2. UroToday Home
  3. Conference Highlights
  4. ASCO 2025
  5. ASCO 2025 Kidney Cancer

ASCO 2025

ASCO 2025: Efficacy and Safety of Second-Line Cabozantinib +/ Atezolizumab for Patients with Advanced Renal Cell Carcinoma After Progression on Immuno-Oncology Combinations: Subgroup Analysis of CONTACT-03

(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 30th and June 3rd, 2025, was host to a kidney and bladder cancers poster session. Dr. Cristina Suárez presented a subgroup analysis of the CONTACT-03 trial evaluating the efficacy and safety of second-line cabozantinib +/ atezolizumab for patients with advanced renal cell carcinoma (RCC) after progression on immuno-oncology combinations

Cabozantinib, a vascular endothelial growth factor receptor-associated tyrosine kinase inhibitor (VEGFR-TKI), is a preferred treatment option for the second-line (2L) treatment of advanced RCC based on its superior efficacy versus everolimus;1 however, prospective data on its activity after contemporary first-line (1L) immuno-oncology (IO) combinations are limited. 

In the phase II CaboPoint trial (the only trial to date designed to prospectively evaluate the efficacy of cabozantinib after 1L IO combinations), the objective response rate (ORR) was 41% after dual IO (IO–IO) therapy and 28% after IO–TKI combination therapy; median progression-free survival (PFS) was 10.9 and 8.3 months, respectively.2 

CONTACT-03 was conducted to investigate whether adding atezolizumab to cabozantinib would improve outcomes in patients with advanced RCC who had disease progression on or after prior IO treatment.3 The results were as follows:

  • PFS by blinded independent central review (BICR), median:
    • Cabozantinib: 10.8 months
    • Cabozantinib + atezolizumab: 10.6 months
  • Overall survival, median:
    • Cabozantinib: Not estimable
    • Cabozantinib + atezolizumab: 25.7 months
  • ORR: 41% in both arms
  • Duration of response (DoR), median:
    • Cabozantinib: 14.8 months
    • Cabozantinib + atezolizumab: 12.7 months

Herein, Dr. Suárez reported the results of a subgroup analysis of the efficacy and safety of 2L cabozantinib +/- atezolizumab in patients from CONTACT-03 who received 1L treatment with US Food and Drug Administration (FDA)-approved IO–IO or IO–TKI combinations. Data from this post hoc analysis provide an opportunity to further understand the activity of 2L cabozantinib after treatment with contemporary 1L treatment regimens. 

CONTACT-03 was an open-label, randomized, phase III trial of cabozantinib versus cabozantinib + atezolizumab in adult patients with locally advanced or metastatic RCC and radiographic tumor progression on or after IO-based therapy in the adjuvant, 1L, or 2L setting.3

This unplanned, post hoc subgroup analysis included patients who had received an FDA-approved 1L IO–IO (ipilimumab + nivolumab) or IO–TKI (pembrolizumab + axitinib; avelumab + axitinib; or pembrolizumab + lenvatinib) combination prior to enrolling in CONTACT-03.

The following outcomes were analyzed for patients randomized to 2 L cabozantinib +/- atezolizumab:

  • PFS by BICR
  • OS
  • ORR
  • DoR by BICR
  • Safety

Analyses were conducted in patients who received any 1L IO combination regimen (IO–IO or IO–TKI), and for patients who received treatment with either 1L IO–IO or 1L IO–TKI.

Among patients enrolled in CONTACT-03, 107 randomized to cabozantinib alone and 129 randomized to cabozantinib + atezolizumab had received 1L treatment with one of the IO–IO or IO–TKI regimens listed earlier. Of the 107 patients in the cabozantinib group, 70 had received a 1L IO–IO regimen and 37 had received a 1L IO–TKI regimen; respective patient numbers in the cabozantinib + atezolizumab group were 80 (IO–IO) and 49 (IO–TKI). The baseline demographics and disease characteristics are provided in the table below:
Efficacy outcomes with cabozantinib and cabozantinib + atezolizumab were consistent regardless of whether patients had received prior IO–IO or IO–TKI as their 1L combination regimen, and were consistent with those observed in the intention-to-treat population of CONTACT-03.3

Among patients who had received 1L IO combination regimens, the median PFS was 10.4 months (95% CI: 8.0–12.5) for patients randomized to cabozantinib and 10.2 months (95% CI: 8.3–10.6) for patients randomized to cabozantinib + atezolizumab, respectively.
Among patients who had received 1L IO combination regimens, the median PFS was 10.4 months (95% CI: 8.0–12.5) for patients randomized to cabozantinib and 10.2 months (95% CI: 8.3–10.6) for patients randomized to cabozantinib + atezolizumab, respectively.
Similar PFS outcomes were observed among patients who received 1L IO–IO or IO–TKI regimens.
Similar PFS outcomes were observed among patients who received 1L IO–IO or IO–TKI regimens.
Among patients who had received 1L IO combination regimens, the median OS was NE (95% CI: 18.3–NE) with cabozantinib and 24.3 months (95% CI: 20.2–NE) with cabozantinib + atezolizumab.

Among patients who had received 1L IO combination regimens, the median OS was NE (95% CI: 18.3–NE) with cabozantinib and 24.3 months (95% CI: 20.2–NE) with cabozantinib + atezolizumab.
The median OS among patients who received 1L IO–IO or IO–TKI regimens is shown below:

Among patients who had received 1L IO combination regimens, the median OS was NE (95% CI: 18.3–NE) with cabozantinib and 24.3 months (95% CI: 20.2–NE) with cabozantinib + atezolizumab. 2
Among all response-evaluable patients who had received 1L IO combination regimens, the ORR was 36% and 37%, and the median DOR was 15.1 months and 10.5 months in patients randomized to cabozantinib and those randomized to cabozantinib + atezolizumab, respectively.Among all response-evaluable patients who had received 1L IO combination regimens, the ORR was 36% and 37%, and the median DOR was 15.1 months and 10.5 months in patients randomized to cabozantinib and those randomized to cabozantinib + atezolizumab, respectively.
Safety outcomes were consistent with the safety-evaluable population of CONTACT-03, irrespective of whether patients had received a 1L IO–IO or IO–TKI regimen. Among patients who had received 1L IO combination regimens, grade 3/4 treatment-related adverse events (AEs) were reported in 48% of patients treated with cabozantinib and 58% of those treated with cabozantinib + atezolizumab. Treatment-related serious AEs were reported in 13% and 25% of patients, and AEs led to dose modification in 87% and 92% of patients and to treatment discontinuation in 5% and 17% of patients, respectively.

Safety outcomes were consistent with the safety-evaluable population of CONTACT-03, irrespective of whether patients had received a 1L IO–IO or IO–TKI regimen. Among patients who had received 1L IO combination regimens, grade 3/4 treatment-related adverse events (AEs) were reported in 48% of patients treated with cabozantinib and 58% of those treated with cabozantinib + atezolizumab. Treatment-related serious AEs were reported in 13% and 25% of patients, and AEs led to dose modification in 87% and 92% of patients and to treatment discontinuation in 5% and 17% of patients, respectively.
Dr. Suárez concluded as follows:

  • Results from this post hoc subgroup analysis of CONTACT-03 suggest that 2L cabozantinib is effective in patients with advanced RCC previously treated with 1L IO combination regimens.
  • Efficacy and safety outcomes were consistent with the overall CONTACT-03 study population, regardless of whether patients had received prior treatment with IO–IO or IO–tyrosine kinase inhibitor combinations
  • The results of this analysis can help inform clinicians making 2L treatment decisions for patients with disease progression on 1L contemporary IO-containing combinations. 

Presented by: Cristina Suárez, MD, PhD, Medical Oncology, Vall d'Hebron University Hospital Barcelona, Barcelona, Spain

Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.

Related content: CONTACT-03 Subset Analysis: Similar Cabozantinib Response Across IO Pretreatment Types - Cristina Suárez

References:
  1. Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1814–23.
  2. Albiges L, Suarez C, Rottey S, et al. LITESPARK-005: a phase III trial of belzutifan vs everolimus in previously treated advanced clear cell renal cell carcinoma (ccRCC). Ann Oncol. 2024;35(Suppl_2):S1015.
  3. Pal SK, Suarez C, Agarwal N, et al. LITESPARK-005: belzutifan versus everolimus for advanced clear-cell renal cell carcinoma after immune checkpoint and VEGF-based therapies. Lancet. 2023;402:185–95.