Drug Duo Sparks Encouraging Outcomes in Treatment of Clear Cell Kidney Cancer

Bavencio (avelumab) plus Inlyta (axitinib) proved to be an effective option for the neoadjuvant (presurgical) treatment of patients with high-risk, non-metastatic clear-cell renal cell carcinoma, a common type of kidney cancer, according to findings from the NeoAvAx trial presented at the 2022 ASCO GU Symposium.

In the phase 2 trial, neoadjuvant Bavencio/Inlyta induced a partial response in 12 (30%) of 40 patients. On average, patients’ primary tumors shrunk by 20%. Among patients with a partial response, 10 of 12 were disease-free at the study data cutoff.

At a median follow-up of 23.5 months, the average length of overall survival (OS; defined as how long patients live after treatment) and median disease-free survival (DFS; meaning that there are no signs of the disease) had not yet been reached since many study participants are still alive. No patients had progression of their primary tumor.

NeoAvAx is the first trial combining these types of drugs — Bavencio is an immune checkpoint inhibitor and Inlyta is a tyrosine kinase inhibitor — for this particular patient population. Since the findings were so promising, it could lead to future studies where the drug duo is compared to other standards of care for high-risk clear cell RCC.

“This is the first neoadjuvant trial reporting results from a combination of an immune checkpoint inhibitor and VEGFR-TKI for locally advanced high-risk RCC,” said lead study author Dr. Axel Bex, of the Netherlands Cancer Institute.“The DFS data are encouraging, supporting further evaluation, although currently there are no randomized neoadjuvant versus adjuvant (immune checkpoint inhibitor) trials or neoadjuvant versus adjuvant ICI/VEGFR-TKI combination (trials in this setting).”

Explaining the background of the NeoAvAx trial, Bex said, “Antibodies targeting PD-1/PD-L1 combined with VEGF inhibitors are a first-line standard of care for metastatic RCC. Neoadjuvant use of these combinations may lead to downstaging and reduce the risk of recurrence.”

Overall, there were 40 patients enrolled in the trial between May 2018 and October 2021.

The median patient age was 63 years and 70% of patients were male.

Researchers considered each patient’s World Health Organization (WHO) performance status, which ranks patients’ restrictions on a scale of 0 (no restrictions to daily life as a result of the disease/treatment) to 4 (completely disabled) and 5 (dead). The WHO performance status was 0 for 30 patients and 1 (restricted for strenuous activity but allowed to do light/sedentary work) for 10 patients.

Ninety percent of patients’ disease was classified as stage T3 or higher, indicating that the cancer has grown into major veins within the kidney or nearby tissue.

Across the population, 42.5% of patients were clinically node positive.

Patients in the trial received Inlyta at 5 mg twice daily and Bavencio at 10mg/kg every two weeks. The main goal of the study was partial response (cancer shrinking) at week 12. Secondary endpoints included DFS, OS, and safety, and biomarker analysis on sequential tissue was an exploratory end point.

Overall, 13 (32.5%) patients had disease recurrence and three patients died of disease.

Bex said there were no new side effects with the neoadjuvant regimen as compared with previously reported safety data for Inlyta and Bavencio.

The majority of side effects were considered mild or bothersome, but not serious or severe. There were six total grade 3 side effects, comprising one case each of high blood pressure, infusion-related reaction, fatigue, nausea, hand-foot syndrome (defined as redness, swelling and blistering on the palms of the hands and soles of the feet) and elevated liver function tests.

Addressing the safety profile of the subsequent surgery patients received after the neoadjuvant regimen, Bex said, “Surgical adverse events were as expected in this patient population with locally advanced RCC.”

Bex also summarized the findings from the exploratory biomarker analysis. Patients with a higher concentration of CD8+ T cells tended to have better outcomes. Now, the researchers are continuing to further investigate other tumor differences that may impact outcomes.

"Spatial transcriptomics of post-treatment primary tumor tissue revealed focal intratumoral differences in immune signatures and we are currently investigating this further to see whether this may be one of the reasons why these patients have recurrence,” Bex said.

The combination of Bavencio and Inlyta is currently Food and Drug Administration approved for the frontline treatment of patients with advanced RCC. The approval was based on results from the pivotal phase 3 JAVELIN Renal 101 trial, which showed that the combination was associated with a 31% reduction in the risk of disease progression or death compared with Sutent (sunitinib) in patients with advanced RCC that has not previously been treated.

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