Axitinib after Sunitinib in Metastatic Renal Cancer: Preliminary Results from Italian “Real-World” SAX Study

Abstract

Axitinib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) after failure of prior treatment with Sunitinib or cytokine. The present study is an Italian Multi-Institutional Retrospective Analysis that evaluated the outcomes of Axitinib, in second-line treatment of mRCC. The medical records of 62 patients treated with Axitinib, were retrospectively reviewed. The Progression Free Survival (PFS), the Overall Survival (OS), the Objective Response Rate (ORR), the Disease Control Rate (DCR), and the safety profile of axitinib and sunitinib–axitinib sequence, were the primary endpoint. The mPFS was 5.83 months (95% CI 3.93–7.73 months). When patients was stratified by Heng score, mPFS was 5.73, 5.83, 10.03 months according to poor, intermediate, and favorable risk group, respectively. The mOS from the start of axitinib was 13.3 months (95% CI 8.6–17.9 months); the observed ORR and DCR were 25 and 71%, respectively. When stratified patients by subgroups defined by duration of prior therapy with Sunitinib (≤ vs. >median duration), there was a statistically significant difference in mPFS with 8.9 (95% CI 4.39–13.40 months) vs. 5.46 months (95% CI 4.04–6.88 months) for patients with a median duration of Sunitinib >13.2 months. DCR and ORR to previous Sunitinib treatment was associated with longer statistically mPFS, 7.23 (95% CI 3.95–10.51 months, p = 0.01) and 8.67 (95% CI 4.0–13.33 months, p = 0.008) vs. 2.97 (95% CI 0.65–5.27 months, p = 0.01) and 2.97 months (95% CI 0.66–5.28 months, p = 0.01), respectively. Overall Axitinib at standard schedule of 5 mg bid, was well-tolerated. The most common adverse events of all grades were fatig (25.6%), hypertension (22.6%), gastro-intestinal disorders (25.9%), and hypothyroidism (16.1%). The sequence Sunitinib–Axitinib was well-tolerated without worsening in side effects, with a median OS of 34.7 months (95% CI 18.4–51.0 months). Our results are consistent with the available literature; this retrospective analysis confirms that Axitinib is effective and safe in routine clinical practice.

Survival Benefits of Second-line Axitinib Versus Everolimus After First Line Sunitinib Treatment in Metastatic Renal Cell Carcinoma

“…Previous real-world studies comparing the effectiveness of second-line targeted therapies for mRCC used different designs and reported heterogeneous results, with no convincing evidence of a difference in effectiveness between mTORi and VEGF TKI in the second-line setting [37]. Our results build on the existing real-world evidence which supports the benefits of second-line axitinib treatment over everolimus after prior anti-VEGF therapy [38][39][40] in patients showing longer DFT on first-line sunitinib treatment.…”

Second line therapy with axitinib after only prior sunitinib in metastatic renal cell cancer: Italian multicenter real world SAX study final results

“…To date there are no head-to-head studies or randomized clinical trials, that provide conclusive information about the best second-line. Several ‘real world’ studies confirmed the efficacy and safety of Axitinb in a not selected population [12–24].…”

Biomarkers of Prognosis and Efficacy of Anti-angiogenic Therapy in Metastatic Clear Cell Renal Cancer

“…Patients enrolled in the AXIS trial who reported a diastolic blood pressure ≥90 mmHg within the first 8 or 12 weeks of randomization had a longer survival independently on the treatment arm: 20.7 months (95% CI 18.4-24.6) vs. 12.9 months (95% CI 10.1-20.4) in the axitinib group (p = 0.01), and 20.2 months (95% CI 17.1-32.0) vs. 14.8 months (95% CI 12.0-17.7) in the sorafenib group (p = 0.002) (77). These findings could not be confirmed by the Italian SAX study on real-world use of axitinib (120). A recent retrospective study showed that grade 3 hypertension affected positively OS in patients treated with pazopanib in real-world settings (HR=0.22, 95% CI 0.05-0.8, p = 0.03) (121).…”