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Clinical Trial
. 2017 Jun 27;117(1):8-14.
doi: 10.1038/bjc.2017.137. Epub 2017 May 16.

Second-line pazopanib in patients with relapsed and refractory small-cell lung cancer: a multicentre phase II study of the Hellenic Oncology Research Group

F Koinis  1 , S Agelaki  1 , V Karavassilis  1 , N Kentepozidis  1 , E Samantas  1 , S Peroukidis  1 , P Katsaounis  1 , E Hartabilas  1 , I I Varthalitis  1 , I Messaritakis  1 , G Fountzilas  1 , V Georgoulias  1 , A Kotsakis  1
Affiliations
Clinical Trial

Second-line pazopanib in patients with relapsed and refractory small-cell lung cancer: a multicentre phase II study of the Hellenic Oncology Research Group

F Koinis et al. Br J Cancer. .

Abstract

Background: Pazopanib is a tyrosine kinase inhibitor with antiangiogenic activity. Vascular endothelial growth factor expression is increased in SCLC and is correlated with poor prognosis. The efficacy and tolerance of second-line pazopanib in SCLC was evaluated.

Patients and methods: Patients with platinum-sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were enrolled in a multicentre phase II study. The primary end point was the progression-free survival rate (PFS-R) at week 8 in each cohort. Pazopanib (800 mg per day per os) was administered until progressive disease (PD). Circulating tumour cells (CTCs) were enumerated using the Cellsearch assay.

Results: All patients were evaluable for response and toxicity. In the intention-to-treat analysis, eight (13.8%) patients achieved partial response (PR) (95% confidence interval (CI): 5.0-22.7), 20 (34.5%) stable disease (SD) and 30 (51.7%) PD. Accrual in cohort B was halted because the hard-stop rule was met; in cohort A, the PFS-R was 59% (95% CI: 43.5-74.4; PR=7, SD=16). Nine (23.1%) patients received pazopanib for >6 months and 3 of them for >12 months. One pazopanib cycle resulted to a significant decrease to the number of patients with ⩾5 CTCs/7.5 ml of blood (20%) compared with baseline (50%). The median PFS and OS for all patients was 2.5 months (95% CI: 1.9-3.1 months) and 6.0 months (95% CI: 3.8-8.2 months), respectively (cohort A: PFS=3.7 months and OS=8.0 months). No unexpected toxicity was observed.

Conclusions: Second-line treatment with pazopanib in platinum-sensitive SCLC is well tolerated and resulted in promising objective responses and disease control; CTC enumeration might serve as a reliable surrogate biomarker of response.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Survival curves of SCLC patients receiving pazopanib according to disease status. Kaplan–Meier curves for PFS (A) and OS (B) according to the platinum sensitivity.
Figure 2
Figure 2
Survival curves of SCLC patients receiving pazopanib according to baseline levels of CTC's. Kaplan–Meier curves for PFS (A) and OS (B) according to the number of CTCs/7.5 ml of blood at baseline.
See this image and copyright information in PMC

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