Updated Data Support Axitinib Interruption and Avelumab Maintenance After Response in Advanced RCC

Updated findings from the phase 2 TIDE-A study (NCT04698213) presented at the 2025 Genitourinary Cancers Symposium further demonstrated the feasibility of continuing avelumab (Bavencio) as maintenance and interrupting axitinib (Inlyta) in previously untreated patients with metastatic renal cell carcinoma (RCC) who achieved a response when receiving the 2 agents as combination frontline therapy.1

Findings showed that at a median follow-up of 31.7 months, patients in the overall population (n = 75) achieved a median progression-free survival (PFS) of 27.9 months (95% CI, 23.0-32.8). The median overall survival (OS) was not reached (NR), and the 24-month OS rate was 85%.

Among the patients who interrupted axitinib at week 36 (n = 29), the median PFS and OS were both NR; the 24-month PFS and OS rates were 58% and 82%, respectively. The median duration of first avelumab maintenance was 16 weeks.

“This analysis with a longer follow-up confirmed the feasibility of VEGFR TKI interruption and the high response rate after VEGFR TKI reintroduction in patients receiving avelumab maintenance,” lead study author Daniela Arduini, MD, of Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, and colleagues wrote in a poster presentation of the data.

Following axitinib interruption, 5 patients remained on avelumab monotherapy without disease progression. One patient discontinued avelumab due to adverse effects after 35.8 months of maintenance. Two patients continued avelumab despite evidence of disease progression, and 21 patients restarted axitinib.

Among patients who restarted axitinib, the objective response rate (ORR) was 50%, with partial responses (PR) in 10 patients, stable disease in 8 patients, and progressive disease in 2. The median PFS following axitinib reintroduction was 17.2 months (95% CI, 11.9-22.5).

“The progression during maintenance with [avelumab] alone did not affect the response to the subsequent TKI reintroduction. This strategy warrants further investigation in a randomized trial,” study authors added.

Trail Enrollment Criteria and Design

TIDE-A enrolled patients with metastatic RCC who had measurable disease, an ECOG performance status of 0 or 1, no bulky or symptomatic disease, and no hepatic metastases.

Patients were excluded if they received prior systemic therapy for advanced RCC; received prior adjuvant or neoadjuvant treatment; had an active seizure disorder or evidence of active brain metastases, spinal cord compression, or carcinomatous meningitis; or had a history of another malignancy within 2 years prior to enrollment, with the exception of adequately treated non-melanoma skin cancer or carcinoma in situ.2

All enrolled patients initially received combination therapy with avelumab at 800 mg once every 2 weeks plus axitinib at 5 mg twice per day for 36 weeks. At week 36, patients underwent tumor evaluation, and those who achieved a PR—defined as a tumor volume reduction of at least 30% from baseline—discontinued axitinib and continued avelumab monotherapy at 800 mg once every 2 weeks until disease progression.1,2

If disease progression occurred during avelumab maintenance—defined as a tumor volume increase of at least 20% from the week 36 assessment—axitinib was reintroduced at the same dose and discontinued again upon patients achieving a new PR.1,2 Patients who had stable disease at week 36 continued combination therapy until disease progression.1 Those with progressive disease at week 36 stopped all treatment.

The trial’s primary end point was ORR at 8 weeks following axitinib discontinuation and initiation of avelumab maintenance after 36 weeks of combination therapy.2 Secondary end points included PFS, ORR for the combination period, disease control rate, OS, safety, and patient-reported outcomes.

References

1. Arduini D, Cicciarese C, Acunzo A, et al. Updated results of the TIDE-A study evaluating avelumab plus intermittent axitinib in previously untreated patients with metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2025;43(suppl 6):551. doi:10.1200/JCO.2025.43.6_suppl.551
2. Avelumab plus intermittent axitinib in previously untreated patients with metastatic renal cell carcinoma (TIDE-A). Updated January 6, 2021. Accessed February 15, 2025. https://clinicaltrials.gov/study/NCT04698213