OncLive® On Air

In this episode of Oncology Unplugged, host Chandler Park, MD, MSc, FACP, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, was joined by Jame Abraham, MD, FACP, the enterprise chairman of the Department of Hematology and Medical Oncology at Cleveland Clinic and a professor of medicine at the Cleveland Clinic Lerner College of Medicine in Ohio.
Their discussion centered on recent practice-changing advances in breast cancer, spanning treatment de-escalation, antibody-drug conjugates, and the growing role of artificial intelligence (AI) in oncology. Drs Park and Abraham first addressed findings from the phase 3 ASCENT-04 trial (NCT05382286), in which sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) improved progression-free survival over physician’s choice of chemotherapy in the first-line setting in patients with PD-L1–positive metastatic triple-negative breast cancer. Dr Abraham offered guidance on management strategies for neutropenia and diarrhea associated with this combination.
The conversation then turned to treatment de-escalation, highlighting data from the phase 3 OPTIMA trial (ISRCTN42400492), which demonstrated that patients with high-risk, node-positive, hormone receptor–positive early breast cancer and low recurrence scores derived no benefit from adding chemotherapy to endocrine therapy. Dr Abraham underscored the biology-driven rationale for sparing chemotherapy and advocated for ovarian function suppression in high-risk premenopausal patients, citing data from the phase 3 SOFT (NCT00066690) and TEXT (NCT00066703) trials.
Drs Park and Abraham also examined the May 2026 FDA approvals of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for the treatment of patients with early HER2-positive disease, focusing on the results of the phase 3 DESTINY-Breast05 trial (NCT04622319), in which T-DXd reduced the risk of invasive disease or death vs ado-trastuzumab emtansine (Kadcyla). Dr Abraham detailed the importance of interstitial lung (ILD) disease monitoring with T-DXd use and highlighted the reassuring lack of added ILD risk with concurrent radiation that was seen in the trial.
Finally, the experts explored AI’s transformative potential in oncology, emphasizing the importance of clinician involvement in its development, tools like OpenEvidence, and takeaways from the Cleveland Clinic’s AI Summit for Healthcare Professionals, which took place in August 2026. Overall, Drs Park and Abraham affirmed that a patient-centered focus for cancer care should always ultimately guide treatment decisions.

In this episode, produced in coordination with Oncology Nursing News®, Beth Faiman, PhD, MSN, APN-BC, AOCN, FAAN, FAPO, and Sikander Ailawadhi, MD, discussed how on-body subcutaneous administration methods could allow for select at-home administration of therapies for patients with multiple myeloma. Dr Faiman is an adult nurse practitioner in the Department of Hematology/Oncology at the Cleveland Clinic and a clinical member of the Cancer Prevention, Control and Population Research Program at Case Comprehensive Cancer Center in Ohio. Dr Ailawadhi is a consultant in the Division of Hematology/Oncology in the Department of Internal Medicine, a consultant in the Department of Cancer Biology, and a professor of medicine at Mayo Clinic in Rochester, Minnesota.
In the final episode of a 3-part series, Drs Faiman and Ailawadhi explained how they are integrating on-body administration of isatuximab-irfc (Sarclisa Escena) for subcutaneous injection into clinical practice following its July 2026 FDA approval, and the pair also shared how this method could represent a strategy for at-home treatment within the United States in the future.
In the first episode, Drs Faiman and Ailawadhi detailed the transition to subcutaneous administration of anti-CD38 monoclonal antibodies in multiple myeloma management. And in the second episode, they broke down how patient-centric treatment methods are a key focus in myeloma research.

In today’s episode, we spoke with Angeles Alvarez Secord, MD, MHSc. Dr Secord is a professor of obstetrics and gynecology and a member of Duke Cancer Institute in Durham, North Carolina.
In our exclusive interview, Dr Secord discussed the emergence of B7-H4 as an attractive antibody-drug conjugate (ADC) target in gynecologic cancers, noting that expression rates of 80% to 90% or higher across endometrial and ovarian cancers distinguish it favorably from other targets such as folate receptor α and HER2, where high expression thresholds are often required for meaningful benefit. She also highlighted a mechanistic distinction: unlike FRα- or HER2-directed ADCs, which target proteins involved in growth signaling, B7-H4 is more deeply embedded in immune regulation, making it a potentially powerful tool for converting immunologically cold tumors into ones that can respond to checkpoint inhibition.
She reflected on the phase 1 BEHOLD-1 trial (NCT06431594) data presented at the 2026 SGO Annual Meeting on Women’s Cancer, describing the confirmed overall response rate of over 60% in platinum-resistant ovarian cancer as remarkable in a disease where traditional chemotherapy achieves response rates of 15% or less. Dr Secord expressed strong support for the decision to advance this agent into five pivotal phase 3 trials, noting that data of this magnitude clearly justifies further development.
As principal investigator at Duke for the phase 1/2 BEHOLD-2 trial (NCT06796907), Dr Secord walked through the rationale for combining mocertatug rezetecan with dostarlimab-gxly (Jemperli) in endometrial and ovarian cancer. She explained that by suppressing B7-H4’s immunosuppressive effect in the tumor microenvironment, the ADC paradoxically increases immune stimulation and generates neoantigens through cell kill, creating a primed setting for dostarlimab to deliver a synergistic second hit. She also highlighted the BLUESTAR study (NCT05123482) results for puxitatug samrotecan, noting that response rates exceeding 60% in patients previously treated with both platinum and immunotherapy address a critical gap in the current treatment landscape. 
On toxicity management, Dr Secord described a proactive approach to the topoisomerase 1 payload class, emphasizing aggressive antiemetic prophylaxis, liberal use of growth factor support, early intervention for diarrhea with anti-motility agents and dietary modification, and close laboratory monitoring in the first cycles of treatment. She noted that distinguishing between drug-specific toxicities such as stomatitis, interstitial lung disease, and neuropathy across the ADC class is essential for maintaining dose intensity and quality of life.
Finally, Dr Secord addressed the evolving questions of ADC sequencing and B7-H4 biomarker testing. She described herself as a biomarker enthusiast and noted that while current data do not yet show a clear association between B7-H4 expression level and antitumor activity, phase 3 trials represent an important opportunity to conduct robust biomarker collection and assess whether expression magnitude predicts differential benefit. On sequencing, she acknowledged that most phase 3 trials currently exclude patients with prior topoisomerase 1 payload ADC exposure, making clinical trial enrollment essential for generating the cross-ADC sequencing data the field urgently needs.

From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilson Family Chair at the Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.
In this episode, Dr Matulonis was joined by Joyce F. Liu, MD, MPH, a medical oncologist and associate professor of medicine at Harvard Medical School, associate chief and director of clinical research in the Division of Gynecologic Oncology at Dana-Farber Cancer Institute, and associate clinical research officer for the clinical research program at Dana-Farber, all in Boston, Massachusetts. Together, they explored the rapidly expanding landscape of novel therapies for ovarian cancer, spanning the next generation of antibody-drug conjugates (ADCs), resistance mechanisms, cell cycle targets, and emerging strategies for rare histologic subtypes.
Dr Liu opened by surveying the current ADC pipeline in ovarian cancer, noting that while mirvetuximab soravtansine-gynx (Elahere) and fam-trastuzumab deruxtecan-nxki (Enhertu) are already in clinical use, a substantial wave of next-generation agents is now advancing through phase 2 and phase 3 development. She organized these agents by target and payload, highlighting three folate receptor alpha-targeting ADCs with topoisomerase 1 inhibitor payloads: rinatabart sesutecan, sofetabart mipitecan, and torvutatug samrotecan as well as the B7-H4-targeting agent rocertatug rezetecan, CDH6-targeting agents, and Trop-2-directed ADCs including sacituzumab tirumotecan and sacituzumab govitecan-hziy (Trodelvy). Dr Liu noted that early-phase data across several of these agents have shown response rates of 50% or higher, even in heavily pretreated, platinum-resistant populations. Though meaningful, questions remain about response durability as these data continue to mature. A key advantage shared by many of these agents, she emphasized, is the potential for use without high levels of biomarker expression, which could extend eligibility well beyond what current approved ADCs allow.
The conversation then turned to ADC resistance mechanisms and the feasibility of sequential ADC use. Dr Liu described three broad categories of resistance: target-mediated mechanisms, payload-dependent mechanisms, and mechanisms independent of both target and payload. Drawing on evidence from the breast cancer setting, she noted that switching payloads while maintaining the same target can preserve activity, a pattern now emerging in early ovarian cancer data with folate receptor alpha-directed ADCs. Sequential use of two topoisomerase 1 payload ADCs, however, remains a concern, with prospective phase 2 breast cancer trial data suggesting limited activity in that setting. Dr Liu cautioned against drawing direct lines between breast and ovarian cancer biology while acknowledging the question must be actively studied. She and Dr Matulonis also discussed the possibility of ADC rechallenge in patients whose disease progressed in a different treatment context as the settings in which ADCs are introduced continue to evolve.
Dr Liu also addressed dual-payload ADCs, describing them conceptually as analogous to combination chemotherapy, pairing microtubule inhibitor and topoisomerase 1 inhibitor payloads to potentially overcome resistance and improve depth of response. She highlighted a further frontier of novel ADC payloads, including immune-stimulating antibody conjugates, protein degraders, and ATR inhibitors as representing the earliest translational steps from preclinical models into clinical investigation.
Drs Matulonis and Liu then discussed therapeutic strategies for CCNE1-amplified ovarian cancer, a molecularly distinct subset characterized by overexpression of cyclin E1 protein and dependency on the G2/M cell cycle checkpoint. Dr Liu explained that CCNE1 amplification drives constitutive CDK2 activation, forcing cells into premature DNA replication and creating vulnerability to agents that abrogate the compensatory G2/M checkpoint. Two therapeutic approaches have emerged: WEE1 inhibition with azenosertib, which has shown response rates of approximately 30% to 35% in cyclin E1-high platinum-resistant ovarian cancer by immunohistochemistry, compared with 10% to 15% for standard chemotherapy, and CDK2 inhibition and degradation strategies showing similar early signals in CCNE1-amplified tumors. Both approaches are now entering phase 3 evaluation. Dr Liu noted that while CCNE1 amplification is detectable on next-generation sequencing, a validated immunohistochemistry assay for cyclin E1 protein expression is not yet commercially available, though one may emerge as a companion diagnostic if protein-level expression proves to be the more predictive biomarker.
The discussion also covered KIF18A, a kinesin motor protein that stabilizes chromosomes at the metaphase plate during mitosis. In cancers with high chromosomal instability KIF18A activity is critical for cell survival; its inhibition leads to mitotic errors and cell death. Several KIF18A inhibitors are now in active clinical development, with early signals of activity emerging. Dr Liu noted that chromosomal instability alone may not be sufficient to identify optimal candidates for these agents and that additional biomarker refinement will likely be necessary.
Turning to rare histologic subtypes, Dr Liu highlighted two areas of recent progress. In low-grade serous ovarian cancer, the combination of avutometinib, a RAS/RAF clamp that suppresses signaling through the RAS/RAF/MEK pathway, and the FAK inhibitor defactinib (Avmapki Fakzynja Co-pack) received accelerated FDA approval for patients with KRAS-mutated low-grade serous ovarian cancer, supported by phase 2 data demonstrating meaningful activity in this molecularly defined population. A confirmatory international phase 3 trial is ongoing. In clear cell ovarian cancer, emerging phase 2 data for immunotherapy combinations suggest that immunotherapy may hold particular relevance for this subtype, though randomized phase 3 evidence specific to clear cell disease remains limited.
Dr Liu concluded by highlighting two additional areas of interest: BCL-XL inhibition and degradation combinations, which have shown activity in preclinical models and early clinical signals in ovarian cancer; and next-generation immunotherapy approaches, including bispecific antibodies and evolving cellular therapy strategies, which she views as holding genuine potential to generate durable responses in a disease where conventional PD-1/PD-L1 inhibition has had limited reach.

In this episode, produced in coordination with Oncology Nursing News®, Beth Faiman, PhD, MSN, APN-BC, AOCN, FAAN, FAPO, and Sikander Ailawadhi, MD, discussed how on-body subcutaneous administration methods are affecting multiple myeloma management and how these administrations could be a key focus of future health care initiatives. Dr Faiman is an adult nurse practitioner in the Department of Hematology/Oncology at the Cleveland Clinic and a clinical member of the Cancer Prevention, Control and Population Research Program at Case Comprehensive Cancer Center in Ohio. Dr Ailawadhi is a consultant in the Division of Hematology/Oncology in the Department of Internal Medicine, a consultant in the Department of Cancer Biology, and a professor of medicine at Mayo Clinic in Rochester, Minnesota.
In the second episode of a 3-part series, Drs Faiman and Ailawadhi explained how on-body administration of isatuximab-irfc (Sarclisa Escena) for subcutaneous injection is setting the stage for future patient-centric treatment methods, and the pair discussed experiences with this method.
In the first episode, Drs Faiman and Ailawadhi detailed the transition to subcutaneous administration of anti-CD38 monoclonal antibodies in multiple myeloma management.