RCC Research May Lead to SOC Improvements and Individualized Treatment Plans

Although immunotherapy (IO)/TKI combinations are at the forefront of renal cell carcinoma (RCC) management, additional research is necessary to determine optimal treatment sequencing with these drug classes and discover the appropriate timing of administering subsequent lines of therapy, according to Marijo Bilusic, MD, PhD. 

“Our major mission as academic oncologists is to try to educate patients that well-conducted clinical trials are always the correct answer,” Bilusic said in an interview with OncLive® following a State of the Science Summit on prostate cancer and RCC, which he chaired. Bilusic is the GU site disease group lead and the GU SDD medical oncology lead at the University of Miami Miller School of Medicine and the Sylvester Comprehensive Cancer Center in Florida.

In the interview, he highlighted key insights about RCC that were presented at the meeting covering considerations on sequencing TKIs, the need for further research to elucidate novel therapies, and the importance of offering clinical trials to all patients with genitourinary (GU) malignancies.

Bilusic noted that updated data with pembrolizumab (Keytruda) plus lenvatinib (Lenvima) in patients with non–clear cell RCC (ccRCC) are encouraging yet leave room for further treatment advances for this population. In the single-arm, phase 2 KEYNOTE-B61 trial (NCT04704219), the combination elicited a confirmed objective response rate of 49% (95% CI, 41%-57%) in patients with advanced non-ccRCC (n = 158) including a 6% complete response rate and 44% partial response rate.1 He also emphasized the clinical implications of the findings from the TIVO-3 trial (NCT02627963), in which patients who received tivozanib (Fotivda; n = 175) achieved a median progression-free survival of 5.6 months (95% CI, 5.29-7.33) vs 3.9 months (95% CI, 3.71-5.55) for those given sorafenib (Nexavar; n = 175;HR, 0.73; 95% CI, 0.56-0.94; P = .016).²

OncLive: Your colleague, Jaime Rafael Merchan, MD, of Sylvester Comprehensive Cancer Center, discussed a case study of a patient with non-ccRCC. What does this case spotlight about the management of this disease?

Bilusic: With non-ccRCC, the key message is always that we want to have patients on clinical trials. [Dr Merchan presented an update with] lenvatinib plus pembrolizumab [in this population], showing that there are benefits [with this regimen] for a subset of patients. However, more research is always needed. It’s good to have the data. We have cabozantinib [Cabometyx], lenvatinib, and pembrolizumab as treatment options for these patients, but there are no groundbreaking, dramatic changes in the treatment options we have currently.

Dr Merchan also discussed the frontline use of IO/TKI combinations in advanced and metastatic RCC. How do these combinations fit into the treatment paradigm for this patient population?

IO/TKI combinations are becoming the standard of care [SOC] and more of us are using those as our preferred frontline options. [These combinations are] approved across the board for patients with poor-risk, intermediate-risk, and good-risk RCC. One can argue which treatment combination is better—each of us has a favorite.

[However], based on our participation in clinical studies, as with PARP inhibitors, I don’t think one [IO/TKI combination] is better than another. It’s good to have them available, and they should be the SOC across the board. Most of our oncology colleagues who care for patients with kidney cancer will prescribe IO/TKI combinations that are currently available and approved for the treatment of these patients.

Pasquale W. Benedetto, MD, of the University of Miami Miller School of Medicine, discussed treatments for patients with advanced or metastatic RCC in the second line and beyond. What is the importance of considering second-line treatment options for these patients?

With IO/TKI combination upfront therapy, the second line of therapy becomes more challenging to select. Dr Benedetto suggested that [in the second-line setting], we transition to using whatever TKI we didn’t use in the frontline setting vs using a combination of lenvatinib plus everolimus [Afinitor]. He also discussed tivozanib as a third-line preferred option. [Findings from] the phase 3 [TIVO-3] study indicate that this [agent] is effective and should be offered to our patients.

Dr Benedetto was also surprised when he was reviewing data that only a fraction of patients [enrolled in] the clinical trial received second-line therapy. This is not typically what we see in our practices, because in our practices, we tend to scan patients more frequently, [and if] they progress, we can try [subsequent] lines of therapy. Across all the clinical trials [that Dr Benedetto discussed] only approximately 60% of patients received second-line therapy, which is surprising. One would think that all patients with kidney cancer receive second-line therapy. In reality, only approximately 60% [of patients do], which [indicates] that we should do a better job of changing the treatments, scanning patients early, or maybe offering second-line therapy to all patients. All patients should have second-line therapy.

What is the importance of conducting a range of clinical trials and offering trial opportunities to patients?

We do a lot of research at the Sylvester Comprehensive Cancer Center. Some studies are in early stages, and we cannot talk openly about them. We have approximately 20 different studies for prostate, bladder, and kidney cancers. At our institution, we try to have a clinical trial for every single disease state, such as castration-resistant prostate cancer and castration-sensitive prostate cancer.

We all agree that clinical trials are the best [treatment plans to] offer to patients, and we like to have trials for every single patient who comes to see us. Whatever trial portfolio we have, when patients come to see us and talk to us, we should discuss clinical trials. This is an important message that we have to deliver because few patients want to participate in trials.

References

1. Albiges L, Gurney H, Atduev V, et al. Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2023;24(8):881-891. doi:10.1016/S1470-2045(23)00276-0
2. Rini BI, Pal SK, Escudier BJ, et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020;21(1):95-104. doi:10.1016/S1470-2045(19)30735-1