In a German Intergroup phase II study reported in the Journal of Clinical Oncology, Grünwald et al found that progression-free survival with first-line pazopanib was noninferior to doxorubicin in patients aged 60 years or older with inoperable metastatic soft-tissue sarcoma. Pazopanib was also associated with less grade 4 neutropenia.
Study Details
In the open-label trial, 120 patients (intent-to-treat [ITT] population; median age = 71 years) were randomly assigned 2:1 between October 2012 and March 2016 to receive pazopanib at 800 mg once daily until disease progression or intolerance (n = 81) or doxorubicin at 75 mg/m2 once every 3 weeks for up to six cycles (n = 39).
Noninferiority was assumed for progression-free survival if the upper limit of the 95% confidence interval (CI) for the hazard ratio (HR) was < 1.8 in the per-protocol population. Neutropenia and febrile neutropenia were key secondary endpoints.
Progression-Free Survival
The per-protocol population consisted of 74 patients in the pazopanib group and 32 in the doxorubicin group. Reasons for exclusion from per-protocol analysis consisted of withdrawal of consent, failure to start study treatment, and starting of another systemic therapy before progression.
Median follow-up was 11.8 months. Median progression-free survival was 4.4 months in the pazopanib group vs 5.3 months in the doxorubicin group; the hazard ratio on Cox regression analysis was 1.00 with a 95% confidence interval of 0.65–1.53, thus meeting the criterion for noninferiority of pazopanib. Progression-free survival rates were 53% vs 44% at 12 weeks (P = .298) and 26% vs 23% at 26 weeks (P = .738). Objective response rates were 12.3% vs 15.4%. In the ITT population, median overall survival was 12.3 months in the pazopanib group vs 14.3 months in the doxorubicin group (HR = 1.08, 95% CI = 0.68–1.72, P = .735).
Adverse Events
In the ITT population, laboratory or clinical grade 4 neutropenia occurred in 0% of the pazopanib group vs 56.4% of the doxorubicin group (P < .0001). Febrile neutropenia occurred in 0% vs 10.3% (P = .003).
Treatment-related adverse events of any grade that occurred in ≥ 10% of patients were diarrhea, hypertension, hypothyroidism, and general physical health deterioration in the pazopanib group, and alopecia, neutropenia, stomatitis, anemia, leukopenia, and mucosal inflammation in the doxorubicin group. Discontinuation of treatment due to toxicity occurred in 22.2% of the pazopanib group and 7.7% of the doxorubicin group. Treatment-related serious adverse events occurred in 33.3% of the pazopanib group vs 27.0% of the doxorubicin group (P = .4933).
The investigators concluded, “Pazopanib was noninferior to doxorubicin, rendering pazopanib a putative therapeutic option in the first-line treatment of [soft-tissue sarcoma] in patients age 60 years or older. The distinct adverse event profile may be used to counsel patients and tailor therapy to individual needs.”
Viktor Grünwald, MD, of the Clinic for Internal Medicine (Tumor Research) and Clinic for Urology, University Hospital Essen, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by a grant from GlaxoSmithKline, which was transitioned to Novartis during the study. For full disclosures of the study authors, visit ascopubs.org.
