Five Under 5: Top Oncology Videos for the Week of 11/2

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:

Importance of Novel Second-Line Therapies for HR+ Breast Cancer: Kevin Kalinsky, MD, MS

Kevin Kalinsky, MD, MS, FASCO, of Emory University School of Medicine and Glenn Family Breast Center at Winship Cancer Institute, discussed the need for additional research dedicated to improving post–CDK4/6 inhibitor treatment strategies in patients with advanced hormone receptor–positive breast cancer. He emphasized that additional endocrine-based treatments, along with targeted therapies, could strengthen outcomes following frontline CDK4/6 inhibitor therapy. Kalinsky spotlighted data from the phase 3 postMONARCH study (NCT05169567) of abemaciclib (Verzenio) plus fulvestrant (Faslodex), noting that achieving meaningful second-line benefit beyond six months remains challenging. He added that treatment selection must be individualized, considering factors such as duration of prior therapy and endocrine sensitivity, and that alternative approaches like capecitabine or antibody-drug conjugates may be warranted.

Rationale for Evaluating Pembrolizumab Plus Paclitaxel With/Without Bevacizumab in PROC: Nicoletta Colombo, MD, PhD

Nicoletta Colombo, MD, PhD, of the European Institute of Oncology IRCCS, shed light on the rationale for the phase 3 ENGOT-ov65/KEYNOTE-B96 study (NCT05116189), which examined pembrolizumab (Keytruda) vs placebo in combination with weekly paclitaxel, plus or minus bevacizumab (Avastin), for patients with platinum-resistant, recurrent ovarian cancer. She explained that weekly paclitaxel was selected for its metronomic effects, which can strengthen the tumor immune microenvironment by stimulating dendritic cells, boosting antigen presentation, and decreasing regulatory T cells. Colombo noted that bevacizumab was added in select arms to inhibit VEGF-mediated angiogenesis, normalize tumor vasculature, and encourage T-cell infiltration, further supporting immune activation. She highlighted that previous studies like AGO-OVAR 2.29/ENGOT-ov34 suggested enhanced efficacy of immunotherapy when paired with weekly paclitaxel, supporting the rationale for the trial design of KEYNOTE-B96.

PRO Data With Camizestrant Plus CDK4/6 Inhibition in ESR1+ Breast Cancer: Erica L. Mayer, MD, MPH

Erica L. Mayer, MD, MPH, of Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School, discussed patient-reported outcomes (PROs) from the phase 3 SERENA-6 trial (NCT04964934) examining camizestrant plus a CDK4/6 inhibitor in patients with estrogen receptor–positive, HER2-negative advanced breast cancer following the emergence of an ESR1 mutation. She noted that early switching to camizestrant significantly improved quality of life (QOL) and delays subclinical disease progression compared with an aromatase inhibitor plus a CDK4/6 inhibitor. Mayer highlights that the median time to deterioration in global health status/QOL was 21.0 months for the camizestrant arm versus 6.4 months for the control arm, with similar benefits across pain, physical functioning, emotional functioning, and dyspnea. These findings underscore the meaningful impact of camizestrant on maintaining patient-reported well-being while extending progression-free survival.

Efficacy of Neoadjuvant T-DXd/THP in High-Risk HER2+ Breast Cancer: Paolo Tarantino, MD

Paolo Tarantino, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, spotlighted data from the phase 3 DESTINY-Breast11 trial (NCT05113251) examining fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) combined with a taxane, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP) in patients with high-risk, HER2-positive early breast cancer. He underscored that, for the first time, T-DXd could have a role in the early-stage, curative HER2-positive setting. Findings indicated that neoadjuvant T-DXd/THP elicited a higher pathologic complete response (pCR) rate than dose-dense doxorubicin and cyclophosphamide plus THP, at 67.3% and 56.3%, respectively, with consistent benefit across hormone receptor–positive and –negative subgroups. T-DXd/THP also had fewer grade 3 or serious adverse effects and lower cardiotoxicity, underscoring its potential as a new standard neoadjuvant option for those with moderate- or high-risk HER2-positive disease.

Potential Role of Dato-DXd for Immunotherapy-Ineligible TNBC: Rebecca Dent, MD, MSc, FRCP

Rebecca Dent, MD, MSc, FRCP, of National Cancer Centre Singapore, unpacked data from the phase 3 TROPION-Breast02 trial (NCT05374512) assessing datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) compared with chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer ineligible for immunotherapy. Dent noted that both PD-L1–low (combined positive score [CPS] <10) and PD-L1–high (CPS ≥ 10) subgroups benefited from treatment, suggesting the broad applicability of the TROP-2–targeted antibody-drug conjugate. Most cases of mucositis and ocular toxicities were low grade and manageable with prophylaxis, and the incidence of interstitial lung disease or pneumonitis was rare. She noted that ongoing studies are evaluating Dato-DXd in combination with immune checkpoint inhibition to further enhance efficacy.