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:
FDA Approval of Dato-DXd for Unresectable or Metastatic TNBC: Rena D. Callahan, MD
Rena D. Callahan, MD, of UCLA Health and the David Geffen School of Medicine at UCLA, highlights the significance of the May 2026 FDA approval of datopotamab deruxtecan-dlnk (Datroway; Dato-DXd) for adult patients with unresectable or metastatic triple-negative breast cancer are not candidates for PD-1/PD-L1 inhibitor therapy. The decision was supported by results from the phase 3 TROPION-Breast02 trial (NCT05374512), in which Dato-DXd led to a median overall survival (OS) of 23.7 months vs 18.7 months with chemotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .0290). Callahan noted that although patients with HER2-positive and hormone receptor–positive metastatic breast cancer often achieve OS durations of approximately 6 years, such longevity remains rare in this disease, making the integration of antibody-drug conjugates like Dato-DXd a high priority for the field. Transitioning to Dato-DXd in clinical practice requires dedicated provider and nursing education, particularly regarding ophthalmologic toxicities that necessitate collaboration with optometrists or ophthalmologists, specific eye drop protocols, regular specialty visits, and management of stomatitis. She concluded that these toxicities are manageable for most patients, and Dato-DXd represents a valuable new option for those who relapse after previous chemotherapy and immunotherapy.
Design of the MAESTRA 1 Trial in Platinum-Resistant Ovarian Cancer: Premal H. Thaker, MD, MS
Premal H. Thaker, MD, MS, of Siteman Cancer Center of Washington University in St. Louis, reviews the phase 3 MAESTRA 1 trial (NCT07023627) in platinum-resistant ovarian cancer, emphasizing that a key strength of the study is its requirement that patients have already received standard prior therapies for platinum-resistant disease, ensuring the population closely mirrors real-world clinical practice. This design eliminates retrospective uncertainty about previous treatment histories and provides greater confidence that observed efficacy outcomes are meaningful and applicable to everyday oncology care, Thaker noted. The trial also enrolls those who have undergone as many as 4 previous lines of therapy, expanding access to clinical research while generating valuable insights into treatment sequencing in a population with urgent unmet needs. She concluded that by assessing outcomes spanning lines of treatment, MAESTRA 1 aims to provide data-driven clarity on where these therapies are best suited within the disease course, potentially informing future sequencing strategies.
PSA End Points of the Phase 3 PSMAddition Study in PSMA+ mHSPC: Fred Saad, CQ, MD, FRCS, FCAHS
Fred Saad, MD, CQ, FRCS, FCAHS, of the Montreal Cancer Institute and the Université de Montréal, discusses prostate-specific antigen (PSA) end point findings from the phase 3 PSMAddition study (NCT04720157) examining lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) in prostate-specific membrane antigen–positive metastatic hormone-sensitive prostate cancer (mHSPC). PSMAddition previously met its primary end point with a statistically significant 28% reduction in the risk of radiographic disease progression (HR, 0.72; 95% CI, 0.58-0.90; P = .002), and PSA end point data presented at the 2026 American Urological Association Annual Meeting revealed that although both arms demonstrated PSA response rates exceeding 98%, meaningful differentiation emerged at deeper suppression thresholds. Achievement of PSA levels below 0.2 ng/mL up to week 48 increased from 74.9% with ADT plus ARPI (n = 394) to 87.4% with the addition of lutetium Lu 177 vipivotide tetraxetan (n = 366); at the more stringent threshold of PSA below 0.02 ng/mL, response rates rose from 46.7% to 65.3%, respectively. Saad described these findings as unprecedented in the mHSPC setting. He concluded that these data support maximizing tumor suppression as early as possible in hormone-sensitive disease, providing compelling evidence that intensified targeting translates to more durable disease control.
Key Updates to the WHO Diagnostic Criteria for AML: Sanam Loghavi, MD
Sanam Loghavi, MD, of The University of Texas MD Anderson Cancer Center, addresses recent updates to the World Health Organization (WHO) diagnostic criteria for acute myeloid leukemia (AML), focusing on the rationale behind the updates and the clinical problems they seek to resolve. She explained that the WHO 5th edition and the International Consensus Classification diagnostic criteria for AML were published around the same time, sharing many characteristics but also diverging in key areas—creating confusion in everyday clinical practice when diagnosing this disease. The forthcoming WHO 6th edition aims to harmonize these two classifications into a single unified framework while also incorporating novel data, technologies, and treatment strategies, including updates driven by recent FDA approvals such as menin inhibitors for select patients with relapsed/refractory AML. Loghavi concluded that understanding the underlying genetic profile of disease is essential in this evolving landscape, as determining eligibility for menin inhibition requires precise molecular characterization.
Treatment Navigation in R/R Mantle Cell Lymphoma: Tycel Phillips, MD
Tycel Phillips, MD, of City of Hope, examines treatment considerations for relapsed/refractory mantle cell lymphoma (MCL) after covalent BTK inhibitor–based therapy. He noted that although bispecific antibodies are not currently approved by the FDA in MCL and remain inconsistently accessible, particularly in community settings, they are generating increasing interest due to their favorable logistical profile and potentially lower toxicity burden relative to CAR T-cell therapy. The latter modality remains a preferred option for eligible patients given its ability to induce deeper and more durable remissions, and the noncovalent BTK inhibitor pirtobrutinib (Jaypirca) serves as an effective bridging strategy, although long-term disease control is not expected for the majority of patients. Phillips noted that updated findings from a phase 1/2 trial (NCT03075696) examining glofitamab-gxgm (Columvi) monotherapy will be presented at the 2026 ASCO Annual Meeting, and that if a bispecific antibody gains regulatory approval in MCL, it may move earlier in the treatment algorithm given its ease of administration and broader accessibility vs brexucabtagene autoleucel (Tecartus). He concluded that although neither bispecific antibodies nor CAR T-cell therapy is considered curative in this disease, ongoing follow-up will be critical to determine whether bispecific antibody responses are sufficiently durable to position them alongside CAR T-cell therapy as long-term disease control strategies.
