Pazopanib in Metastatic Renal Cancer: A “Real-World” Experience at National Cancer Institute “Fondazione G. Pascale”

Abstract

Pazopanib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma. The present study analyzed the outcomes of pazopanib in first-line treatment of mRCC, in a single Italian cancer center. In the light of the retrospective, observational nature and the unselected population, our experience can be defined a “real-world” study. The medical records of 38 mRCC patients treated with front-line pazopanib were retrospectively reviewed and analyzed. The progression free survival (PFS) and the overall survival (OS) were the primary endpoints, while secondary objectives included objective response rate (ORR), disease control rate (DCR), and treatment tolerability. Pazopanib achieved a median PFS (mPFS) of 12.7 months (95% CI, 6.9–18.5 months). The median OS (mOS) was 26.2 months (95% CI, 12.6–39.9 months); the observed ORR and DCR were 30.3 and 72.7%, respectively, with a median duration of response of 11 weeks. mPFS appeared not to be influenced by number of co-morbidities (< 3 vs. ≥3), gender, Fuhrman grade and age. Conversely, the ORR and the DCR positively affect the mPFS (HR = 0.05 [95% CI, 0.05–0.55], p = 0.01; HR = 0.10 [95% CI, 0.02–0.43], p = 0.002, respectively). A worse outcome was associated with a lower mPFS in patients with liver metastases (p = 0.2) and with a high tumor burden (number of metastatic sites < 6 vs. ≥6) (p = 0.08). Worst OS was observed in patients aged ≥70 years old (HR = 6.91 [95% CI, 1.49–31.91], p = 0.01). The treatment was well-tolerated: no grade 4 adverse events, nor discontinuation due to toxicities was reported. Grade 3 hypertension affected positively the OS reaching the statistical significance (HR = 0.22 [95% CI, 0.05–0.8], p = 0.03). Thyroid dysfunction (hypo and hyperthyroidism) seems to correlate with better outcome in terms of a longer mPFS (HR = 0.12 [95% CI, 0.02–0.78], p = 0.02). Our results are consistent with those reported in prospective phase III trials and the published retrospective “real world” experiences. This analysis confirms the safety and efficacy of pazopanib in first-line setting, both in frail patients with multiple co-morbidities and Karnofsky PS < 80% and in younger, healthier patients with a number of metastatic sites < 6.

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

“…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).…”

“…Furthermore, one meta-analysis including 11 retrospective and prospective studies enrolling mRCC patients receiving sunitinib or sorafenib failed to identify any predictive value of hypothyroidism (HR for progression=0.82, 95% CI 0.59-1.13, p = 0.22; 6 studies, 250 patients) (132). Thyroid dysfunction (both hypo and hyperthyroidism) may be associated with a longer PFS (HR=0.12, 95% CI 0.02-0.78, p = 0.02) in patients treated with pazopanib (121).…”

Pazopanib as first-line therapy for patients with metastatic kidney cancer

“…Профиль нежелательных явлений у пациентов, полу-чавших пазопаниб в качестве терапии первой линии при метастатическом ПКР, в рутинной клинической практике в целом соответствует результатам исследова-ний III фазы [19][20][21][22][23][24][25][26]. Так, диарея описывается в 16-52% наблюдений, артериальная гипертензия в 24-49%, тош-нота/рвота в 24-44%, анорексия/потеря массы тела в 7-27% и усталость в 11-58%.…”

“…Так, диарея описывается в 16-52% наблюдений, артериальная гипертензия в 24-49%, тош-нота/рвота в 24-44%, анорексия/потеря массы тела в 7-27% и усталость в 11-58%. Эти реакции наиболее часты и описаны целым рядом исследователей (n = 38-278) [19][20][21][22][23][24]26].…”

“…Аномальные тесты функции печени (например, повы-шение AЛT, AСT или билирубина) имели место у 13-36% пациентов; 3-4-я степень токсичности -у ≤15,7% паци-ентов [19][20][21][25][26]. Частота отмены препарата из-за побочных эффектов в разных исследованиях варьирова-ла от 6 до 15% [19][20][21][22]24].…”