Dr George on the Potential Use of Lutetium-177 Earlier in the Treatment Paradigm for mCRPC 

Daniel J. George, MD, medical oncologist, Eleanor Easley Distinguished Professor of Medicine, Duke University School of Medicine, professor of medicine, professor of surgery, Duke Cancer Institute, discusses the emerging potential use of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) and other radioligand therapies earlier in the treatment paradigm and in novel combinations for patients with prostate cancer.

the FDA approved lutetium Lu 177 vipivotide tetraxetan

 for the treatment of adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who have previously received other anticancer therapies, such as androgen receptor pathway inhibitors (ARPIs) and taxane-based chemotherapy. The approval was based on findings from the phase 3 VISION trial (NCT03511664).

George explains that using radioligands such as lutetium Lu 177 vipivotide tetraxetan in earlier disease settings could help improve responses when patients have a lower tumor volume and provide an option for patients who may not be candidates for chemotherapy. Patients in earlier settings could also have less heterogeneous disease, George adds.

In terms of potential combination therapies, research is ongoing to evaluate the potential synergy of lutetium Lu 177 vipivotide tetraxetan with other standard agents, such as hormonal therapy, George continues. For example, the phase 3 PSMAddition trial (NCT04720157) is evaluating the radioligand therapy in combination with standard-of-care ARPIs plus androgen deprivation therapy for patients with metastatic hormone-sensitivie prostate cancer.

, investigated lutetium Lu 177 vipivotide tetraxetan in patients with mCRPC, George notes.

Ongoing studies such as PSMAddition examining the earlier use of lutetium Lu 177 vipivotide tetraxetan, especially in chemotherapy-naive patients, may solidify its role as a key therapeutic option in the management of earlier stages of prostate cancer, George continues. Should this study demonstrate generate positive outcomes, it could support the rationale for using radioligands such as lutetium Lu 177 vipivotide tetraxetan in earlier lines of therapies as a part of different combinations, he concludes.

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Daniel J. George, MD, discusses the potential use of lutetium-177 earlier in the treatment paradigm for metastatic castration-resistant prostate cancer.

Dr George on Other Potential Roles for Radioligand Therapy in Prostate Cancer

Dr George on the CheckMate 8Y8 Trial of Nivolumab With/Without Ipilimumab in Untreated RCC  

Daniel J. George, MD, professor, medicine and surgery, Duke Cancer Institute, discusses key results from the phase 3b CheckMate 8Y8 study (NCT03873402) evaluating nivolumab (Opdivo) plus ipilimumab (Yervoy) vs nivolumab monotherapy in patients with previously untreated advanced renal cell carcinoma (RCC).

The randomized, double-blind study was mandated by the European Medicines Agency (EMA) following the approval of ipilimumab and nivolumab for the first-line treatment of adult patients with intermediate/poor-risk advanced RCC, George begins. Although there is existing data showing activity with nivolumab monotherapy in the refractory setting, there was limited information on its efficacy as a single agent in the phase 3 CheckMate 214 trial (NCT02231749), which supported the regimen's approval. Therefore, the EMA requested comparison data to elucidate the contribution of ipilimumab in this combination therapy, George explains.

The study compares standard-of-care ipilimumab followed by nivolumab with nivolumab monotherapy, focusing on progression-free survival (PFS) and overall survival (OS) as end points, George details. However, immunotherapies administered alone may not always produce significant changes in radiographic PFS (rPFS), despite their potential benefit for patients, he notes. This presents challenges in comparing rPFS between the 2 treatment arms.

Given the nature of immunotherapy response patterns and the size of the study (approximately 430 patients), longer-term outcomes may provide clearer insights into the efficacy of the combination regimen, George continues. The hope is to identify a benefit associated with the ipilimumab-nivolumab combination, with an expectation that ipilimumab adds to the treatment's efficacy, George states.

Recent data presented at the 2023 ASCO Meeting, including the 8-year updated data from CheckMate 214, have shown durable responses with the combination regimen, particularly in patients with intermediate and poor-risk disease, George adds. This underscores the potential benefit of the combination therapy, although further analysis from CheckMate 8Y8 will be crucial in substantiating these findings and understanding any limitations in the trial design that may impact clinical outcomes, George concludes.

Daniel J. George, MD, discusses the phase 3b CheckMate 8Y8 study of nivolumab plus ipilimumab vs nivolumab alone in previously untreated advanced RCC
  

Daniel J. George, MD, professor of medicine and of surgery, Duke Cancer Institute, discusses the clinical benefits of evaluating phenotype in metastatic castration-resistant prostate cancer (mCRPC).

The identification of biomarkers through screening and imaging modalities can provide advantages for mCRPC detection and treatment, George explains. Tumor phenotypes can display mutations or altered gene expression that can be identified through functional imaging techniques, he adds.

These imaging techniques provide information on the uptake of key molecular markers, which can be used to identify distinct tumor subtypes, George explains. The analysis of molecular uptake also provides information on the volume of cancer at different sites of metastases, he notes.

Additionally, PSMA-PET scans can elucidate patterns of disease due to their sensitivity and specificity. Overall, cancer phenotyping can allow for improved and individualized selection of targeted therapies for patients with mCRPC, George concludes.

Daniel J. George, MD, discusses the clinical benefits of evaluating phenotype in metastatic castration-resistant prostate cancer. 
 

Dr. George on the Clinical Benefit of Phenotypic Evaluation in Prostate Cancer  

Daniel J. George, MD, professor of medicine and surgery, and member, Duke Cancer Institute, discusses the expanding role of cabozantinib (Cabometyx) in renal cell carcinoma (RCC).

Cabozantinib is a VEGF inhibitor that was specifically designed to target MET and AXL, in addition to VEGF, says George. 

Clinical validation of the efficacy of cabozantinib in RCC has been observed in multiple clinical trials over the past decade, George explains. Moreover, as cabozantinib selectively inhibits MET and AXL, the agent has demonstrated 

The agent has FDA indications in the frontline and relapsed/refractory settings for patients with RCC, George says.

Additionally, combining cabozantinib with other agents, such as 

, may enhance the utility of the agent in the RCC paradigm, concludes George.

Daniel J. George, MD, discusses the expanding role of cabozantinib in renal cell carcinoma.  



Daniel George, MD

Articles

Dr George on Other Potential Roles for Radioligand Therapy in Prostate Cancer

Dr George on the CheckMate 8Y8 Trial of Nivolumab With/Without Ipilimumab in Untreated RCC

Dr. George on the Clinical Benefit of Phenotypic Evaluation in Prostate Cancer

Dr. George on the Specificity of Cabozantinib in RCC