Dr Badami on the Optimal Selection of Second-Line TKIs in ccRCC

“What the participants in the panel discussed was: Would you, in the second-line setting, consider adding a checkpoint inhibitor to a second-line agent? The consensus was no.”

Ami Umesh Badami, MD, medical oncologist, Endeavor Health Medical Group, discusses clinical research that has informed treatment selection in the second-line setting for patients with clear cell renal cell carcinoma (ccRCC).

 State of the Science Summit™ on genitourinary cancer, Badami and colleagues 

 of a patient with metastatic ccRCC who underwent initial nephrectomy followed by active surveillance and a frontline systemic therapy doublet. During the discussion, questions arose regarding optimal hypothetical second-line treatment options for similar cases, including whether current data signified a role for immunotherapy agents in this setting, Badami begins.

The phase 3 CONTACT-03 trial (NCT04338269), which evaluated the addition of the PD-L1 inhibitor atezolizumab (Tecentriq) to cabozantinib (Cabometyx) vs cabozantinib alone in patients with advanced RCC who had previously received an immune checkpoint inhibitor, demonstrated no benefit with the combination. Similarly, the phase 3 TiNivo-2 trial (NCT04987203), which assessed tivozanib (Fotivda) plus the PD-1 inhibitor nivolumab (Opdivo) vs tivozanib alone in patients with previously treated ccRCC, showed no significant advantages with the combination as second- or third-line therapy. The findings from these trials highlight that the addition of a checkpoint inhibitor to second-line ccRCC regimens does not improve outcomes regardless of whether the immunotherapy agent targets PD-1 or PD-L1, Badami explains.

Given these findings, the panel discussion pivoted to the selection of appropriate TKIs or alternative classes of therapy in the second-line setting, Badami says. Belzutifan (Welireg), a HIF-2α inhibitor, has shown activity in patients with ccRCC who have received 1 or more prior lines of therapy, she notes. However, this agent is predominantly used in later-line settings rather than as a second-line therapy, she emphasizes. In the presented case, cabozantinib was selected as the second-line agent, partly due to the lack of data with belzutifan at the time of treatment, she concludes.

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Ami Umesh Badami, MD, discusses clinical research that has informed treatment selection in the second-line clear cell renal cell carcinoma setting.

Dr Badami on Factors Informing Treatment Selection in ccRCC and Non–ccRCC

“Although we lump all of the non–clear cell renal cell carcinomas together, they're not actually all the same. Knowing the non–clear cell renal cell carcinoma subtype is important to help determine which regimen [to select].”

Ami Umesh Badami, MD, hematologist/oncologist, Loyola University Medical Center, discusses a variety of different factors that guide treatment decision-making for patients with clear cell renal cell carcinoma (ccRCC) vs non–ccRCC.

Histology plays a critical role in guiding treatment for non–ccRCC, a category that includes a variety of subtypes with differing responses to therapy, Badami begins. Unlike ccRCC, which has more established treatment protocols, non-clear cell RCC types like papillary and chromophobe cancers exhibit unique characteristics, impacting therapeutic choices, she says. Recent data from the phase 2 SUNNIFORECAST trial (NCT03075423) underscore these differences, with results indicating variability in response rates between these subtypes. Response rates can vary between treatment with immune checkpoint inhibitors such as ipilimumab (Yervoy) and nivolumab (Opdivo) vs investigator-selected standard-of-care regimens, Badami reports. This information highlights the importance of subtype-specific treatment strategies in non-ccRCC, she states.

In papillary RCC, the most common subtype of non–ccRCC, symptom management and response urgency further inform treatment selection, Badami continues. In symptomatic patients requiring a rapid response, immune-oncology and TKI combinations can offer more rapid disease control and potentially improve quality of life, she asserts. Meanwhile, the SUNNIFORECAST findings suggest an increasing role for ipilimumab and nivolumab in these cases, Badami reiterates. Overall, a detailed understanding of histology in non-ccRCC allows clinicians to tailor treatment, taking into account both patient symptoms and subtype characteristics. This approach can provide a more effective treatment course and reflects the increasingly nuanced landscape of RCC management, she concludes.

Ami Umesh Badami, MD, discusses the factors that guide treatment decision-making for patients with clear cell or non–clear cell renal cell carcinoma.

Dr Badami on a Case Study Illustrating Key Decisions for First-Line Metastatic RCC

Ami Umesh Badami, MD, hematologist/oncologist, Loyola University Medical Center, discusses a case study highlighting the diagnostic and therapeutic journey of a patient with metastatic clear cell renal cell carcinoma (RCC), illustrating key decision points in the management of advanced disease.

The patient initially presented with RCC and underwent nephrectomy, Badami explains. During routine surveillance, scans identified 2 lung nodules were identified, and they were retrospectively identified on earlier scans. This led to a discussion about how to approach treatment for a patient with oligometastatic disease or low-volume, indolent disease, Badami says.

She continues by noting that this particular patient's preference with treatment was to avoid unnecessary toxicity. Given that preference, treatment options focused on either local radiation therapy for the lung nodules or observation. Ultimately, the decision was made to proceed with active surveillance, Badami notes.

However, upon disease progression, first-line systemic treatment options were revisited, she continues. The first-line treatment setting for metastatic clear cell RCC has shifted significantly in recent years with immunotherapy-based combinations taking precedence, and these options were explored, Badami notes. These combinations can included dual immune checkpoint inhibitors with nivolumab (Opdivo) plus ipilimumab (Yervoy), or an immune checkpoint inhibitor in combination with a TKI, such as nivolumab plus cabozantinib (Cabometyx), pembrolizumab (Keytruda) plus lenvatinib (Lenvima), or atezolizumab (Tecentriq) plus cabozantinib.

Treatment selection often requires balancing efficacy with tolerability, Badami emphasizes. In patients with limited disease burden, such as those with oligometastatic RCC, a more conservative approach may be appropriate initially to limit adverse effects. For those with symptomatic progression, more aggressive systemic options are warranted to achieve better disease control, she concludes.

Ami Umesh Badami, MD, discusses a case study illustrating key decisions in the treatment of metastatic renal cell carcinoma.

Ami Umesh Badami, MD

Articles

Dr Badami on the Optimal Selection of Second-Line TKIs in ccRCC

Dr Badami on Factors Informing Treatment Selection in ccRCC and Non–ccRCC

Dr Badami on a Case Study Illustrating Key Decisions for First-Line Metastatic RCC