Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

Olivia Horga, Mercer University College of Pharmacy

It is reported that renal cell carcinoma (RCC) accounts for 2% to 3% of all malignant diseases in adults. It is also reported that despite the earlier detection, the rate of RCC-related mortality has increased, suggesting that recurrence and advanced disease are responsible for mortality. [1]

The American Cancer Society reports that targeted therapies for kidney cancer, including everolimus, are used to treat advanced kidney cancers after other drugs have been tried. [2]

According to the European Society for Medical Oncology guidelines, everolimus is used after first-line treatment with vascular endothelial growth factor receptor (VEGF) targeted therapy. [3]

The proposed mechanism of action for cabozantinib classifies it as a potent inhibitor of proinvasive receptor tyrosine kinases. It is suggested that cabozantinib induces apoptosis of cancer cells and suppresses tumor growth metastasis, and angiogenesis. [4]

Title: Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma [5]
Design Randomized, open-label, phase three trial; N = 658
Objective To evaluate the efficacy of cabozantinib as compared with everolimus in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy
Study Groups Patients with advanced or metastatic renal-cell carcinoma with a clear-cell component and measurable disease; cabozantinib group (n = 330); everolimus groups (n = 328); progression-free – survival population for the primary end-point analysis (n = 375)
Methods Patients received either cabozantinib 60 mg daily or everolimus 10 mg daily; treatment continued as long as clinical benefit was observed or until development of toxic effects
Duration Randomization to one of the treatment groups: August 2013 – November 2014; minimum follow-up for progression-free – survival population = 11 months; median duration of treatment: 7.6 months cabozantinib; 4.4 months everolimus
Primary Outcome Measure Duration of progression free survival
Baseline Characteristics Progression-free Survival Population
Characteristic Cabozantinib

(n = 187)

Everolimus

(n = 188)

Median age, years (range) 62 (36 – 83) 61 (31 – 84)
Male, n 142 130
Female, n 45 57
Geographic region
Europe, n 83 84
North America, n 76 64
Asia – Pacific, n 25 36
Latin America, n 3 4
Race
White, n 157 147
Asian, n 12 20
Black, n 4 2
Other, n 10 6
Not reported, n 4 12
Prior VEGFR tyrosine kinase inhibitors
1, n 137 136
≥ 2, n 50 52
Previous systemic therapy
Sunitinib, n 114 113
Pazopanib, n 87 78
Axitinib, n 28 28
Sorafenib, n 11 19
Bevacizumab, n 1 7
Interleukin-2, n 11 13
Interferon alfa, n 6 13
Nivolumab, n 9 11
Radiotherapy, n 56 61
Nephrectomy, n 156 153
Results Cabozantinib Everolimus
Median progression-free survival 7.4 months

(95% confidence interval [CI], 5.6 – 9.1)

3.8 months

(95% CI, 3.7 – 5.4)

Adverse Events Common Adverse Events (grade three or four): cabozantinib, n = 226 (68%); everolimus, n = 187 ( 58%)
Serious Adverse Events (grade five): cabozantinib, n = 22 (7%); everolimus, n = 25 (8%); treatment-related: cabozantinib, n = 1 (0.5%) [death]; everolimus, n = 2 (1.1%) [aspergillus infection and aspiration pneumonia]
Percentage that Discontinued due to Adverse Events: 9% of patients who received cabozantinib; 10% of patients who received everolimus
Study Author Conclusions Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.

The study suggests that patients who underwent treatment with cabozantinib had a longer progression-free survival than those treated with everolimus. The study also suggests that the death rate was 33% lower with cabozantinib than with everolimus. [5]

Considering that cabozantinib had greater efficacy in patients with RCC, patients who suffer from this malignancy may benefit from a course of therapy that includes cabozantinib.

References

  1. Cleveland Clinic. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/nephrology/renal-cell-carcinoma/. Accessed November 9, 2015.
  2. American Cancer Society. http://www.cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-adult-treating-targeted-therapy. Accessed November 9, 2015.
  3. European Society for Medical Oncology. http://www.esmo.org/Guidelines/Genitourinary-Cancers/Renal-Cell-Carcinoma. Accessed November 9, 2015.
  4. Cabozantinib [package insert]. San Francisco, CA: Exelixis, Inc.; 2012
  5. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373(19):1814-23.
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