Modeling tumor growth kinetics after treatment with pazopanib or placebo in
patients with renal cell carcinoma.
Author(s): Bonate PL(1), Suttle AB.
Affiliation(s): Author information:
(1)Astellas Pharma Global Development, Northbrook, IL 60062, USA.
peter.bonate@astellas.com
Publication date & source: 2013, Cancer Chemother Pharmacol. , 72(1):231-40
PURPOSE: The purpose of this study is to characterize tumor growth kinetics in
patients with renal cell carcinoma (RCC) after treatment with pazopanib or
placebo and to identify predictive patient-specific covariates.
METHODS: Different tumor growth models that included patient-specific covariates
were fit to tumor growth data from Phase 2 (n = 220) and Phase 3 (n = 423)
clinical trials using nonlinear mixed-effects modeling. Logistic regression was
used to determine whether individual model parameters or covariates were related
to occurrence of new lesions.
RESULTS: A modified Wang model that included a quadratic growth term and a
mixture model adequately described the data. Patients in Group 1 (93 %) showed
treatment-dependent tumor shrinkage followed by treatment-independent regrowth.
Patients in Group 2 (7 %) showed treatment-independent tumor shrinkage that did
not regrow. In Group 1, pazopanib 800 mg increased the tumor shrinkage rate by
267 % compared to placebo. Baseline tumor size was dependent on baseline
hemoglobin, baseline lactate dehydrogenase, study, and prior nephrectomy.
Logistic regression analysis showed that prior radiotherapy, baseline tumor size,
tumor shrinkage rate, tumor regrowth rate, study, and treatment (P < 0.01 for
all) were all important predictors of new lesions. Patients treated with placebo
were approximately twice as likely to develop new lesions than patients treated
with pazopanib.
CONCLUSIONS: Mathematical modeling of tumor growth kinetics can quantify the
effect of anticancer therapies. Pazopanib 800 mg was shown to be an effective
treatment for RCC that increased the tumor shrinkage rate by 267 % compared with
placebo and reduced the likelihood of developing new lesions.
|