Case Study Highlights an Approach to Adjuvant Treatment in RCC

On World Kidney Cancer Day on June 20th, 2024, Emre Yekedüz, MD, a research fellow at Dana-Farber Cancer Institute in Boston, Massachusetts, took over the OncLive^® X (formerly Twitter) account to highlight advances in treatment and spread awareness for renal cell carcinoma (RCC).

During the takeover, Yekedüz presented a case study and potential adjuvant treatment options for a patient with clear cell RCC (ccRCC).

Sixty-nine percent of responders (n = 58) chose treatment with adjuvant pembrolizumab (Keytruda); 15.5% of responders selected observation, 12.1% chose nivolumab (Opdivo), and 3.4% picked sunitinib (Sutent).

Yekedüz concurred with the majority opinion of adjuvant pembrolizumab, citing data from the phase 3 KEYNOTE-564 trial (NCT03142334) for adjuvant pembrolizumab vs placebo for patients with ccRCC.

“[Based on] the results of KEYNOTE-564, we have to consider [the application] of pembrolizumab in the adjuvant setting in [this] case,” Yekedüz said in an interview with OncLive^®.

At the 2024 Genitourinary Cancers Symposium, Toni K. Choueiri, MD, of Dana-Farber Cancer Institute, shared overall survival (OS) results of the third prespecified interim analysis of the randomized, multicenter KEYNOTE-564 study, which demonstrated that pembrolizumab treatment in the adjuvant setting significantly improved overall survival (OS) vs placebo in this patient population.¹

At a median follow-up of 57.2 months (range, 47.9-74.5), the median OS was not reached in patients in the intention-to-treat population in both the pembrolizumab (n = 496) and placebo arms (n = 498; HR, 0.62; 95% CI, 0.44-0.87; P = .002). In the pembrolizumab arm, the 12-, 24-, 36- HR, 0.62; 95% CI, 0.44-0.87; P = .002, and 48-month OS rates were 98.6%, 96.3%, 93.9%, and 91.2%, respectively. In the placebo arm, these respective OS rates were 98.0%, 93.9%, 89.5%, and 86.0%.

In November 2021, the FDA approved 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, based on prior data from KEYNOTE-564.²

In an interview, Yekedüz discussed the results of the case study presented in the X poll and expanded on approaches to adjuvant treatment for patients with ccRCC.

OncLive: What was the case study discussed in this X poll and what were the results?

Yekedüz: In this case, we had a patient [who was] a 62-year-old man, and he had pathological T3 and grade 4 ccRCC [with] sarcomatoid features. According to imaging results, there were no distant metastases in this [patient]. We asked: what would be the next step in our case in the adjuvant treatment of this patient with ccRCC?

When we look at the results from the Twitter poll, most participants selected adjuvant pembrolizumab—69% of all respondents. This is the first key takeaway of the results. This is not surprising because we know KEYNOTE-564 was the first trial that showed improved OS in [the adjuvant] setting. Previously, we knew that TKIs [were not] successful in the [adjuvant] treatment of patients with early-stage kidney cancer. [KEYNOTE-564] was the first trial that showed improvement in OS in this setting.

What other treatment options could be considered for this case?

When we look at the [National Comprehensive Cancer Network] Guidelines, based on [data from] the KEYNOTE-564 trial, we should consider adjuvant pembrolizumab first. However, sometimes our patients may have [a preexisting] autoimmune disease. We have to consider that those patients may be prone to immune-related adverse effects during pembrolizumab treatment. Therefore, we have to take into account these conditions before starting therapy. This is important in our daily clinical practice.

What might be the rationale for participants selecting one of the other three options listed in the poll for this case?

When we look at these results, I can see that some participants chose adjuvant sunitinib. We have clinical trial results that show an improvement in disease-free survival with adjuvant sunitinib; unfortunately, there is no OS benefit in this setting with adjuvant sunitinib. We should consider pembrolizumab in the adjuvant treatment of RCC.

Why is it important to discuss how a treating oncologist would approach their application methods in the adjuvant setting of ccRCC?

Because [KEYNOTE-564] was the first trial that showed an improvement in OS in the adjuvant treatment of [patients with] ccRCC, this [discussion] is important. We should evaluate our patients based on their risk groups; if they have intermediate/high- or high-risk disease, we have to consider [treatment] with pembrolizumab in the adjuvant setting.

Furthermore, [it is important to] elaborate on risk groups: intermediate/high-risk or high-risk disease. If a patient has T2, grade 4, sarcomatoid disease, or T3 disease, we can classify this patient as intermediate/high risk. If a patient has T4 and node-positive disease, we can classify this patient as having high-risk disease. On the other hand, in the metastatic setting and after metastasectomy, if there is no evidence of disease, we also should consider giving adjuvant pembrolizumab in these patients.

References

1. Choueiri TK, Tomczak P, Park SH, et al. Overall survival results from the phase 3 KEYNOTE-564 study of adjuvant pembrolizumab versus placebo for the treatment of clear cell renal cell carcinoma (ccRCC). J Clin Oncol. 2024;42(suppl 4):LBA359. doi:10.1200/JCO.2024.42.4_suppl.LBA359
2. FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma. FDA. November 17, 2021. Accessed August 21, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-renal-cell-carcinoma