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 Post-Neoadjuvant T-DXd for HER2+ Breast Cancer: Charles E. Geyer, MD
Charles E. Geyer, MD, of the University of Pittsburgh and the University of Pittsburgh Medical Center Hillman Cancer Center, details the significance of the May 15, 2026 FDA approval of post-neoadjuvant fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for the treatment of adult patients with HER2-positive breast cancer who have residual invasive disease after neoadjuvant HER2-directed treatment. The decision was supported by data from the phase 3 DESTINY-Breast05 trial (NCT04622319), in which patients receiving T-DXd (n = 818) achieved a 3-year invasive disease-free survival (iDFS) rate of 92.4% (95% CI, 89.7%-94.4%) vs 83.7% (95% CI, 80.2%-86.7%) with ado-trastuzumab emtansine (Kadcyla; T-DM1; n = 817; HR, 0.47; 95% CI, 0.34-0.66; P < .0001), representing a 53% reduction in recurrence risk. The data also showed early evidence suggesting T-DXd may help prevent some brain metastases, he said; however, diligent monitoring with chest CT scans was central to safe administration, and 3 patients died from interstitial lung disease (ILD) during the trial. Geyer noted that a key question surrounding the decision concerned the breadth of the indication—whether it would be confined to the highest-risk patients or extended to those with a recurrence risk of approximately 15% to 20% over 7 to 8 years who were excluded from the trial. The indication ultimately encompasses all patients with residual invasive cancer, representing a broader population than the trial itself, which Geyer characterized as reflective of the strength of the data and the trial's design.
Key Findings From the Phase 2/3 OptimUM-02 Trial in Uveal Melanoma: Marlana M. Orloff, MD
Marlana M. Orloff, MD, of Thomas Jefferson University and Jefferson Health, reviews data presented at the 2026 ASCO Annual Meeting from the phase 2/3 OptimUM-02 trial (NCT05987332) examining darovasertib plus crizotinib (Xalkori) in patients with HLA-A*02:01–negative metastatic uveal melanoma. In the randomized phase 2b portion, darovasertib plus crizotinib achieved a median progression-free survival (PFS) of 6.9 months (95% CI, 5.6-8.3) vs 3.1 months (95% CI, 1.8-4.2) with investigator's choice of therapy—which included pembrolizumab (Keytruda) monotherapy, nivolumab (Opdivo) plus ipilimumab, or dacarbazine—meeting the trial's primary end point. Secondary end points, which included overall response rate (ORR) and disease control rate (DCR), also favored the investigational arm. The most common adverse effects (AEs) with darovasertib plus crizotinib were diarrhea, nausea, vomiting, peripheral edema, and rash, managed with antidiarrheals, octreotide (Sandostatin) in refractory cases, high-fat or high-protein meals, antiemetics, and diuretics, respectively.
Strategic Timing and Concordance of Biopsies in CRC: Marwan G. Fakih, MD
Marwan G. Fakih, MD, of City of Hope, underscores why liquid biopsies should be performed at diagnosis in patients with metastatic colorectal cancer (CRC) to avoid uninformative results after chemotherapy begins, presenting illustrative case studies on the concordance of liquid and tissue biopsy at the 11th Annual School of Gastrointestinal Oncology. When chemotherapy is initiated before tissue next-generation sequencing (NGS) results are available, circulating tumor DNA (ctDNA) shedding decreases if the tumor responds, often rendering liquid biopsy uninformative, while repeat tissue biopsy on a responding tumor frequently yields necrotic tissue—leaving clinicians without actionable genomic insights until disease progression. Fakih highlighted that discordance between liquid and tissue samples can arise from tumor heterogeneity, noting that a patient may harbor both a KRAS G12C and a more dominant KRAS G12V mutation in ctDNA, the latter of which would predict lack of benefit from a G12C inhibitor like sotorasib (Lumakras). He concluded that strategic coordination of both biopsy modalities is essential for accurately interpreting the tumor's genetic landscape and delivering the most effective personalized therapy.
Investigation of Cemsidomide in Multiple Myeloma: Sikander Ailawadhi, MD
Sikander Ailawadhi, MD, of the Mayo Clinic Comprehensive Cancer Center, examines the evolving development landscape of investigational cereblon E3 ligase modulators (CELMoDs) and IKZF1 degraders for relapsed/refractory multiple myeloma. Iberdomide, mezigdomide, and cemsidomide are each establishing distinct niches based on the patient populations and treatment settings in which they are being studied. Iberdomide has generated the most mature data in earlier lines of therapy, and mezigdomide has primarily been studied in more heavily pretreated populations; cemsidomide, an investigational oral IKZF1 degrader, remains in earlier-stage development, currently being examined with dexamethasone and in combination with bispecific antibodies. Updated findings from the phase 1/2 CFT7455-1101 trial (NCT04756726) presented at the 2026 EHA Congress indicated that cemsidomide plus dexamethasone elicited an overall response rate (ORR) of 36% across all doses (n = 72) in patients with at least 3 prior lines of therapy, rising to 53% with a clinical benefit rate (CBR) of 63% at the 100 µg per day dose (n = 19). Ailawadhi concluded that continued examination across combination strategies and varying lines of therapy will be critical to clarifying the optimal roles of these agents as the therapeutic armamentarium for relapsed/refractory multiple myeloma expands.
Strengths vs Limitations of a Prospective Study of ctDNA in Osteosarcoma MRD Surveillance: R. Lor Randall, MD, FACS
R. Lor Randall, MD, FACS, of UC Davis Comprehensive Cancer Center, highlights the clinical implications of a landmark prospective longitudinal study investigating personalized circulating tumor DNA (ctDNA) panels for relapse detection in osteosarcoma. The study confirmed that post-operative ctDNA status is a statistically significant predictor of event-free survival (EFS), with negative results correlating with significantly improved outcomes (P < .05). Randall identified key strengths of the study—including one of the largest tumor-informed ctDNA cohorts reported in osteosarcoma, a prospective longitudinal sampling strategy enabling molecular tracking across the full treatment and surveillance continuum, and a personalized assay design well-suited to the marked genomic heterogeneity of this disease. However, he acknowledged important limitations, including the single-center design, short median follow-up of just over 8 months, and imperfect assay sensitivity, as some patients experienced relapse despite negative ctDNA results. Randall concluded that although the technology shows promise, the critical unanswered question—whether earlier detection ultimately improves survival, quality of life, or treatment effectiveness—must be resolved before personalized ctDNA panels can be fully integrated into standard practice.
