Subsequent Therapy Shows No Difference in OS Following IO/TKI-Based Treatment in RCC

Neil J. Shah, MBBS

TKIs with or without an immuno-oncology (IO)-based treatment were the preferred line of second- or later-line treatment in patients with metastatic renal cell carcinoma (RCC) following progression on IO- and TKI-based therapies, but no overall survival (OS) differences were noted between regimens, according to data presented in a poster at the 2024 Kidney Cancer Research Summit.¹

Investigators evaluated real-world treatment sequences and clinical outcomes of patients with metastatic RCC post-IO and -TKI therapy (n = 820) in a comprehensive analysis of data garnered from The US Oncology Network iKnowMed™ database. Although cabozantinib (Cabometyx) was used most commonly across all treatment lines (35.6%), everolimus (Afinitor) plus lenvatinib (Lenvima; 9.5%) and ipilimumab (Yervoy) plus nivolumab (Opdivo; 7.4%) were also commonly used across all lines of therapy. However, OS with these treatments varied, at 19.2 months (95% CI, 16.1-24.4), 12.6 months (95% CI, 7.9-17.9), and 27.6 months (95% CI, 13.3-not evaluable), respectively.

“This real-world study [evaluated] the post-IO/TKI space [in which] there are a lot of agents [present]. Our study suggests that we do not have a clear [answer of whether] one agent is superior to other agents,” stated Neil J. Shah, MBBS, genitourinary medical oncologist at Memorial Sloan Kettering Cancer Center (MSK) in New York, New York.

In an interview with OncLive®, Shah, who also serves as an assistant attending physician at MSK, discussed the real-world clinical outcomes of patients with metastatic RCC receiving treatment in the post-IO and -TKI setting, highlighted the key outcomes of this investigation, and expanded on unanswered questions that remain within the treatment landscape.

OncLive: How have modern frontline regimens affected treatment sequencing in advanced RCC? How does this relate to your presentation at the 2024 Kidney Cancer Research Summit?

Shah: The kidney cancer treatment landscape is rapidly changing. We have many new treatment regimens in kidney cancer, especially within the first-line setting. Now, the question is, ‘What happens after a patient receives these modern first-line agents, including IO/IO and IO/TKI [treatment]?’ What agents are they receiving in the next line [and what is their activity]? This was the rationale for our study, [which we presented] in a poster [at the meeting].

What patient characteristics do you consider when choosing between dual IO or VEGF-based treatment regimens?

This is a very interesting question [because] the short answer is that it’s not clearly defined. The long answer is that there are a lot of patient nuances when choosing first-line IO/IO agents vs IO/TKI agents. The biggest strength for IO/IO [treatment] is the long-term survival, [which we see in the] tail of the curve. It has shown the best long-term outcome data, especially for a subset of patients who respond to this treatment.

[Although an] IO/TKI regimen is a very good treatment, it has shown that its strength is deep, fast-onset responses, [whereas an] IO/IO regimen takes a little bit longer [to elicit a response]. There are some patient nuances though. If the patient has very high-volume disease, a lot of pain, or is symptomatic, we may choose IO/TKI agents compared with an IO/IO regimen.

Please describe the population that was included in the study that you presented at the meeting.

This was a real-world retrospective study where we looked at clinical outcomes [of patients treated by] community oncologists across diverse geographic regions in the United States. We looked at patients’ outcomes post IO and TKI treatment either in combination or in sequence.

What findings were derived from this investigation?

We noted a diverse pattern of agents used in this setting, with cabozantinib [Cabometyx] being one of the most common drugs [that was used]; a lot of combinations were used as well, including IO/TKI combinations. What we noted, to our surprise, is that there was no 1 agent that was superior. There was no difference in OS [despite the] diverse use of agents in this setting, which was a very interesting finding.

Overall, most of the patients’ median survival was 6 months or less, suggesting that we need novel agents in the post-IO/TKI setting to improve patient outcomes. Those were [the] 2 major findings from our [study].

Based on this research in what setting do patients stand to gain the most from investigational novel agents?

IO and TKI [agents] are the key backbones of treatment in kidney cancer. Most patients will have received either IO/IO combinations or IO/TKI combinations in the first-line setting. How we can get an improved outcome in patients whose disease progresses on these treatments is an unmet need.

In our study, we found that most of patients [who are] post-IO/TKI therapy have limited survival. [To address] this we [need to] find novel agents and improve the survival of these patients in the [second line and beyond]. That’s the need that we have right now, and the field is rapidly evolving. We have new agents coming into this field, and we are excited about it.

What would you like your colleagues in the community setting to understand about this study?

In community practices we are noticing that people are using lot of these different agents in different combinations, which is appropriate. We need further studies to define this space and identify what the best strategies are for treatment in this space.

The message to community oncologists is that this is exciting; we can study this landscape post-IO/TKI therapy. [It also] suggests that many patients are receiving multiple lines of treatment for kidney cancer. This is great news. We have many treatments now for [patients with] kidney cancer, and most of our patients should be able to get multiple lines of treatment. This space is rapidly evolving, so we have new drugs coming, and we are looking forward to that.

Reference

Shah NJ, Sura S, Shinde R, et al. Real-world treatment patterns and clinical outcomes of metastatic renal cell carcinoma patients (mRCC) post immune-oncology (IO) and vascular endothelial growth factor (VEGF) receptor targeted therapies. Presented at: 2024 Kidney Cancer Research Summit; July 11-12, 2024; Boston, MA. Abstract 36.