Comparison of Cabozantinib and Axitinib as Second-line Therapy After Nivolumab Plus Ipilimumab in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Comparative Analysis of Retrospective Real-world Data.

BACKGROUND: To date, no studies have compared the treatment outcomes of second-line therapies in patients with metastatic clear cell renal cell carcinoma (ccRCC). This study retrospectively evaluated the efficacy of cabozantinib and axitinib as second-line treatments in patients with metastatic ccRCC who previously received immune-oncology combination therapy. PATIENTS AND METHODS: Patients with metastatic ccRCC treated with cabozantinib and axitinib as second-line therapy after nivolumab-ipilimumab treatment were identified among 243 patients with RCC treated between August 1, 2018 and January 31, 2022 at 34 institutions belonging to the Japanese Urological Oncology Group. Patients were assessed for treatment outcomes, including progression-free survival (PFS), overall survival, objective response rate (ORR), and incidence rate of treatment-related adverse events (AEs). RESULTS: Forty-eight patients treated with cabozantinib and 60 treated with axitinib as second-line therapy after nivolumab-ipilimumab treatment for metastatic ccRCC were identified. The median PFS (95% confidence interval) was 11.0 months (9.0-16.0) with cabozantinib and 9.5 months (6.0-13.0) with axitinib. The ORRs were 37.5% (cabozantinib) and 38.3% (axitinib). The rates of any-grade AEs and grade ≥3 AEs were 79.2% (cabozantinib) versus 63.3% (axitinib; P = .091) and 35.4% (cabozantinib) versus 23.3% (axitinib; P = .202), respectively. In the poor-risk group, PFS was longer in the cabozantinib group than in the axitinib group (P = .033). CONCLUSION: The efficacy and safety of cabozantinib and axitinib were comparable. In the poor-risk group, cabozantinib was more effective than axitinib. These findings provide valuable insights into the selection of second-line treatment options after nivolumab-ipilimumab treatment in patients with metastatic ccRCC.

Multiorgan failure caused by pembrolizumab and axitinib in a woman affected by metastatic clear cell renal cell carcinoma: A case report and literature review.

RATIONALE: Treatment with a combination of immune checkpoint inhibitors (ICIs) (pembrolizumab or nivolumab) and oral Tyrosine Kinase Inhibitors (TKI) targeting angiogenesis (axitinib, cabozantinib or lenvatinib) has shown benefits in terms of efficacy and survival in metastatic renal cell carcinoma (mRCC), with a favorable toxicity profile. However, some rare and serious treatment-related adverse events can be difficult to manage. PATIENT CONCERNS: Here we report the first case of an mRCC patient who, after only 2 administrations of pembrolizumab-axitinib, experienced severe multiorgan failure (MOF) with heart failure, oliguria and acute hepatitis requiring aggressive supportive treatment in intensive care unit. DIAGNOSES: A diagnosis of severe MOF induced by pembrolizumab plus axitinib was considered. INTERVENTIONS: The patient was treated with dobutamine, levosimendan along with high-dose steroids under continuous cardiologic monitoring. OUTCOMES: After treatment, the patient had a full recovery and was discharged from the hospital. LESSONS: We reviewed all the other cases of MOF reported during treatment with combined ICI-TKI in cancer patients in order to summarize incidence, clinical manifestations and management with a specific focus on the need for prompt recognition and aggressive management under multidisciplinary care.

Influence of genetic polymorphisms in vascular endothelial-related genes on the clinical outcome of axitinib in patients with metastatic renal cell carcinoma.

OBJECTIVE: Axitinib is an oral multi-target tyrosine kinase inhibitor used for the treatment of renal cell carcinoma (RCC). Because of the severe adverse events (AEs) associated with axitinib, patients often need dose reductions or discontinue its use, highlighting the need for effective biomarkers to assess efficacy and/or AEs. The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in genes involved in the pharmacodynamic action of axitinib and clinical prognosis and AEs in metastatic RCC (mRCC) patients. METHODS: This study included 80 mRCC patients treated with first-, second-, or third-line axitinib (5 mg orally twice daily). Clinical parameters and genetic polymorphisms were examined in 75 cases (53 males and 22 females). We assessed three SNPs in each of three candidate genes namely, angiotensin-converting enzyme (ACE), nitric oxide synthase 3 (NOS3), and angiotensin II receptor type 1 (AT1R), all of which are involved in axitinib effects on vascular endothelial function. RESULTS: Axitinib-treated patients carrying the ACE deletion allele suffered more frequently from hand-foot syndrome and a deterioration in kidney function (p = .045 and p = 0.005, respectively) whereas those carrying the NOS3 G allele suffered more frequently from proteinuria and multiple AEs (p = .025 and p = 0.036, respectively). CONCLUSIONS: Our study found that the ACE deletion allele and the NOS3 G allele are associated with increased AEs.

Axitinib en el tratamiento del cáncer renal metastásico en la vida real, análisis de nuestros resultados / Axitinib in real life, analysis of our results

Objetivo: Tras progresión de primera línea de tratamiento en el carcinoma renal metastásico hay disponibles distintas opciones de tratamiento de segunda línea, siendo Axitinib una de ellas. Métodos: Desde diciembre de 2011 hasta octubre de 2016, hemos tratado a 19 pacientes con CCRm con Axitinib, 3 pacientes en tercera línea y 16 en segunda línea tras progresión de Sunitinib o Pazopanib. Realizamos un estudio retrospectivo de los últimos 16 pacientes, analizando efectividad y seguridad del fármaco. Resultados: La mediana de la supervivencia libre de progresión (SLP) fue de 9 meses y la mediana de supervivencia global con 8 pacientes fallecidos fue de 59 meses. La toxicidad global por Axitinib fue muy frecuente, diarrea 87,5%, astenia 75%, disfonía 56,25%, HTA 37,5% y anorexia 37,5%, aunque en su mayoría fueron toxicidades grado 1-2 controlados con medidas higiénico dietéticas y recomendaciones de tratamiento. Conclusiones: Axitinib es un fármaco que ha demostrado aumentar la SLP tras progresión de 1 línea, con un perfil toxico tolerable. Con la aprobación de nivolumab y cabozantinib, el lugar de Axitinib en la terapia secuencial está por definir

Objective: Following first-line treatment progression in metastatic renal carcinoma, different options for second-line treatment are available, with axitinib being one of them. The objective of this article is to evaluate the results of Axitinib in a real practice setting. Methods: From December 2011 to October 2016, we treated 19 patients with CCRM with Axitinib, 3 patients in third line and 16 patients in second line after progression on Sunitinib or Pazopanib. We performed a retrospective study of the last 16 patients, analyzing the effectiveness and safety of the drug. Results: The median progression-free survival (PFS) was 9 months and the median overall survival with 8 dead patients was 59 months. Overall, toxicity by Axitinib was very common, diarrhea 87.5%, asthenia 75%, dysphonia 56.25%, hypertension 37.5% and anorexia 37.5%, although most are grade 1-2 toxicities controlled with hygiene-diet measures and treatment recommendations. Conclusions: Axitinib is a drug that has been shown to increase PFS after 1st line progression, with a tolerable toxic profile. With the approval of nivolumab and cabozantinib, the place of Axitinib in sequential therapy is yet to be defined