Five Under 5: Top Oncology Videos for the Week of 5/18

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:

Potential Relevance of the DESTINY-Breast09 Trial in HER2+ Breast Cancer: Paolo Tarantino, MD

Paolo Tarantino, MD, PhD, of Dana-Farber Cancer Institute, discusses key breast cancer research to be presented at the 2025 ASCO Annual Meeting. He highlights the phase 3 DESTINY-Breast09 trial (NCT04784715), which evaluates fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta) as a potential chemotherapy-sparing first-line treatment for HER2-positive metastatic breast cancer. Tarantino also notes the ASCENT-04 trial (EudraCT 2021-005743-79), where sacituzumab govitecan-hziy (Trodelvy) combined with pembrolizumab (Keytruda) shows promise in PD-L1–positive metastatic triple-negative breast cancer (TNBC). Additionally, the phase 2 NEOSTAR study (NCT03158129) is investigating sacituzumab govitecan with pembrolizumab in early-stage TNBC. Overall, he emphasizes a growing trend toward earlier use of antibody-drug conjugates to improve patient outcomes.

Preliminary Efficacy of MZB1 TCR-Like CAR T-Cell Therapy in Myeloma: Elena Maroto-Martin, PhD

Elena Maroto-Martin, PhD, of Dana-Farber Cancer Institute, discusses early efficacy data on an MZB1-targeted T-cell receptor (TCR)–like CAR T-cell therapy in preclinical models of multiple myeloma and Waldenström macroglobulinemia. The therapy demonstrated strong tumor cell killing and specificity against MZB1/HLA-A2–positive cells, including primary patient samples. It also showed HLA cross-reactivity, targeting MZB1 presented by other HLA alleles such as HLA-A24/A23. In vivo, the treatment eradicated tumor cells and prolonged overall survival in a humanized multiple myeloma model. These findings support further development of TCR-like CAR T therapies targeting intracellular antigens in multiple myeloma and other B-cell malignancies.

Responses With RAS(ON) Inhibition in Preclinical Pancreatic Cancer Models: Robert Herman Vonderheide, MD, DPhil

Robert Herman Vonderheide, MD, DPhil, of Penn Medicine, discusses preclinical data demonstrating that KRAS(ON) multi-selective inhibitors produce significant tumor regression in pancreatic ductal adenocarcinoma models. The antitumor effect was notably reduced in animals lacking T cells, indicating that the adaptive immune system plays a crucial role in the therapeutic response. Adding immune therapies, such as checkpoint inhibitors, further deepened tumor regressions and, in some cases, led to sustained remissions. These findings support combining RAS(ON) inhibitors like RMC-6236 with immunotherapy in clinical trials, including the ongoing phase 1/1b study (NCT05379985) for patients with KRAS G12-mutant solid tumors.

Safety of Earlier Use of Lu 177 Vipivotide Tetraxetan PSMA+ mCRPC: Jorge A. Garcia, MD

Jorge A. Garcia, MD, of University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center, discusses the safety of using lutetium Lu 177 vipivotide tetraxetan (Pluvicto) earlier in the treatment of prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer (mCRPC). The FDA expanded its indication based on the phase 3 PSMAfore trial (NCT04689828), which showed improved radiographic progression-free survival vs a change in androgen receptor pathway inhibitor therapy. Garcia notes that the safety profile in this earlier, chemotherapy-naive setting remains favorable, with common adverse effects (AEs) including fatigue and anemia, mostly of low grade. Grade 3 or higher AEs were uncommon, and discontinuation due to toxicity was low, supporting the tolerability of earlier use of this radioligand therapy.

Ongoing Therapeutic Challenges in Soft Tissue Sarcomas: Erica Maria Pimenta, MD, PhD

Erica Maria Pimenta, MD, of Dana-Farber Cancer Institute and Brigham and Women’s Hospital, discusses the ongoing challenges and unmet needs in treating soft tissue sarcomas, particularly dedifferentiated liposarcoma (DDLPS). She highlights that current treatment relies heavily on empiric chemotherapy, which offers limited benefit and significant toxicity, underscoring the need for targeted therapies. Pimenta explains that research is focusing on understanding the molecular and epigenetic drivers of DDLPS to identify new biomarkers and therapeutic targets. Despite previous modest results with immune checkpoint inhibitors and targeted agents, she is optimistic that deeper insights into tumor heterogeneity and the tumor microenvironment will improve future trial design and patient outcomes.