Evan Hall, MD MPhil, is a medical oncologist who specializes in the treatment of skin cancers (including melanoma) and kidney cancer.

Dr Hall on Unmet Needs in Later-Line RCC

"Right now, most of our treatments fall into a few baskets, so sometimes we’re left with uncomfortable decisions about using drugs that may interact with patient comorbidities. [Patients need] more options and [drugs with] different mechanisms, with the hope that perhaps we can find better fits for individual patients in the second- and third-line settings."

Evan T. Hall, MD, MPhil, a physician and assistant professor in the Clinical Research Division at the Fred Hutchinson Cancer Center; as well as an assistant professor at the University of Washington School of Medicine, highlighted several key unmet needs for patients with later-line renal cell carcinoma (RCC) that may be addressed by future research.

One major gap is the need for a second opportunity at achieving long-term disease control, Hall began. According to Hall, enduring remission and the potential for a treatment-free interval appear to be phenomena associated primarily with immunotherapy. He explained that although TKIs can suppress disease progression during active treatment, relapse typically occurs upon discontinuation. Thus, developing a second-line or even third-line therapy with immunomodulatory potential to induce prolonged remission could represent a significant advancement, Hall noted.

Hall also emphasized the importance of expanding therapeutic targets with differentiated toxicity profiles. Many patients with RCC are older and often present with comorbidities, such as coronary artery disease, heart failure, prior stroke, or diabetes. Hall observed that current later-line treatment options tend to cluster within a limited number of drug classes, many of which carry adverse effect profiles that may exacerbate underlying conditions. He stated that broader mechanistic diversity in available therapies could help oncologists better tailor treatment to individual patient needs, thereby improving tolerability and reducing the risk of treatment-related complications.

Ultimately, Hall concluded that the later-line RCC treatment paradigm wouldbenefit from therapies with novel mechanisms and improved safety profiles, particularly those that offer the potential for durable responses and allow for better personalization based on comorbid conditions.

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There is nuance in certain clinical scenarios, but for most patients currently treated with first-line immunotherapy-based regimens, continuing the same immune checkpoint inhibitor beyond progression does not appear to provide additional benefit."

Evan T. Hall, MD, MPhil, an oncologist at the University of Washington and Fred Hutchinson Cancer Center, provided insight into the clinical rationale and evolving evidence surrounding immune checkpoint inhibitor (ICI) continuation and rechallenge strategies in the later-line treatment of metastatic renal cell carcinoma (RCC).

In contemporary clinical practice, most patients with metastatic RCC receive frontline combination regimens containing PD-1 or PD-L1 inhibitors, either in the form of two immuno-oncology agents or an ICI combined with the TKI. As a result, determining the value of ICI continuation beyond progression—or reinitiating therapy after prior response—has become a central question in the post–first-line setting. Hall outlined data from two pivotal randomized phase 3 trials—CONTACT-03 (NCT04338269) and TiNivo-2 (NCT04987203)—that evaluated ICI-based approaches following progression on prior immunotherapy.

CONTACT-03 examined the addition of atezolizumab (Tecentriq) to cabozantinib (Cabometyx) in patients with advanced RCC previously treated with ICIs. The trial did not meet its primary end point of progression-free survival (PFS) improvement, and no benefit in overall survival (OS) was observed. Similarly, the TiNivo-2 trial assessed tivozanib with or without nivolumab in a similar patient population, again showing no incremental advantage with the addition of nivolumab. These findings, Hall explained, support the conclusion that routine continuation an ICI agent after disease progression does not confer meaningful clinical benefit.

However, Hall emphasized that certain patient subgroups may warrant more individualized consideration. For example, patients who previously experienced a durable response to ICI and have since relapsed after an extended treatment-free interval may still derive benefit from ICI rechallenge. Importantly, these scenarios were not explicitly stratified in either CONTACT-03 or TiNivo-2, leaving a gap in the data to guide optimal therapy sequencing in such settings.

Additionally, Hall discussed the limited but notable potential for alternative ICI approaches, including the use of ipilimumab (Yervoy), a CTLA-4–targeting agent, in patients who have not received it previously. Although not formally supported by randomized studies in this context, anecdotal evidence suggests clinical benefit in select cases, particularly those with immunogenic tumor features, he concluded.

Evan T. Hall, MD, MPhil, discusses the evolving evidence base surrounding ICI continuation and rechallenge strategies in the second-line treatment of metastatic renal cell carcinoma.

Evan T. Hall, MD, MPhil

Articles

Dr Hall on Unmet Needs in Later-Line RCC

Dr Hall on the Feasibility of ICI Continuation and Rechallenge Strategies in Second-Line Metastatic RCC