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In this episode, CancerNetwork® spoke with breast oncologists Heather McArthur, MD; Erika Hamilton, MD; Hope Rugo, MD; and Paolo Tarantino, MD, PhD, about advances in breast cancer. These developments included recent drug approvals and ongoing research for therapeutic approaches, particularly in the areas of antibody-drug conjugates (ADCs) and CDK4/6 inhibitors, based on presentations they gave at the 25th Annual International Congress on the Future of Breast Cancer (IBC) East in New York City.

Initially, McArthur, Komen Distinguished Chair in Clinical Breast Cancer Research at the Harold C. Simmons Comprehensive Cancer Center, discussed immunotherapy use in high-risk triple-negative and HER2-positive disease, the evolving role of adjuvant CDK4/6 inhibition in HER2-negative breast cancer, and potentially transformative advancements in early breast cancer treatment.

She highlighted the FDA approval for pembrolizumab (Keytruda) in early-stage triple-negative breast cancer, promising clinical trials in estrogen receptor (ER)–positive high-risk early-stage breast cancer, and data from an investigator-initiated trial to treat HER2-positive disease. Additionally, she highlighted an 8.5% improvement in pathological complete response with pembrolizumab added to immunotherapy in the phase 3 KEYNOTE-756 trial (NCT03725059), adding that a further event-free survival benefit may complicate the landscape for CDK4/6 inhibition based on lung and liver toxicities associated with the coadministration of these inhibitors with immunotherapy.

McArthur expressed further excitement for ADC-based combinations for triple-negative disease, as well as in the high-risk residual disease setting. In addition, she highlighted potential advancements in de-escalation strategies and further considerations for ADCs in the HER2-positive and hormone receptor (HR)–positive spaces.

Then, Hamilton, director of Breast Cancer and Gynecologic Cancer Research at the Sarah Cannon Research Institute, highlighted emerging therapies for early breast cancer, as well as her use of datopotamab deruxtecan-dlnk (dato-DXd; Datroway) and fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) given their recent approvals in various breast cancer subtypes. She also touched upon challenges with respect to the implementation of new therapies for early breast cancer into clinical practice.

She initially highlighted new data from the 

2025 American Society of Clinical Oncology (ASCO) Annual Meeting

 Specifically, findings showed that vepdegestrant, an oral proteolysis-targeting chimera (PROTAC), exhibited an efficacy advantage over fulvestrant (Faslodex) in patients with 

-mutant ER-positive, HER2-negative advanced or metastatic disease. Moreover, she highlighted data from the 

 of T-DXd in various combinations for patients with HER2-positive metastatic breast cancer.

Hamilton further highlighted her implementation of T-DXd into clinical practice, citing her use of the agent in patients with metastatic disease, including those with HER2-low and HER2-ultralow breast cancer. She further differentiated dato-DXd from T-DXd, suggesting that they were different classes of drugs due to their different targets: TROP2 vs HER2. She concluded by highlighting an unmet need regarding sustained benefit from endocrine therapy in HR-positive disease, as well as for ADC sequencing and mechanisms of resistance.

Afterward, Rugo, division chief of Breast Medical Oncology, Women’s Cancer Program Director, and professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, discussed efficacy and safety considerations for CDK4/6 inhibitors in early breast cancer treatment. Specifically, she highlighted their high tolerability despite adverse effects and costs associated with their use. Rugo further touched upon a reduction of recurrence rates associated with CDK4/6 inhibition, although longer-term follow-up data were warranted to optimize the duration of therapy and elucidate survival outcomes.

Finally, Tarantino, a research fellow at the Dana-Farber Cancer Institute, concluded by discussing sequencing strategies for ADCs, as well as which breast cancer settings or patient populations will experience the greatest impact with this treatment modality. Tarantino discussed his use of the “sandwich strategy,” where he switches the mechanism of action of treatment after using a TOPO1 ADC. Furthermore, Tarantino highlighted data from the DESTINY-Breast09 and phase 3 ASCENT-04 (NCT06100874) trials, which displayed the enhanced efficacy of 2 ADC combination therapies.

 He concluded by discussing future considerations for combining multiple ADCs.

Cardoso F, O'Shaughnessy J, Liu Z, et al. Pembrolizumab and chemotherapy in high-risk, early-stage, ER+/HER2- breast cancer: a randomized phase 3 trial. 

 2025;31(2):442-448. doi:10.1038/s41591-024-03415-7

Hamilton E, De Laurentiis M, Jhaveri K, et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: results of the global, randomized, phase 3 VERITAC-2 study. 

. 2025;43(suppl 17):LBA1000. doi:10.1200/JCO.2025.43.17_suppl.LBA1000

Tolaney S, Jiang Z, Zhang Q, et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): interim results from DESTINY-Breast09. 

Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. 

. 2025;43(suppl 17):LBA109. doi:10.1200/JCO.2025.43.17_suppl.LBA109

Leading experts in the breast cancer field highlight the use of CDK4/6 inhibitors, antibody-drug conjugates, and other treatment modalities.

Advancements and Evolving Strategies in Breast Cancer Treatment at IBC East

 (Ibtrozi) for patients with locally advanced or metastatic 

-positive non–small cell lung cancer (NSCLC), CancerNetwork

 spoke with Jorge Nieva, MD, about how this regulatory decision may affect the treatment paradigm for this disease.

The approval was supported by findings from the phase 2 TRUST-I trial (NCT04395677) and the phase 2 TRUST-II trial (NCT04919811). The total efficacy population included 157 patients who had no prior treatment with a ROS1 tyrosine kinase inhibitor (TKI) and 113 who were previously treated with a ROS1 TKI.

Top-line results showed an objective response rate (ORR) of 90% (95% CI, 83%-95%) in TRUST-I and 85% (95% CI, 73%-93%) in TRUST-II among patients who had no prior treatment. Of those with pretreated disease, the respective ORRs were 52% (95% CI, 39%-64%) and 62% (95% CI, 46%-75%) in each study population.

According to Nieva, an associate professor of clinical medicine at Keck School of Medicine of the University of Southern California, taletrectinib may offer advantages over other therapies in the 

-positive metastatic NSCLC space based on its improved central nervous system toxicity profile and “excellent” response and progression-free survival data. He stated that taletrectinib would become the go-to first-line agent in his practice. Additionally, he discussed strategies for mitigating toxicities related to taletrectinib, such as nausea and diarrhea, and highlighted the need for additional research to improve immunotherapy options in NSCLC.

“I’m very happy that we have choices for patients, and I’m very happy that we have such a wide variety of drugs, but we still need to do better, and we need to find better ways of using these agents because they’re still not cures for the majority of patients,” Nieva stated. “While these drugs can be helpful at debulking tumors, we still need to do a lot more work on making this a disease of the past for those patients who have it.”

FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. FDA. June 11, 2025. Accessed July 8, 2025. https://tinyurl.com/yc4f379m

According to Jorge Nieva, MD, taletrectinib may be a primary frontline therapy option for those with ROS1-positive non–small cell lung cancer.

Taletrectinib Approval Expands Options in Advanced/Metastatic ROS1+ NSCLC

The medical oncology board examinations are a pivotal time in a clinician's career. However, preparing for and taking this examination comes as a crucial moment when residents/fellows begin their transition to attending.

Although in theory the process of taking an examination and then beginning a new job sounds simple, it is quite complex. The hematology/oncology boards require rigorous preparation. The examination is followed by the new attending position, where clinicians, for the first time, are on their own, making treatment decisions and leading a team.

 as well as those who are just beginning their careers about this time and how they handled studying while experiencing personal and professional changes.

Eric K. Singhi, MD, assistant professor in the Department of General Oncology in the Division of Cancer Medicine and assistant professor in the Department of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, focused on:

His transition from fellow to attending (0:58)

Where students should focus their efforts on studying (2:11)

Advice he would give to those currently studying (2:47)

Nicholas James Hornstein, MD, PhD, assistant professor at Northwell Health Cancer Institute, discussed:

Studying for the boards while balancing a new career (3:18)

Specific study areas the examination focuses on (5:43)

Marc J. Braunstein, MD, associate professor in the Department of Medicine at NYU Grossman Long Island School of Medicine, fellowship program director in hematology/oncology at NYU Langone Health—Long Island, and codirector of the Hematology-Oncology System at NYU Grossman Long Island School of Medicine, highlighted:

How to prepare fellows for the career transition (7:11)

Advice he gives about this transition (8:17)

Nerea M. Lopetegui-Lia, MD, assistant professor in the College of Medicine at The Ohio State University Comprehensive Cancer Center–The James, spoke about:

Best review practices for the examination (9:01)

Advice she would give to those studying (10:15)

MinhTri Nguyen, MD, a medical oncologist with Stanford Medicine, focused on:

As a leadership coach, helping prepare residents/fellows for the career transition (11:36)

Advice he would give to those studying (14:34)

A group of clinicians gives study advice on how to best prepare for the medical oncology board examinations. 

Best Practices for the Medical Oncology Boards

 podcast, co-hosted by Manojkumar Bupathi, MD, MS, executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers, and Benjamin Garmezy, MD, associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, in a recent live session with US Oncology Network and the Pathways Task Force, delved into significant updates that were set to happen at the 2025 American Society of Clinical Oncology (ASCO), focusing on the genitourinary cancer landscape.

Bupathi and Garmezy were joined by John M. Burke, MD, a hematologist and medical oncologist at Rocky Mountain Cancer Centers, and Dhaval R. Shah, MBBS, a medical oncologist from Christiana Care.

A primary focus of the discussion was the phase 3 KEYNOTE-564 trial (NCT03142334), a pivotal trial for patients with renal cell carcinoma (RCC). This study investigated pembrolizumab (Keytruda) as adjuvant therapy for patients with clear cell RCC who had undergone surgical resection and presented with intermediate-high or high-risk features.

Garmezy highlighted the "clear separation of the curves" in disease-free survival (DFS), with an HR of 0.68, and a compelling 5% difference in long-term overall survival, signifying a benefit for "about 1 in 20 patients". Despite about 20% of patients discontinuing treatment due to toxicity, the overall safety profile of pembrolizumab was considered well-tolerated, with no statistically significant difference in quality of life compared with placebo.

Burke provided the panel with his perspective on evaluating such trials. He emphasized the importance of scrutinizing study design flaws, even in "randomized, double-blind, placebo-controlled, phase 3 clinical trials," which are often seen as the "epitome of great science". Key questions for consideration include the appropriateness of the control arm (placebo in KEYNOTE-564 was deemed appropriate), the validity of surrogate end points like DFS, and the presence of "informative censoring"—a form of bias that can skew results. Burke noted that informative censoring can occur if patients drop out of a trial due to disappointment with their randomized arm or due to drug toxicity, which can make the treatment arm's progression-free survival look better than it truly is.

The discussion also touched upon the consistency of KEYNOTE-564’s findings with other trials. Garmezy noted that while pembrolizumab showed positive results, other adjuvant studies involving atezolizumab (Tecentriq), nivolumab (Opdivo), and nivolumab plus ipilimumab (Yervoy) had no significant difference, potentially due to differences in drug type or duration of therapy (6 vs 12 months). Shah affirmed that despite these nuances, the overall survival benefit seen in KEYNOTE-564 justifies the use of adjuvant pembrolizumab for eligible patients, emphasizing adherence to the exact trial criteria.

Beyond kidney cancer, the podcast previewed discussions on the phase 3 NIAGARA trial (NCT03732677) for perioperative bladder cancer and the phase 3 TALAPRO-2 trial (NCT03395197) for first-line metastatic castrate-resistant prostate cancer (mCRPC). Bupathi highlighted the ongoing debate within the Pathways Committees regarding the integration of new data vs established practices, particularly concerning the timeline for new drugs to be incorporated into pathways. Burke clarified that while Pathways guides value-driven decisions, physicians retain the autonomy to prescribe off-pathway regimens, though financial implications might arise. The episode concluded with a look ahead to more data releases, underscoring the dynamic nature of oncology practice and the continuous evaluation of therapies for optimal patient care.

Choueiri TK, Tomczak P, Park SH, et al; KEYNOTE-564 Investigators. Overall survival with adjuvant pembrolizumab in renal-cell carcinoma. N Engl J Med. 2024;390(15):1359-1371. doi:10.1056/NEJMoa2312695

Dive into the latest in genitourinary oncology with "Oncology Decoded," featuring discussions on KEYNOTE-564 with RCC.

Unveiling Advances in GU Cancers: Insights from Oncology Decoded

, Benjamin Golas, MD, spoke about the current treatment landscape for patients with peritoneal carcinomatosis, discussing how the use of pressurized intraperitoneal aerosolized chemotherapy (PIPAC) may offer improvements in clinical outcomes.

Golas is the chief of Surgical Oncology of the Central Region for Hackensack Meridian Health.

According to Golas, standard therapeutic approaches include combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), which may cause collateral damage to healthy tissue while eliciting toxicities such as nausea, vomiting, and bone marrow suppression. Additionally, certain surgical procedures may last up to 14 hours and confer an extensive morbidity profile, thereby increasing complication rates.

Golas described how PIPAC, a minimally invasive laparoscopic technique, may help avoid pain and other adverse effects associated with surgery while facilitating more direct delivery of chemotherapy in the peritoneal cavity. He noted that treatment with PIPAC typically takes 45 minutes to an hour, allowing some patients to return home on the same day of the procedure.

Although clinicians are still learning the correct indications for PIPAC, Golas stated that any patient with peritoneal carcinomatosis should be a candidate to receive treatment with this strategy. Furthermore, he described how the next steps for improving outcomes in this population include finding new ways to incorporate PIPAC into more extensive treatment plans for patients.

“PIPAC is a new treatment and a new potential option that doesn't replace systemic chemotherapy, but I do think it can work in conjunction with systemic chemotherapy. We can offer this bimodal approach where we're directly treating the peritoneal disease and offering [intravenous] chemotherapy,” Golas stated. “We clearly have a long way to go in terms of clinical trials and learning what the best ways are to use this. But there are patients out there who will benefit from that, so I think referral to a center that focuses and has expertise in PIPAC for patients with peritoneal carcinomatosis is critical.”

Benjamin Golas, MD, discusses how the use of PIPAC may work in conjunction with systemic chemotherapy for those with peritoneal carcinomatosis.

Harnessing PIPAC to Improve Outcomes in Peritoneal Carcinomatosis

, CancerNetwork® put together an X Spaces discussion hosted by Stephen Liu, MD; and Joshua Sabari, MD, to highlight the most intriguing and practice-changing lung cancer abstracts. Discussed topics ranged from long-term follow-up with commonplace therapies to an analysis of what time of day is best to administer immunochemotherapy.

Liu, an associate professor of medicine at Georgetown University and the director of thoracic oncology and head of developmental therapeutics at the Georgetown Lombardi Comprehensive Cancer Center, and Sabari, an assistant professor in the Department of Medicine at the New York University Grossman School of Medicine and the director of high reliability organization initiatives at the Perlmutter Cancer Center, shared expert insights on the latest non–small cell lung cancer (NSCLC) and SCLC breakthroughs.

Trials of note that they discussed included:

The phase 3 DeLLphi-304 trial (NCT05740566)

: "Tarlatamab (Imdelltra) vs Chemotherapy (CTx) as Second-Line (2L) Treatment for Small Cell Lung Cancer (SCLC): Primary Analysis of Ph3 DeLLphi-304"

: "Lurbinectedin (Lurbi) + Atezolizumab (Atezo) as First-Line (1L) Maintenance Treatment (tx) in Patients (pts) With Extensive-Stage Small Cell Lung Cancer (ES-SCLC): Primary Results of the Phase 3 IMforte Trial"

The phase 3 CheckMate 816 trial (NCT02998528)

: "Overall Survival With Neoadjuvant Nivolumab (NIVO) + Chemotherapy (Chemo) in Patients With Resectable NSCLC in CheckMate 816"

The phase 3 PACIFIC15 trial (NCT05549037): "Randomized Trial of Relevance of Time-of-Day of Immunochemotherapy for Progression-Free and Overall Survival in Patients With Non–Small Cell Lung Cancer"

The phase 3 Beamion LUNG-1 trial (NCT04886804): "Patient-Reported Outcomes (PRO) Evaluating Physical Functioning and Symptoms in Patients With Pretreated HER2-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC): Results From the Beamion LUNG-1 trial"

The phase 3 ARTEMIA trial (NCT06472245): "Phase 3 Trial of the Therapeutic Cancer Vaccine OSE2101 Versus Docetaxel in Patients With Metastatic Non-Small Cell Lung Cancer and Secondary Resistance to Immunotherapy"

Rudin C, Mountzios G, Sun L, et al. Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): primary analysis of ph3 DeLLphi-304. 

. 2025;43(suppl 17):LBA8008. doi:10.1200/JCO.2025.43.17_suppl.LBA8008

Paz-Ares L, Borghaei H, Liu SV, et al. Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): primary results of the phase 3 IMforte trial. 

2025;43(suppl 16):8006. doi:10.1200/JCO.2025.43.16_suppl.8006

Forde PM, Spicer JD, Provencio M, et al. Overall survival with neoadjuvant nivolumab + chemotherapy in patients with resectable NSCLC in CheckMate 816. 

. 2025;43(suppl 17):LBA8000. doi:10.1200/JCO.2025.43.17_suppl.LBA8000

Zhang Y, Huang Z, Zeng L, et al. Randomized trial of relevance of time-of-day of immunochemotherapy for progression-free and overall survival in patients with non-small cell lung cancer. 

. 2025;43(suppl 16):8516. doi:10.1200/JCO.2025.43.16_suppl.8516

Sabari JK, Nadal E, Hendriks L, et al. Patient-reported outcomes (PRO) evaluating physical functioning and symptoms in patients with pretreated HER2-mutant advanced non-small cell lung cancer (NSCLC): results from the Beamion LUNG-1 trial. 

2025;43(suppl 16):8620. doi:10.1200/JCO.2025.43.16_suppl.8620

Liu SV, Guibert C, Tostivint EP, et al. Phase 3 trial of the therapeutic cancer vaccine OSE2101 versus docetaxel in patients with metastatic non-small cell lung cancer and secondary resistance to immunotherapy. 

. 2025;43(suppl 16):TPS8651. doi:10.1200/JCO.2025.43.16_suppl.TPS8651

Stephen Liu, MD; and Joshua Sabari, MD, discuss the most intriguing non–small cell lung cancer and small cell lung cancer breakthroughs from the meeting. 

Practice-Changing Lung Cancer Data From the 2025 ASCO Annual Meeting

discussion, Manojkumar Bupathi, MD, MS, met with Benjamin Garmezy, MD, after the 

 to review data from the late-breaking abstracts, poster sessions, and other presentations of interest that may shift the paradigm across different genitourinary malignancies.

Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners, also specializing in genitourinary cancers.

These experts highlighted their top abstracts and presentations from this year’s ASCO Annual Meeting, breaking down the results and clinical implications of key research in prostate cancer, bladder cancer, and other patient populations. Noteworthy studies and analyses included the following:

Niraparib (Zejula) plus abiraterone acetate (Zytiga) with prednisone (AAP) reached the primary end point of radiographic progression-free survival (rPFS), reducing the risk of radiographic progression or death by 48% (HR, 0.52; 95% CI, 0.37-0.72; 

Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, discuss abstracts from the 2025 ASCO Annual Meeting that may impact genitourinary cancer care.

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