Chandler Park, MD, MSc, FACP, co-director, Genitourinary Clinical Trials, Norton Cancer Institute, discusses the navigation and selection of later-line treatments for patients with metastatic urothelial carcinoma.

The number of available therapeutic options in bladder cancer has significantly expanded in recent years, Park begins. There is also a substantial amount of new data on the use of molecular testing and circulating tumor DNA for patients with stage II disease, he adds. However, precision medicine approaches are needed to navigate later-line treatment decisions for patients in the metastatic setting who have progressed on platinum-doublet chemotherapy in combination with avelumab (Bavencio), Park says. 

Tools like next-generation sequencing could be used to identify patients whose tumors harbor 

 alterations, Park explains. These patients may benefit from a targeted therapy such as erdafitinib (Balversa). 

Conversely, the antibody-drug conjugate (ADC) enfortumab vedotin-ejfv (Padcev) is an effective option for patients who do not harbor these mutations, Park continues. In April 2023, 

this agent was granted accelerated approval in combination with pembrolizumab (Keytruda)

 for patients with locally advanced or metastatic urothelial carcinoma who are cisplatin-ineligible based on data from cohort A and cohort K of the phase 1/2 EV-103/KEYNOTE-869 study (NCT03288545). 

 in the United States for patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

Additionally, other ADCs like sacituzumab govitecan-hziy (Trodelvy) my serve as an effective alternative to enfortumab vedotin for patients who have aggressive peripheral neuropathy, according to Park. This adverse effect is commonly observed in those receiving cisplatin and gemcitabine-based regimens, and is also seen in almost half of patients treated with enfortumab vedotin, Park adds. Accordingly, enfortumab vedotin is not an option for this population, he concludes.

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Chandler Park, MD, MSc, FACP, discusses the navigation and selection of later-line treatments for patients with metastatic urothelial carcinoma.
 


Dr Park on Navigating of Later-line Treatment Options in Metastatic Urothelial Carcinoma

Chandler Park, MD, MSc, FACP, co-director, Genitourinary Clinical Trials at Norton Cancer Institute in Louisville, Kentucky discusses how the emerging field of radiotheranostics and increasing utilization of biomarker testing will improve the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Now that the efficacy of PARP inhibitors in 

-mutated metastatic castration-resistant prostate cancer (mCRPC) has been well established, current efforts aim to utilize these therapies in mHSPC, according to Park. Research in this space has demonstrated the heterogeneity of metastatic prostate adenocarcinomas, and the subsequent influence of germline and somatic mutations on treatment benefit and selection, Park explains.

Accordingly, all of these patients can benefit from somatic and germline genetic testing. Individuals with certain mutations should then be considered for clinical trials in the mHSPC space, Park adds. The presence of common mutations like 

 have become indicative of efficacy with current therapeutics; however, novel mutations such as 

 are increasingly included in biomarker screening, Park says.

The utilization of radiopharmaceuticals and molecular imaging is also increasing in prostate cancer, Park adds. The phase 3 VISION study (NCT03511664) contributed to this advancement by demonstrating the efficacy of the radioligand Lutetium 177 (

Lu-PSMA-617) as a third-line treatment for patients who progressed to mCRPC on a taxane and aromatase receptor (AR) inhibitor, Park says.

In December 2022, a press release also reported that the phase 3 PSMAfore trial (NCT04689828) of 

Lu-PSMA-617 met its primary end point of progression-free survival, Park adds. The trial was conducted in patients with mHSPC who had been previously treated with alternate AR-directed therapy before exposure to a taxane-containing regimen. Initial data from this trial will be released in 2023, he notes.

Other studies in the mCRPC space are investigating the use of 

Lu-PSMA-617 in combination with an AR inhibitor in earlier lines of therapy, Park adds. The agent is also being explored alongside other theragnostic radioligand treatments in mHSPC, Park concludes.

Chandler Park, MD, MSc, FACP, discusses how the emerging field of radiotheranostics and increasing utilization of biomarker testing will improve the treatment of patients with metastatic hormone-sensitive prostate cancer.

Chandler Park, MD, MSc, FACP

Articles

Dr Park on Navigating of Later-line Treatment Options in Metastatic Urothelial Carcinoma

Dr. Park on the Increasing Use of Biomarker Testing and Radiotheranostics in Prostate Cancer