Dr Sharma on the Clinical Utility of Enfortumab Vedotin Plus Pembrolizumab in Bladder Cancer

Janaki Neela Sharma, MD, assistant professor, clinical medicine, Genitourinary Medical Oncology, University of Miami Health Systems, discusses the clinical significance of the FDA approval of enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) for patients with locally advanced or metastatic urothelial cancer.

this combination for the treatment of patients in this population

based on findings from the randomized, open-label, phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856). During the original presentation of the trial data, the findings received a standing ovation because of the high response rates, durable responses, and overall survival benefits, which were impressive, especially for bladder cancer, where such results are rare, Sharma begins. Initially, enfortumab vedotin plus pembrolizumab 

 for patients ineligible for cisplatin, creating a unique scenario where cisplatin-ineligible patients were eligible to receive this effective treatment but cisplatin-eligible patients were not, she states. This accelerated approval was a significant first step, offering remarkable outcomes for patients who otherwise had limited treatment options, Sharma reports.

With expanded approval now covering all patients with metastatic disease, regardless of cisplatin eligibility, enfortumab vedotin plus pembrolizumab has become a favored first-line regimen due to its manageable adverse effect profile, she continues, noting that this, however, raises questions regarding optimal sequencing for second-line treatments and beyond. Specifically, response rates with traditional chemotherapy, such as cisplatin and gemcitabine, following enfortumab vedotin plus pembrolizumab, remain unclear, Sharma emphasizes.

Sharma states that another key issue is whether the combination of enfortumab vedotin and pembrolizumab as first-line therapy is superior to 

the nivolumab (Opdivo) plus cisplatin and gemcitabine combination

. Although preliminary data with the enfortumab vedotin and pembrolizumab combination are promising, showing better outcomes compared with nivolumab plus cisplatin and gemcitabine, there is still a need for direct, head-to-head comparisons to definitively establish superiority of one regimen over the other, Sharma says. Until such data are available, evidence-based practitioners may remain cautious, awaiting robust comparative data to confirm these findings and optimize treatment pathways for metastatic bladder cancer, she concludes.

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Janaki Neela Sharma, MD, discusses the FDA approval of enfortumab vedotin plus pembrolizumab for patients with locally advanced/metastatic bladder cancer.

Dr Sharma on Questions Regarding the Optimal Use of Triplet Therapies in HSPC

Janaki Neela Sharma, MD, assistant professor, genitourinary oncology, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses data on the use of triplet therapies in patients with hormone-sensitive prostate cancer (HSPC), highlighting unanswered questions regarding triplet vs doublet treatment options for patients whose disease is not considered high risk.

The phase 3 PEACE-1 (NCT01957436) and ARASENS (NCT02799602) trials demonstrated the survival benefit associated with adding an androgen receptor pathway inhibitor (ARPI) to standard-of-care (SOC) therapy vs SOC alone for patients with prostate cancer, Sharma says. PEACE-1 evaluated treatment with SOC (n = 296; defined as androgen deprivation therapy [ADT] alone or in combination with docetaxel) vs SOC plus radiotherapy (n = 291) vs SOC plus abiraterone acetate (Zytiga; n = 292) vs SOC plus radiotherapy and abiraterone (n = 291) in patients with metastatic castration-resistant prostate cancer.

In the overall population, at a median follow-up of 3.5 years (IQR, 2.8-4.6), the median radiographic progression-free survival was longer among patients who received abiraterone (n = 583) than those who did not receive abiraterone (n = 589; HR, 0.54; 99.9% CI, 0.41-0.71; 

 < .0001). At a median follow-up of 4.4 years (IQR, 3.5-5.4), the median overall survival (OS) was longer among patients treated with abiraterone vs those not treated with abiraterone (HR, 0.75; 95.1% CI, 0.59-0.95; 

The ARASENS trial randomly assigned patients with metastatic HSPC to receive either darolutamide (Nubeqa; n = 651) or placebo (n = 655), both in combination with docetaxel and ADT. The addition of darolutamide to docetaxel and ADT reduced the risk of death by 32.5% vs placebo (HR, 0.68; 95% CI, 0.57-0.80; 

 < .001). The 4-year OS rates in the darolutamide and placebo arms were 62.7% (95% CI, 58.7%-66.7%) and 50.4% (95% CI, 46.3%-54.6%), respectively.

Although both PEACE-1 and ARASENS met their primary end points, these trials were not designed to determine whether docetaxel plus an ARPI is superior to an ARPI alone in patients with HSPC, Sharma explains. Therefore, the optimal treatment for patients with HSPC who do not have high-risk disease remains unclear, Sharma emphasizes. Ongoing and planned studies are investigating which patients with HSPC should receive a triplet regimen and which will receive a doublet regimen, Sharma concludes.

Janaki Neela Sharma, MD, discusses data with triplet therapies in patients with hormone-sensitive prostate cancer.

Janaki Neela Sharma, MD

Articles

Dr Sharma on the Clinical Utility of Enfortumab Vedotin Plus Pembrolizumab in Bladder Cancer

Dr Sharma on Questions Regarding the Optimal Use of Triplet Therapies in HSPC