Christopher W. Ryan, MD, professor of medicine, School of Medicine, the Oregon Health & Science University, discusses the role of adjuvant therapy for patients with renal cell carcinoma (RCC).

Five clinical trials have evaluated the use of a TKI in the adjuvant setting for patients with RCC; however, only 1 showed benefit, according to Ryan. The phase 3 S-TRACT trial (NCT00375674) with sunitinib (Sutent) showed that the TKI led to an improvement in disease-free survival (DFS) at 6.8 years compared with 5.6 years for placebo.

Regarding adjuvant immunotherapy, the phase 3 KEYNOTE-564 trial (NCT03142334) was the first study to produce data, Ryan notes. Updated findings reported at the 2022 Genitourinary Cancers Symposium showed that adjuvant pembrolizumab (Keytruda) elicited a statistically significant and clinically meaningful DFS benefit vs placebo in the intent-to-treat population (HR, 0.68, 95% CI: 0.53-0.87, 

 = .001). Prior data from the study supported the 

FDA approval of pembrolizumab for the adjuvant treatment of patients with RCC

 who are at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions, which added another option for patients to consider when pursuing adjuvant treatment, Ryan notes.

Although adjuvant pembrolizumab quickly established a role in clinical practice following the FDA approval, there is an absence of data regarding overall survival, Ryan explains. Additionally, using immunotherapy in the adjuvant setting could have implications for later treatment decisions if a patient relapses with metastatic disease, Ryan explains.

However, given the DFS benefit, adjuvant pembrolizumab is a reasonable treatment option for patients with RCC, Ryan says. This treatment option is something to discuss with high-risk patients following surgery, Ryan concludes.

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Christopher W. Ryan, MD, discusses the role of adjuvant therapy for patients with renal cell carcinoma.


Dr Ryan on the Role of Adjuvant Therapy in RCC

Christopher W. Ryan, MD, professor of medicine, School of Medicine at the Oregon Health & Science University, discusses the evolution of therapeutic treatment approaches across the management treatment landscape of renal cell carcinoma (RCC).

® State of the Science Summit™ on genitourinary cancers, Ryan discussed topline takeaways from the current treatment landscape of RCC. At the event, oncologists discussed first- and second-line therapy options, treatment options for patients with metastatic disease, and adjuvant approaches, Ryan begins. Data with these approaches have indicated that checkpoint inhibitor–based regimens are the standard of care for this patient population in the first-line setting, and has been shown to improve overall survival (OS) for patients with metastatic disease, Ryan expands.

When choosing an immunotherapy-based regimen for a patient with metastatic disease, there are 2 options: a checkpoint inhibitor combination of ipilimumab (Yervoy) plus nivolumab (Opdivo), or a PD-1 inhibitor with a physician’s choice TKI, Ryan explains. From additional clinical trial data and FDA approvals, there has been a documented improved overall survival (OS) benefit with the 4 different combination regimens that are currently commercially available within the RCC space, he adds.

When choosing among the treatments ipilimumab plus nivolumab, pembrolizumab (Keytruda) and axitinib (Inlyta), nivolumab and cabozantinib (Cabometyx), and pembrolizumab and lenvatinib (Lenvima), Ryan continues, it is important to note that all of the combinations have shown improvements in OS. However, it remains important to be cautious about making cross trial comparisons, as there are some differences that emerge when comparing ipilimumab and nivolumab with immunotherapy and TKI combinations, Ryan notes. Additionally, patients who have a response to ipilimumab and nivolumab seem to have durable responses as longer follow-up in the trial becomes available.

Christopher W. Ryan, MD, professor of medicine School of Medicine at the Oregon Health & Science University, discusses the evolution of therapeutic treatment approaches across the management treatment landscape of renal cell carcinoma.


Dr Ryan on the Evolution of the Treatment Landscape in RCC

Christopher W. Ryan, MD, professor of medicine, the School of Medicine at the Oregon Health & Science University, discusses the implications of updated findings from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) in patients with locally advanced or metastatic urothelial cancer.

In this trial, investigators examined maintenance immunotherapy with avelumab (Bavencio) after a response or stable disease to frontline chemotherapy, and data made this a practice-changing study, Ryan notes. The addition of avelumab to best supportive care demonstrated an improvement in overall survival (OS) compared with best supportive care alone, and in June 2020, 

the FDA approved avelumab as maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma

 that has not progressed with first-line platinum-based chemotherapy, based on findings from JAVELIN Bladder 100.

Updated data from a subgroup analysis of the trial presented at the 2023 Genitourinary Cancers Symposium further displayed the OS benefit associated with avelumab maintenance, irrespective of choice of frontline chemotherapy, Ryan explains. In patients who received a frontline chemotherapy regimen consisting of cisplatin plus gemcitabine, those in the avelumab arm had a median OS of 25.1 months (95% CI, 19.3-30.9), compared with 17.5 months (95% CI, 13.7-24.2) for those given best supporting care alone. Among patients given carboplatin plus gemcitabine as frontline chemotherapy, the median OS was 20.8 months (95% CI, 17.9-28.7) for the avelumab arm vs 13.0 months (95% CI, 9.4-16.1) for the best supportive care arm.

Notably, the median OS was higher for both the avelumab and best supportive care arms among patients who received cisplatin vs carboplatin, and it has been debated in the urothelial cancer space whether cisplatin is better than carboplatin as first-line chemotherapy, Ryan says, who notes that these findings may reflect that patients who receive carboplatin tend to have other medical comorbidities.

Given that the addition of maintenance avelumab improved OS over best supportive care, regardless of frontline chemotherapy choice, it is important to emphasize the use of maintenance immunotherapy for patients with metastatic bladder cancer who do not progress on chemotherapy, Ryan concludes.

Christopher W. Ryan, MD, discusses the implications of updated findings from the phase 3 JAVELIN Bladder 100 trial in patients with locally advanced or metastatic urothelial cancer.

Christopher W. Ryan, MD

Articles

Dr Ryan on the Role of Adjuvant Therapy in RCC

Dr Ryan on the Evolution of the Treatment Landscape in RCC

Dr Ryan on the Implications of Updated Findings from JAVELIN Bladder 100 in Urothelial Cancer