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 Adjuvant Belzutifan Plus Pembrolizumab in ccRCC: Toni Choueiri, MD
Toni Choueiri, MD, of Dana-Farber Cancer Institute and Harvard Medical School, unpacks the significance of the June 2026 FDA approval of adjuvant belzutifan (Welireg) plus pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) for use in adult patients with clear cell renal cell carcinoma (ccRCC) at intermediate-high or high risk of recurrence following nephrectomy, supported by results from the phase 3 LITESPARK-022 trial (NCT05239728). Building on the 2021 approval of pembrolizumab, which ended a near 5-decade wait for an effective adjuvant treatment in high-risk RCC, LITESPARK-022 examined whether adding belzutifan could further improve outcomes. The trial met its primary end point of disease-free survival (DFS), showcasing a significant benefit over placebo plus pembrolizumab (HR, 0.72; 95% CI, 0.59-0.87; P = .0003); the median DFS was not reached in either arm. Overall survival data remained immature at the protocol prespecified interim analysis. Choueiri concluded that these positive results offer the potential to further improve long-term outcomes for patients with high-risk ccRCC after surgical resection.
Effects of Depth of Response on T-DXd/Pertuzumab Treatment Outcomes in DESTINY-Breast09: Sara M. Tolaney, MD, MPH
Sara M. Tolaney, MD, MPH, of Dana-Farber Cancer Institute and Harvard Medical School, discusses an exploratory analysis from the phase 3 DESTINY-Breast09 trial (NCT04784715) examining the relationship between depth of response and progression-free survival (PFS) in patients with HER2-positive advanced or metastatic breast cancer receiving fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta). Using refined criteria beyond standard RECIST definitions, investigators identified a deep partial response (PR) category for patients achieving 80% to 99% tumor reduction, distinct from "other PR" (≥30% reduction) and stable or progressive disease, to better capture how varying degrees of tumor shrinkage affect therapeutic trajectory. Tolaney noted that these deep responses are not rapid, with a median time to complete response (CR) of 8.4 months (95% CI, 5.6-11.1) and median time to deep PR of 9.6 months (95% CI, 6.8-11.0), and that 80% of the intention-to-treat population did not reach maximal tumor reduction until 24 months of treatment. She concluded that recognizing this extended timeline is a critical advancement for the field, as it underscores that deeper responses are linked with improved PFS even though they may take significant time to manifest.
Efficacy Data for Talquetamab-Based Combos in R/R Myeloma From MonumenTAL-3: Peter Voorhees, MD
Peter Voorhees, MD, of Levine Cancer Institute of Atrium Health and the Wake Forest University School of Medicine, highlights key efficacy data from the phase 3 MonumenTAL-3 trial (NCT05455320) examining talquetamab-tgvs (Talvey) plus daratumumab (Darzalex) with (Tal-DP) or without (Tal-D) pomalidomide (Pomalyst) in patients with relapsed or refractory multiple myeloma, presented at the 2026 EHA Congress. Patients who received Tal-DP (n = 287) experienced a median PFS that was not reached (NR) vs 24.4 months with daratumumab plus pomalidomide and dexamethasone (DPd; n = 290), translating to a 72% reduction in the risk of disease progression or death (HR, 0.28; 95% CI, 0.20-0.40; P < .0001); Tal-D (n = 287) also led to a median PFS that was NR, reflecting a 67% reduction vs DPd (HR, 0.33; 95% CI, 0.24-0.46; P < .0001). Voorhees noted that these statistically significant PFS benefits extended across clinically relevant subgroups, including those who were older, had previous daratumumab exposure, had stage III International Staging System disease, had high-risk cytogenetics, or had soft tissue plasmacytomas. He concluded that both Tal-DP and Tal-D showcase consistent and meaningful efficacy advantages over DPd across this heterogeneous relapsed/refractory population.
Zanubrutinib in Older Patients With Treatment-Naive CLL/SLL: Alessandra Tedeschi MD
Alessandra Tedeschi, MD, of ASST Grande Ospedale Metropolitano Niguarda, discusses results from a subgroup analysis of the phase 3 SEQUOIA trial (NCT03336333) examining zanubrutinib (Brukinsa) in treatment-naive patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who were at least 80 years of age. Data presented at the 2026 EHA Congress showed that at a median follow-up of 78.75 months, the subgroup of patients aged 80 and older treated with zanubrutinib (n = 38) achieved an investigator-assessed PFS estimate of 89.3% (95% CI, 74.0%-95.9%) at 36 months and 63.8% (95% CI, 44.6%-77.8%) at 72 months, with an overall response rate of 100% and a CR rate of 18.4%. Tedeschi noted that treatment discontinuations due to adverse effects (AEs) were infrequent during the first 3 years of therapy, and AE rates adjusted for time on therapy were low and comparable to age-matched populations from the broader trial. She concluded that these data support the use of zanubrutinib in patients 80 years and older, underscoring that advanced age alone should not preclude the use of targeted treatment approaches in CLL.
Development of Biomarkers in RCC: Benjamin Croll, MD
Benjamin Croll, MD, of Fox Chase Cancer Center, discusses the importance of developing effective biomarkers in RCC to predict both prognosis and response to therapy, an objective often described as the field's "holy grail" given the success of genomic markers in guiding therapeutic decisions in other malignancies like prostate cancer. Croll noted that it remains difficult to accurately determine which patients are most likely to benefit from neoadjuvant systemic therapy, as responses vary considerably and there are currently limited tools to distinguish likely responders from nonresponders. This lack of predictive capability poses a clinical challenge, as patients unlikely to benefit may face unnecessary toxicity and surgical delays, and those likely to respond could gain substantial benefit if accurately identified. He concluded that future advances in genomic profiling and biomarker development could allow for a more personalized approach to treatment selection, helping distinguish candidates for systemic therapy from those who should proceed directly to surgery; it could also provide valuable prognostic information.
