Neoadjuvant Tislelizumab Plus Axitinib Generates Responses in Locally Advanced ccRCC

Neoadjuvant treatment with the combination of tislelizumab (Tevimbra) and axitinib (Inlyta) demonstrated clinical efficacy and a manageable safety profile in patients with nonmetastatic clear cell renal cell carcinoma (ccRCC), according to data from a single-center, phase 2 trial (NCT05172440) presented at the 2024 Genitourinary Cancers Symposium.¹

Findings showed that patients evaluable for efficacy (n = 10) experienced an investigator-assessed confirmed objective response rate (ORR) of 50%. At 12 weeks, 10% had a complete response, 40% had a partial response, 40% had stable disease, and 10% had progressive disease. The disease control rate was 90%, and no patients experienced disease recurrence.

“As a neoadjuvant therapy for ccRCC, the combination of tislelizumab and axitinib had clinical efficacy and a manageable safety profile,” lead study author Shun Zhang, MD, of the Department of Urology of Affiliated Drum Tower Hospital, Medical School of Nanjing University, and the Institute of Urology at Nanjing University in China, and colleagues, wrote in a poster presentation of the data.

Although the combination of PD-1/PD-L1 inhibition and VEGF inhibition has improved survival for patients with advanced ccRCC, the role of perioperative application of this strategy in patients with localized RCC has yet to be established. Therefore, investigators investigated the safety and efficacy of tislelizumab plus axitinib in downsizing tumors in patients with nonmetastatic disease prior to surgical resection.

The prospective study enrolled patients at least 18 years of age and no older than 75 years of age with high-risk, locally advanced ccRCC who were candidates for partial or complete nephrectomy. Other key inclusion criteria consisted of clinical stage cT2-T4, N0-1, and M0 tumors; no prior systemic therapy for RCC; an ECOG performance status of 0 or 1; and normal hematopoiesis and organ function.^1,2

Eligible patients were enrolled to receive neoadjuvant combination therapy of tislelizumab at 200 mg once every 3 weeks and axitinib at 5 mg twice daily prior to nephrectomy. Following the completion of 12 weeks of treatment, patients underwent surgery within 6 weeks. Notably, radiological evaluations were performed at weeks 6 and 12 of neoadjuvant therapy.¹

The primary end point of the study was ORR following neoadjuvant therapy per RECIST v1.1 criteria. Secondary end points included disease-free survival, overall survival, surgical outcomes, and safety.

As of September 2023, 13 eligible patients were enrolled onto the trial; 11 completed neoadjuvant therapy, and 9 of these patients underwent surgery without any delay. One patient discontinued the study due to disease progression and treatment with further systemic therapy, and another patient due to concomitant treatment.

The median age of patients who completed neoadjuvant treatment was 60 years (range, 45-73). The majority of this population was female (55%), and 73% of patients had an ECOG performance status of 0. Primary tumor stage included T2a (9%), T3a (55%), T3b (18%), and T4 (18%). Notably, 64% of patients had a regional lymph node stage of N1. The mean baseline tumor diameter was 10.1 cm (range, 5.8-12.6).

Regarding safety, the most common treatment-related adverse effects (TRAEs) included hematologic toxicities, hypothyroidism, nausea, vomiting, decreased appetite, fatigue, diarrhea, and elevated alanine aminotransferase/aspartate aminotransferase. Notably, there were no grade 4 or grade 5 TRAEs, and no direct intraoperative complications or drug-related, postoperative surgical complications were recorded.

References

1. Zhang S, Ji C, Liu G, Guo H. A phase II study of neoadjuvant tislelizumab and axitinib in patients with locally advanced non-metastatic clear cell renal cell carcinoma (ccRCC). J Clin Oncol. 2024;42(suppl 4):420. doi:10.1200/JCO.2024.42.4_suppl.420
2. A study on the safety and effectiveness of tislelizumab combined with axitinib for neoadjuvant treatment of ccRCC. ClinicalTrials.gov. Updated December 29, 2021. Accessed March 1, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05172440