What do the latest data mean for renal cell carcinoma treatment? We have selected six key abstracts from ESMO 2026, exploring new survival data, investigational treatment combinations and emerging therapeutic strategies.
“The kidney cancer data from ESMO 2026 send two clear messages. First, HIF-2α inhibition has a role after immunotherapy: the final LITESPARK-011 analysis confirms the benefit in progression-free survival and response for belzutifan plus lenvatinib over cabozantinib, although without a significant overall survival gain. Second, more is not always better: LITESPARK-012 showed no benefit from adding a third agent to pembrolizumab plus lenvatinib in the first-line setting. The final KEYNOTE-564 analysis further supports adjuvant pembrolizumab for patients at increased risk of recurrence after nephrectomy. Novel agents such as the PD-1/VEGF bispecific ivonescimab are promising, but still need randomised phase 3 data.” – Prof Axel Stuart Merseburger (University Hospital Schleswig-Holstein, Germany)
Which treatment strategies are improving outcomes in renal cell carcinoma (RCC), and where do investigational combinations stand? At the European Society for Medical Oncology (ESMO) Congress 2026, six selected studies examined treatment approaches across first-line advanced disease, oligometastatic RCC and adjuvant therapy: LITESPARK-011, LITESPARK-012, the ivonescimab phase Ib/II study, PE-PE, SWOG S2200 and KEYNOTE-564. The findings include sustained disease-free and progression-free survival benefits, alongside results showing that adding further agents does not necessarily improve efficacy. Together, these data offer insights into the evolving evidence base guiding treatment decisions across different RCC settings.
Advanced and metastatic kidney cancer
PE-PE: Perioperative pembrolizumab plus metastasis-directed therapy in oligometastatic RCC
Abstract: LBA88 | ClinicalTrials.gov: NCT05578664 | Phase: II
The randomized phase II PE-PE trial evaluated perioperative pembrolizumab plus metastasis-directed therapy (MDT) versus MDT alone in patients with oligometastatic RCC eligible for surgery or stereotactic ablative radiotherapy (SABR) to all metastatic sites. A total of 85 patients were randomized to pembrolizumab plus MDT (n=56) or MDT alone (n=29). After a median follow-up of 17.5 months, median relapse-free survival (RFS) was 25.4 months with pembrolizumab plus MDT versus 11.0 months with MDT alone (HR 0.47; 95% CI, 0.24–0.92; p=0.024). At least one adverse event occurred in 80% versus 21% of patients, respectively, while grade 3 adverse events occurred in 7% versus 3%.
Key clinical takeaway: Adding perioperative pembrolizumab to MDT improved RFS in this phase II study. Further evidence will help establish the durability of benefit and clarify how the combination should be used in patients with oligometastatic RCC.
LITESPARK-011: Final overall survival analysis of belzutifan plus lenvatinib
Abstract: 3587O | ClinicalTrials.gov: NCT04586231 | Phase: III
LITESPARK-011 evaluated belzutifan plus lenvatinib versus cabozantinib in patients with advanced clear cell RCC (ccRCC) following anti–PD-(L)1 therapy. At the final analysis, median progression-free survival (PFS) remained longer with belzutifan plus lenvatinib than with cabozantinib (14.8 vs 10.8 months; HR 0.74, 95% CI 0.62–0.88). Objective response rates (ORRs) were 53.1% versus 40.2%, respectively, while median duration of response was 22.0 versus 11.9 months. Median overall survival (OS) was 33.7 versus 28.6 months (HR 0.85, 95% CI 0.70–1.03). Although OS favored belzutifan plus lenvatinib, the result did not meet the prespecified significance threshold. Grade ≥3 treatment-emergent adverse events occurred in 85.4% versus 83.0% of patients.
Key clinical takeaway: The final analysis supports the sustained PFS and ORR benefits of belzutifan plus lenvatinib over cabozantinib after anti–PD-(L)1 therapy. However, the observed OS difference was not statistically significant, and grade ≥3 treatment-emergent adverse events occurred at similar frequencies in both groups.
LITESPARK-012: Adding belzutifan or CTLA-4 blockade to first-line pembrolizumab plus lenvatinib
Abstract: 3586O | ClinicalTrials.gov: NCT04736706 | Phase: III
LITESPARK-012 evaluated first-line pembrolizumab plus lenvatinib with either belzutifan or MK-1308A (coformulated quavonlimab/pembrolizumab) versus pembrolizumab plus lenvatinib alone in patients with untreated advanced clear cell renal cell carcinoma (ccRCC). Among 1,688 randomized patients, neither investigational combination improved PFS or OS. In the overall population, median PFS was 20.8 months with belzutifan, 20.7 months with MK-1308A and 23.7 months with pembrolizumab plus lenvatinib alone. The hazard ratios for PFS versus control were 1.08 (95% CI 0.93–1.26; p=0.84) and 1.07 (95% CI 0.92–1.25; p=0.82), respectively. Median OS was 52.0 months with belzutifan and not reached in the other two arms. Grade ≥3 adverse events occurred in 87.2%, 88.7% and 84.8% of patients, respectively, while adverse events led to discontinuation of any study drug in 51.6%, 51.4% and 36.2%.
Key clinical takeaway: Neither the addition of belzutifan nor CTLA-4 blockade improved PFS or OS over pembrolizumab plus lenvatinib. The higher rates of treatment discontinuation in the investigational arms may have limited drug exposure and partly affected efficacy. The findings support pembrolizumab plus lenvatinib as a first-line standard-of-care option in this setting.
Ivonescimab: First-line PD-1/VEGF bispecific antibody in favorable-risk advanced RCC
Abstract: 3592O | ClinicalTrials.gov: NCT06472895 | Phase: Ib/II
This open-label, single-arm study evaluated ivonescimab (AK112), a PD-1/VEGF-A bispecific antibody, as first-line monotherapy in patients with untreated advanced ccRCC and International Metastatic RCC Database Consortium (IMDC) favorable-risk disease. By April 27, 2026, 26 patients had been enrolled, with tumor assessments available for 21 patients. At a median follow-up of 9.1 months, the ORR was 57.1%, including 12 partial responses, and the disease control rate was 95.2%. Median PFS was not reached, and the 12-month and 18-month PFS rates were both 87.9%. Grade ≥3 treatment-related adverse events occurred in 26.9% of patients. No treatment-related deaths were reported.
Key clinical takeaway: The findings provide preliminary evidence of antitumor activity with first-line ivonescimab monotherapy in IMDC favorable-risk advanced ccRCC. The small, single-arm study and limited follow-up mean that the durability of benefit and longer-term survival outcomes require further evaluation.
SWOG S2200: Cabozantinib with or without atezolizumab in metastatic papillary RCC
Abstract: 3591RO | ClinicalTrials.gov: NCT05411081 | Phase: II
SWOG S2200 compared cabozantinib with cabozantinib plus atezolizumab in patients with metastatic papillary RCC. The study was terminated in January 2026 because of poor accrual, with 36 patients enrolled and 33 deemed eligible. After a median follow-up of 24 months, median PFS favored the combination (HR 0.46; 90% CI, 0.22–0.97; one-sided p=0.043). OS was not significantly improved (HR 1.67; 90% CI, 0.59–4.7; one-sided p=0.79). Grade 3/4 adverse events occurred in 65% of patients receiving cabozantinib plus atezolizumab and 75% receiving cabozantinib alone.
Key clinical takeaway: The study reported a statistically significant PFS improvement with cabozantinib plus atezolizumab at the prespecified nominal significance level. However, the substantially lower-than-anticipated accrual and small sample size limit interpretation, and no significant OS improvement was demonstrated. Further evidence is needed to clarify the role of checkpoint inhibitor combinations in metastatic papillary RCC.
Adjuvant treatment
KEYNOTE-564: Final analysis of adjuvant pembrolizumab in clear cell RCC
Abstract: 3589RO | ClinicalTrials.gov: NCT03142334 | Phase: III
KEYNOTE-564 evaluated adjuvant pembrolizumab versus placebo in patients with ccRCC at increased risk of recurrence following nephrectomy, with or without metastasectomy. At the final protocol-prespecified analysis, median follow-up was 85.9 months. Median disease-free survival (DFS) was not reached with pembrolizumab versus 68.3 months with placebo (HR 0.68; 95% CI 0.56–0.82). Seven-year DFS rates were 57.2% versus 44.6%, respectively. Median OS was not reached in either group (HR 0.70; 95% CI 0.53–0.92), while 7-year OS rates were 82.3% with pembrolizumab and 76.6% with placebo. No new serious treatment-related adverse events were reported.
Key clinical takeaway: The final analysis showed sustained DFS and OS benefits with adjuvant pembrolizumab, consistent with earlier reports. The findings continue to support adjuvant pembrolizumab as a standard treatment for patients with ccRCC at increased risk of recurrence following surgery.
This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the European Society for Medical Oncology (ESMO). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media. This article was created by the editorial team utilizing AI as an editorial tool (Claude.AI and ChatGPT 5.5). The content was developed and edited by human editors. No funding was received in the publication of this article.
Cite: ESMO 2026 RCC round-up: The key clinical trials shaping treatment. touchONCOLOGY. 28th October 2026.
Editor: Sophie Nickelson
