Drs Antonarakis and Jha on Extending Clinical Trials to the Community Setting

Emmanuel Antonarakis, MD, associate director, Translational Research, Masonic Cancer Center, University of Minnesota, Clark Endowed Professor of Medicine, University of Minnesota Medical School; and Gautam Jha, MD, medical director, M Health Fairview Masonic Cancer Clinic and the Advanced Treatment Center at the M Health Fairview Clinics and Surgery Center—Minneapolis, chair, cancer committee, M Health Fairview Ridges Hospital, highlight the significance of collaboration to extend the reach of clinical trials beyond the confines of university hospitals, thus enhancing patient accessibility and engagement within the community setting.

In particular, Antonarakis and Jha discussed the collaborative effort used by the University of Minnesota and surrounding community cancer centers to drive enrollment to the phase 3 ECLIPSE trial (NCT05204927), which evaluated 177Lu-PSMA-I&T vs standard-of-care hormone therapy with abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in patients with metastatic castration-resistant prostate cancer (mCRPC) who experienced progressive disease and received prior treatment with an androgen receptor–directed therapy.

By partnering with community oncologists affiliated with the University of Minnesota, the goal was to broaden the trial’s patient pool. Although 177Lu-PSMA-I&T, which is a radiopharmaceutical, required administration at the University of Minnesota due to safety protocols, patient identification and recruitment efforts were decentralized to community settings, Antonarakis says.

Jha underscores the practical benefits of this collaborative approach, particularly in alleviating the burden of travel for patients—a factor often impeding trial participation for those being treated in the community. Leveraging existing networks within the community, Jha explains that he and his team effectively engaged local oncologists to identify potential candidates for the trial.

Jha's commitment to supporting his colleagues in identifying eligible patients underscores the collaborative ethos driving this endeavor. This collaborative model demonstrates a pragmatic approach to trial recruitment, capitalizing on the strengths of both academic and community oncology settings.

By decentralizing patient identification and engagement efforts, the trial effectively satisfied its reach and potential impact on advancing prostate cancer research and treatment options for patients near and around the University of Minnesota, they conclude.

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Emmanuel Antonarakis, MD, and Gautam Jha, MD, on collaboration efforts extending the reach of clinical trials beyond university hospitals.

Dr Antonarakis on Community Enrollment in the ECLIPSE Trial in Prostate Cancer

Emmanuel Antonarakis, MD, associate director, Translational Research, Masonic Cancer Center, University of Minnesota, Clark Endowed Professor of Medicine, University of Minnesota Medical School, provides insights into the phase 3 ECLIPSE trial (NCT05204927), detailing how collaboration with community oncologists spurred increased awareness and enrollment for eligible patients with prostate cancer.

The study evaluated 177Lu-PSMA-I&T vs standard-of-care hormone therapy (abiraterone acetate [Zytiga] or enzalutamide [Xtandi]) in patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressive disease and received prior treatment with an androgen receptor (AR)–directed therapy. The trial enrolled 439 patients with mCRPC and documented positive prostate-specific membrane antigen PET imaging. The M Health Fairview Ridges Cancer Clinic in Burnsville, Minnesota, in partnership with the Masonic Cancer Center, University of Minnesota, was 1 of the study sites, and patients treated during this study were also enrolled from nearby community cancer centers.

Antonarakis says that the trial targeted patients who had progressed on at least 1 novel AR-targeted therapy but had not undergone chemotherapy. Since this subset of patients was chemotherapy naive, it presented an opportunity to explore the potential benefits of administering radioligand therapy earlier in the treatment continuum. Drawing parallels to the FDA-approved lutetium Lu 177 vipivotide tetraxetan (Pluvicto; formerly 177Lu-PSMA-617), which mandates prior failure of both novel hormone therapy and taxane-based chemotherapy for eligibility, Antonarakis highlights the ECLIPSE trial's objective of expanding treatment options to patients at an earlier stage to potentially enhance clinical outcomes.

The rationale behind the ECLIPSE trial lies in addressing these challenges by offering radioligand therapy to patients who have failed hormone therapy but have not yet undergone chemotherapy. Antonarakis highlights the significance of extending this treatment option to patients earlier in their disease course, particularly those who are fitter and prefer to avoid chemotherapy-related toxicities. Notably, ECLIPSE represents a pioneering effort in the region, marking the first instance where radioligand therapy is available to patients in Minnesota and nearby states without the prerequisite of prior chemotherapy.

Antonarakis underscores the importance of the study for exploring the feasibility and efficacy of administering radioligand therapy earlier in the treatment paradigm for patients with mCRPC with the ultimate goal of expanding access to this innovative treatment modality to a wider patient population.

Emmanuel Antonarakis, MD, discusses community enrollment in the ECLIPSE trial in prostate cancer.

Drs Jha and Antonarakis on Collaboration Between Community and Academic Oncologists

Gautam Jha, MD, medical director, M Health Fairview Masonic Cancer Clinic and the Advanced Treatment Center at the M Health Fairview Clinics and Surgery Center—Minneapolis, chair, cancer committee, M Health Fairview Ridges Hospital; and Emmanuel Antonarakis, MD, associate director, Translational Research, Masonic Cancer Center, University of Minnesota, Clark Endowed Professor of Medicine, University of Minnesota Medical School, discuss the practicality and advantages of collaborative efforts between community and academic oncologists.

By addressing logistical challenges and dispelling historical misconceptions, both physicians hope that the broader oncology community can work toward a more inclusive and collaborative approach to cancer research and patient care. The physicians outline several hurdles faced by community practitioners, noting potential limitations in awareness of all currently available clinical trials, as well as the broad spectrum of patients with cancer they treat in practice. Unlike university oncologists who specialize in specific cancer types, community oncologists must stay abreast of developments across various spaces, posing a significant challenge in remaining fully informed on clinical trial options and recommendations across all disease states.

Highlighting historical misconceptions surrounding the relationship between academic and community oncologists, Antonarakis emphasizes the evolving dynamic characterized by mutual respect and collaboration rather than rivalry. He also explains that community oncologists should perceive academic colleagues as valuable resources for discussing complex cases, rather than only referring patients to academic centers for clinical trials. He stresses the ethical imperative of returning patients to their community physicians if they do not meet trial eligibility criteria, emphasizing the need to avoid any perception of patient poaching.

Both physicians mention the imperative nature of maintaining patient-centered care and fostering collaboration to enhance clinical trial enrollment. Jha highlights the logistical challenges faced by community oncologists, underscoring the need for increased support and resources to facilitate trial participation. He notes the importance of addressing time constraints and adds that adequate training and support is required to enable community oncologists to effectively overcome these barriers.

Antonarakis discusses the importance of dispelling misconceptions and fostering a collaborative spirit between academic and community oncologists. He says clinicians have an ethical obligation to prioritize patient care and maintain strong relationships with referring physicians. By ensuring open communication and mutual respect, Antonarakis suggests that the oncology community could work toward overcoming existing barriers to trial enrollment and fostering a more inclusive and collaborative approach to cancer research and care.

Gautam Jha, MD, and Emmanuel Antonarakis, MD, on the advantages of collaborative efforts between community and academic oncologists.

Dr Antonarakis on Early Intervention With PARP Inhibitors in mHSPC 

Emmanuel Antonarakis, MD, associate director, Translational Research, Masonic Cancer Center, the Clark Endowed Professor of Medicine, University of Minnesota Medical School, discusses current clinical trials investigating the use of PARP inhibitors that may push the boundaries of the treatment paradigm for metastatic prostate cancer, including studies shifting treatments toward earlier stages of the disease, specifically targeting the hormone-sensitive phase.

Antonarakis highlights clinical trials such as the phase 3 AMPLITUDE (NCT04497844), TALAPRO-3 (NCT04821622), and EvoPAR-PR01 (NCT06120491) trials, which are investigating the efficacy of PARP inhibitors combined with androgen deprivation therapy (ADT) in this setting.

AMPLITUDE explored the use of niraparib (Zejula) in combination with abiraterone acetate (Zytiga) and prednisone vs abiraterone plus prednisone and placebo in patients with newly diagnosed, metastatic hormone-sensitive prostate cancer (mHSPC) deleterious germline or somatic harboring homologous recombination repair (HRR) gene mutations. This trial aims to determine whether initiating PARP inhibition at this early stage, rather than waiting until castration resistance develops, improves outcomes, Antonarakis explains.

TALAPRO-3 is comparing the combination talazoparib (Talzenna) plus enzalutamide (Xtandi) and ADT versus Enzalutamide plus placebo in patients with mHSPC with DNA damage response (DDR) alterations. Previously, in June 2023, 

the FDA approved talazoparib plus enzalutamide

 for use in patients with HRR gene–mutated metastatic castration-resistant prostate cancer (mCRPC), based on data from the phase 3 TALAPRO-2 trial (NCT03395197). TALAPRO-3 is aiming to ascertain the benefit of adding a PARP inhibitor in the first-line treatment regimen for patients with mHSPC, Antonarakis notes.

EvoPAR-PR01, which is still recruiting patients, is evaluating saruparib (AZD5305) in combination with physician’s choice of hormonal therapy—abiraterone acetate, enzalutamide, or darolutamide (Nubeqa)—vs physician’s choice of hormonal therapy plus placebo in patients with mHSPC. The study will include two cohorts of patients: those with and without HRR gene mutations.

These trials address the question of whether incorporating PARP inhibitors earlier in the treatment paradigm for mHSPC, particularly in patients with specific biomarkers such as HRR gene mutations or 

mutations, offers superior outcomes compared to delaying PARP inhibition until castration resistance occurs, Antonarakis explains.

By targeting the hormone-sensitive phase of metastatic prostate cancer, these trials aim to optimize treatment strategies and potentially delay disease progression. The results of these studies will provide valuable insights into the role of PARP inhibitors in combination with standard therapies in the management of metastatic prostate cancer and may influence future treatment guidelines, he concludes.

Emmanuel Antonarakis, MD, discusses the significance of TALPRO-3, EVOPAR, and AMPLITUDE trials on the metastatic prostate cancer treatment paradigm. 

Emmanuel Antonarakis, MD, associate director for Translational Research, Clark Endowed Professor of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School Masonic Cancer Center, discusses the benefits of somatic and germline testing for patients with prostate cancer. 

Oncological and neurological guidelines recommend germline testing for patients with high-risk localized prostate cancer or positive pelvic lymph node disease, Antonarakis states. Conversely, patients with low-risk localized prostate cancer are not typically directed to undergo germline testing, with the exception of individuals with a family history of prostate cancer or a genetic background that may increase the risk of displaying a germline mutation.

Unlike germline testing, somatic testing is not generally recommended for this patient population, as there is currently no somatic-based treatment approach for patients in this setting, Antonarakis continues.

Finally, patients with metastatic prostate cancer are recommended to undergo germline and somatic genetic testing. The genetic information obtained could help clinicians choose an appropriate targeted gene therapy and provide counsel to patients with a hereditary risk of prostate and other cancers, Antonarakis concludes.

Emmanuel Antonarakis, MD, discusses the benefits of somatic and germline testing for patients with prostate cancer. 

Dr. Antonarakis on the Benefits of Genetic Testing for Select Patients With Prostate Cancer

Emmanuel Antonarakis, MD, associate director for Translational Research, Clark Endowed Professor of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School Masonic Cancer Center, discusses the different therapeutic agents that are available for patients with metastatic castration-resistant prostate cancer (mCRPC) who display either somatic or germline mutations. 

In this patient population, Antonarakis explained 2 classes of therapeutic agents utilized in prostate cancer: PARP inhibitors and PD-1 inhibitors.

The PARP inhibitors olaparib (Lynparza) and rucaparib (Rubraca) have been approved for patients with mCRPC. Olaparib has been approved for tumors with deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated. Rucaparib is indicated for patients with germline or somatic 

mutations, somewhat limiting its use in this patient population, Antonarakis notes.

Conversely, pembrolizumab (Keytruda) is indicated for use in patients with prostate cancer who display mismatch repair deficiency/microsatellite instability. These patients have highly immunogenic tumors, which in turn make them responsive to immune checkpoint inhibitors. Accordingly, pembrolizumab is an effective option for this patient population, Antonarakis concludes. 

Emmanuel Antonarakis, MD, discusses the different therapeutic agents that are available for patients with metastatic castration-resistant prostate cancer who display either somatic or germline mutations. 

Dr. Antonarakis on Therapeutic Agents for Select Patients With mCRPC

Emmanuel S. Antonarakis, MD, associate professor of oncology, Johns Hopkins University, discusses the clinical implications of an MMR deficiency in patients with prostate cancer.

MMR genes are responsible for Lynch syndrome if inherited, says Antonarakis, but they can also be acquired. These genes include 

. These are the genes that cause hypermutated tumors with hundreds, if not thousands, of mutations. Therapeutically, this is important because in solid tumors, if a patient harbors a MMR deficiency or mutation, they can receive pembrolizumab (Keytruda), a PD-1 inhibitor, which is now FDA approved for solid tumors agnostic of origin as long as the patient has the MMR gene mutation, explains Antonarakis.

Unfortunately, this only represents about 3% to 5% of all advanced prostate cancers, says Antonarakis. Nonetheless, pembrolizumab can be used in this patient population and is included in the guidelines for prostate cancer.

Emmanuel S. Antonarakis, MD

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