge gap by comparing the KRd investigational arm with SOC lenalidomide maintenance, thus providing clearer insight into optimal post-transplant strategies.