Does Dose Modification Affect Efficacy of First-Line Pazopanib in Metastatic Renal Cell Carcinoma?

• Published in: Drugs in R&D Vol. 17; no. 3; pp. 461 - 467
• Main Authors: Grassi, Paolo, Verzoni, Elena, Ratta, Raffaele, Porcu, Luca, Prisciandaro, Michele, Mennitto, Alessia, Calareso, Giuseppina, de Braud, Filippo, Procopio, Giuseppe
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-09-2017; Springer Nature B.V
• Subjects: Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - therapeutic use; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Internal Medicine; Kidney cancer; Kidney Neoplasms - drug therapy; Kidney Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Neoplasm Metastasis; Original; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy; Proportional Hazards Models; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Retrospective Studies; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Targeted cancer therapy; Treatment Outcome
• ISSN: 1174-5886; 1179-6901
• DOI: 10.1007/s40268-017-0203-y

Background
Pazopanib is a standard treatment for metastatic renal cell carcinoma (mRCC), and 800 mg/daily is considered the optimal dose. However, some patients require dose modification because of toxicity. Whether a reduced dose of pazopanib is as effective as the standard dose in achieving clinical benefit remains unclear.
Objectives
Our objective was to conduct a retrospective analysis to investigate the clinical effect of different therapeutic doses of first-line pazopanib in patients with mRCC.
Methods
Consecutive patients with mRCC treated with first-line pazopanib between 2011 and 2016 at the Istituto Nazionale Tumori of Milan were retrospectively analysed for demographics, response, outcomes, and toxicity. Three patient groups were compared: group 1 received the standard dose of 800 mg/day; group 2 started with 800 mg/day and then reduced the dose to 400 or 600 mg/day because of toxicity; and group 3 received a reduced starting dose of 400 or 600 mg/day because they had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 and/or comorbidities.
Results
In total, 69 patients were evaluated: 34 in group 1, 19 in group 2, and 16 in group 3. After a median follow-up of 13.9 months (range 0.3–43.8), 27 (39.1%) patients had progressive disease (PD) and three (4.3%) patients had died. The incidence rate of PD or death per 100 person-months was 2.5 [95% confidence interval (CI) 0.6–4.4; hazard ratio (HR) 1] in group 1 and 3.9 (95% CI 0–14.3; HR 1.43) in the combined group (2 + 3). The discontinuation rate due to PD was 28% in group 1, 42% in group 2, and 44% in group 3. The objective response rate was 44, 11, and 19% in groups 1, 2, and 3, respectively.
Conclusions
Our results may suggest that patients with mRCC receiving a lower dose of first-line pazopanib might not have a meaningful progression-free survival advantage compared with those receiving a standard dose. These data highlight that proper management of treatment-related side effects may lead to optimal drug exposure.