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Clinical

Benjamin P. Levy, MD; John O. Mascarenhas, MD; Alison J. Moskowitz, MD; Diane Reidy-Lagunes, MD; Tiffany A. Traina, MD, FASCO; David R. Wise, MD, PhD

 41st Annual CFS®: Innovative Cancer Therapy for Tomorrow

Karen M. Winkfield, MD, PhD; Narjust Florez, MD, FASCO; Gilberto de Lima Lopes Junior, MD, MBA, FASCO; Coral Olazagasti, MD; Vonetta M. Williams, MD, PhD

 Fighting Disparities and Saving Lives: An Exploration of Challenges and Solutions in Cancer Care

Jeneth Aquino, DNP, FNP-BC; Beth Sandy, MSN, CRNP, FAPO; Allison M. Walker, ACNP, MSN, MSW, BS

Differentiating Adverse Events for Antibody-Drug Conjugates Across Solid Tumor Management

Adam Weiner, MD, a urologic oncology fellow at the University of California, Los Angeles, discusses his journey toward becoming an oncologist, highlighting his passion for personalized medicine in prostate cancer. He starts by discussing what drew him to the field and explains some of the key experiences he has gained thus far.

Weiner emphasizes the importance of understanding one's passions and motivations. For himself, the latest developments in personalized medicine for prostate cancer, including the use of prostate-specific membrane antigen (PSMA) PET imaging, targeted therapies, and biomarkers like prostate-specific antigen (PSA), are of particular interest.

“My research and clinical focus is on prostate cancer. It is a complex cancer…so you have to help navigate patients and their family members through that initial diagnosis and what can be a very complex evaluation period. Then, you have to help patients figure out what treatment makes the most sense for them by balancing their health priorities and the potential [adverse] effects of treatment,” explains Weiner. “It is a complex process that I find incredibly rewarding.”

Weiner delves deeper into the ongoing research surrounding PSMA positivity and its influence on treatment decisions for patients with prostate cancer. He emphasizes the need for further investigation, particularly in newly diagnosed patients, to fully understand how PSMA expression helps experts decide on what treatments are best.

He also highlights the promise of emerging methods for assessing PSA expression, including correlating PET scan results with RNA and protein levels in tumor tissue. This ongoing research holds the potential to further refine the use of PSMA in personalized medicine.

While there are a number of exciting advancements in prostate cancer treatment, including ongoing clinical trials that combine PSMA with other treatment modalities and the potential of PSMA radioligand therapy as a neoadjuvant treatment prior to surgery, Weiner also underscores the significant unmet needs in precision oncology. Specifically, he shares that there is a need to address the overtreatment and undertreatment of patients, where he highlights the role ongoing research plays in creating individualized care.

This conversation provides valuable insights into the complexities of prostate cancer and the potential of PSMA to revolutionize personalized medicine in this field. Weiner’s passion for research and his commitment to patient care offer a promising outlook for the future of prostate cancer treatment.

Weiner concludes by emphasizing the importance of collaboration within the prostate cancer research community and encourages others to actively engage with the community, share ideas, and contribute to the development of innovative treatment approaches.

“Regardless of any fellows, clinical, or research interests, find that community and become a part of it. Give back to it, and learn what interesting trials or research studies are going on. Expose your research ideas to that community, so that it can be evaluated, criticized, developed, and turned into something that is going to be the most likely to be helpful to your patients.”

Adam Weiner, MD, discusses his journey toward becoming an oncologist with a focus in urology in this episode of Emerging Experts.

Transforming Prostate Cancer Care Through Personalized Medicine

In the latest episode of Emerging Experts, Nazli Dizman, MD, hematology/oncology fellow at MD Anderson Cancer Center, shares the intricacies of her journey towards becoming an oncologist in the US.

Dizman was born and raised in Türkiye. It was here where her training began and where she embarked on her residency training. Following the completion of her residency, she made her way to the US to delve deeper into the realm of cancer research.

“After completing my residency, I came to the United States to do research. I was planning to go back to my home country and do a heme/onc fellowship there, but I really fell in love with cancer research and being able to bring it as early as possible to the patient. So I decided to stay,” Dizman explains in an interview with Targeted Oncology

, reflecting on a pivotal moment that altered the trajectory of her career.

Through her mentors in Türkiye, Dizman was introduced to Sumanta K. Pal, MD, FASCO, medical oncologist and researcher at the City of Hope Comprehensive Cancer Center in California. Since 2016, she has worked under Pal's guidance, immersing herself in the cutting-edge advancements and collaborative atmosphere of cancer research and patient care.

Although a myriad of areas of research captivate Dizman, 1 stands out above the rest: microbiome research.

The gut microbiome impacts one's immune system in many ways, including metabolites going to circulation, stemming circulation, changing immune responses, modulating immune-risk cancers, and more. With limited yet impressive data on this topic, Dizman is a firm believer that understanding of gut microbiome diversities is necessary to discover how they can be associated with better outcomes for patients, particularly for those with renal cell carcinoma.

Dizman’s passion in understanding the immune system and the microbiome as a factor in shaping one's benefit from treatment is something many of her research projects focus on.

“My research right now focuses on understanding the microbiome as a modulator of what comes out, plus, learning technologies to investigate tumor resistant bacteria and ways to modulate them. As a first-year fellow, those are my plans for the next few years,” added Dizman, outlining her goals for the future.

In this episode of Emerging Experts, Nazli Dizman, MD, shares the intricacies of her journey towards becoming an oncologist in the United States. 

Dizman’s Global Pursuit to Cancer Research and Understanding

In season 5, episode 1 of Targeted Talks, Badrinath Konety, MD, president of the Allina Health Cancer Institute and the chief academic officer for Allina Health, delves into the critical topic of prostate cancer screening, particularly for men within a community setting, and discusses some of the recent advancements in the prostate cancer space.

Prostate cancer remains one of the most common cancers among men, leaving many navigating a complex array of decisions regarding screening, treatment, and new advancements. Here, Konety unpacks the latest recommendations, acknowledging the evolving role of the prostate-specific antigen (PSA) test. However, he also acknowledges recognizes its limitations, noting how the use of additional tests may improve accuracy and reduce unnecessary procedures, as well as leveraging MRI.

“PSA still seems to be the bedrock of prostate cancer screening. It's not a great marker, but it is perhaps the best cancer specific marker out there in terms of blood tests,” Konety explains. “MRI is definitely a great adjunct to follow patients who have an elevated PSA and a negative biopsy to better stage the cancer. It's becoming a valuable tool, 1 to guide where to biopsy, but also [to] guide the decision making around whether to biopsy.”

Konety also provides a valuable overview of the treatment landscape, outlining the range of options available for prostate cancer patients. He emphasizes the importance of tailoring treatment based on individual factors, and provides valuable insights into the considerations made when choosing between treatment approaches.

“Now that we're understanding the multidimensionality of cancer and how it can express itself, we're able to better tailor the treatments,” Konety explains.

In addition, the episode explores the impact of minimally invasive and robotic-assisted surgical techniques on both treatment efficacy and accessibility within community settings. Konety discusses the advantages these advancements offer, including potentially improved outcomes, highlighting the possibility for wider access to cutting-edge therapies.

Konety's expertise shines throughout the conversation, offering listeners a comprehensive understanding of the current state of prostate cancer care.

In season 5, episode 1 of Targeted Talks, Badrinath Konety, MD, delves into the critical topic of prostate cancer screening and discusses some of the recent advancements in the prostate cancer space.

A Deep Dive Into the Evolving Landscape of Prostate Cancer

The ECLIPSE trial, a pivotal, phase 3, multi-center, open-label, randomized clinical study, has met its primary end point in metastatic castration-resistant prostate cancer.

177Lu-PSMA-I&T Shows PFS Benefit in mCRPC

The phase 2 CELLVX-230 trial is assessing the potential of FK-PC101 to prevent prostate cancer recurrence and delay additional treatments post-surgery.

Novel immunotherapy FK-PC101 Explored in Prostate Cancer Trial

The FDA has approved the investigational new drug application of AS1986NS for prostate cancer detection and treatment. 

FDA Approves IND for AS1986NS, a New Approach in Prostate Cancer Research

Neal Shore, MD, FACS, discussed a study on survival outcomes in metastatic castration-sensitive prostate cancer comparing apalutamide with abiraterone acetate.

Real-World Survival Outcomes in mCSPC: Comparison of Apalutamide and Abiraterone

In an interview with Targeted Oncology, Neal Shore, MD, FACS, discussed the background, findings, and implications of a real-world study of enzalutamide and apalutamide in patients with metastatic castration-sensitive prostate cancer.

Apalutamide Outperforms Enzalutamide in mCSPC Survival

Mapping ctDNA Shedding Differences in GU Cancers With MRD Testing

Arnab Basu, MD, MPH, FACP, assistant professor in genitourinary medical oncology at the University of Alabama in Birmingham, explains why sensitivity might be higher in urothelial cancer vs other genitourinary (GU) cancers.

Basu has focused his research on using high-sensitivity circulating tumor DNA (ctDNA) assays, specifically minimal residual disease (MRD) tests, in detecting micrometastatic disease across various GU malignancies, including kidney, bladder, and prostate cancers. His research is a mix of retrospective and prospective studies, primarily in urothelial carcinoma but also involving cancers like penile, urethral, and renal cell carcinoma, showing promising results.

In his studies, Basu found that the sensitivity of MRD assays can vary among GU cancers due to biological differences in tumor types. Urothelial carcinoma, for example, is highly aggressive and sheds more DNA into circulation compared with other GU cancers like prostate cancer, which sheds less DNA. This is especially true for prostate cancer in its localized form.

Moreover, Basu’s retrospective studies reveal these shedding differences across tumor types, highlighting ctDNA’s utility and limitations in GU oncology and guiding future research.

MRD assays are currently the best that we have right now in terms of the sensitivity of detecting circulating tumor DNA. However, different diseases have different kinds of biology. A urothelial carcinoma tends to be a lot more aggressive than a favorable-risk renal cell carcinoma. The turnover is high, and there is also, potentially, more shedding of DNA into the circulation.

Certain tumor types tend to shed more than others[due to] squamous differentiation, so squamous tumors shed DNA. Prostate does not shed as much. For localized prostate, there is not a lot of great data, and that is what my fellow colleagues and I put together. We have done a lot of retrospective studies in the clinic showing these kinds of differences.

Videos

Arnab Basu, MD, MPH, FACP, explains why sensitivity might be higher in urothelial cancer vs other genitourinary cancers.

News

Liquid Biopsies Enhance PSMA-Directed Therapies in GU Cancers

Jacob E. Berchuck, MD, assistant professor, Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, discusses the potential of liquid biopsies to enhance clinical decision-making regarding prostate-specific membrane antigen (PSMA)-directed therapies, particularly in light of the FDA-approved Pluvicto (

Lu-PSMA-617) and the development of numerous other PSMA-targeting agents.

With over 30 PSMA-targeting agents in development and the FDA-approved 

Lu-PSMA-617, liquid biopsies offer a promising tool for identifying patients who will benefit from PSMA-directed therapy. Liquid biopsies allow for real-time assessment of the molecular characteristics of a patient’s cancer, which is essential for determining the most effective treatment options.

Lu-PSMA-617 varies significantly, with some responding for up to 2 years while others see no benefit. As a result, Berchuck explains that utilizing clinical biomarkers from liquid biopsies can help tailor treatment decisions and improve patient outcomes in clinical practice.

Overall, the integration of liquid biopsy technology into clinical practice holds great promise for advancing the field of PSMA-directed therapy, allowing for more informed, patient-centered approaches to cancer treatment.

There is an incredible opportunity for liquid biopsies to really inform which patients should and should not receive PSMA-directed therapy in the clinic. I think it is already important, given that we have an FDA-approved drug, [

Lu-PSMA-617] targeting PSMA. But as you mentioned, with the clinical development of many more PSMA-directed therapies, this is only going to become an increasingly important issue in the clinic.

Right now, we have the question: Is this patient going to benefit from [

Lu-PSMA-617]? There is an incredible range in whether patients do or don’t respond. Some patients respond for a year, 18 months, or even 2 years, while other patients do not respond at all. I think using clinical biomarkers, like those we’re developing with this liquid biopsy platform, could really facilitate identifying which patients in the clinic are likely or unlikely to benefit from PSMA-directed therapy.

Jacob E. Berchuck, MD, discusses the potential of liquid biopsies to enhance clinical decision-making regarding PSMA-directed therapies.

AI Tools for Accurate Cancer Diagnosis and Tailored Treatment

Anil Parwani, MD, PhD, professor of pathology at The Ohio State University Wexner Medical Center, discusses how he sees artificial intelligence (AI) technology contributing to personalized medicine and helping to tailor treatment plans for individual patients in the future.


Parwani explains that AI tools are set to propel cancer care forward by providing precise diagnoses and treatment predictions. These will integrate various patient factors to move from personalized to precision medicine.

Just like I mentioned, there are many patients whose prostate cancer looks the same, but they are very different in their outcomes, they are very different in how the cancer progresses. There are other factors in the cancer, the tumor microenvironment, or the patient's demographics, or their background, or their family history. Through building the AI tools, which are predictive and comprehensive, they can pinpoint which patient will benefit from this therapy or not. We think about personalized medicine, but I think about precision. I think that precision diagnosis leads to precision medicine, and AI will help us get to the precise diagnosis, and help us create a bridge from just a diagnosis to a more powerful profile of the patient.

 That is where I think this is headed towards and I can start to see this. When I went to medical school and when I was a resident, I did not even think that we would come to a point where I would be looking at a monitor and looking at signatures of cancer and how they will respond to treatments. My role as a pathologist has evolved completely now because I am not somebody who is just making a diagnosis. I am part of the whole patient care team now and I am part of this process, which will help oncologists get a better and more precise diagnosis for their patients, which will lead to a more precise treatment for them.

Anil Parwani, MD, PhD, discusses how he sees artificial intelligence technology contributing to personalized medicine and helping to tailor treatment plans for individual patients in the future.


Tivozanib Outperforms ICI Combo in Advanced RCC

The TiNivo-2 trial (NCT04987203) investigated the efficacy and safety of combining the PD-1 inhibitor nivolumab (Opdivo) with the selective VEGFR TKI tivozanib (Fotvida) in patients with 

advanced clear-cell renal cell carcinoma 

who had progressed on prior checkpoint inhibitor-based therapy.

Patients were randomized to receive tivozanib plus nivolumab or tivozanib alone. The primary endpoint was progression-free survival (PFS) as assessed by independent radiology review (IRR). The study did not meet its primary endpoint, with a median IRR-assessed PFS of 5.7 months for tivozanib–nivolumab and 7.4 months for tivozanib alone.

Subgroup analyses showed that patients who received checkpoint inhibition as their most recent prior therapy had a longer PFS with tivozanib alone compared to tivozanib–nivolumab. Overall, the results suggest that sequential checkpoint inhibitor therapy may not be beneficial for patients with advanced RCC who have progressed on prior checkpoint inhibitor-based therapy. Tivozanib monotherapy at 1.34 mg daily may be a reasonable option for second-line treatment in this setting.

Here, Toni Choueiri, MD, discusses the rationale behind this drug combination.

If 2α is a transcription factor at the center of all this machinery or degradation of [von Hippel–Lindau (VHL)] at the center of renal cell cancer, and if 2α govern, you know, the activity of multiple gene downstream involved in renal cell cancer carcinogenesis, proliferation, such as VEGF and others. 

So there was a lot of work on targeting it as another mechanism that could be central and more active and more beneficial, and now finally, in terms of anticancer activity. Finally, we're able to have drugs on target that are successful. [For successful], I mean, it's a toxicity-benefit ratio in favor of the responses and activity over toxicity.

Toni Choueiri, MD, discusses the rationale behind the drug combination of tivozanib and nivolumab in the TiNivo-2 study. 



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