Pazopanib maintenance after first-line etoposide and platinum chemotherapy in patients with extensive disease small-cell lung cancer: a multicentre, randomised, placebo-controlled Phase II study (KCSG-LU12-07)

Br J Cancer. 2018 Mar 6;118(5):648-653. doi: 10.1038/bjc.2017.465. Epub 2018 Jan 30.

Abstract

Background: We investigated whether pazopanib maintenance following first-line chemotherapy would improve survival in patients with extensive disease small-cell lung cancer (ED-SCLC).

Methods: This study is a randomised, placebo-controlled, phase II study that enroled ED-SCLC patients who had not progressed after four cycles of etoposide plus platinum therapy. Eligible patients were randomly assigned (1 : 1 ratio) to either placebo or pazopanib 800 mg per day until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS).

Results: 97 patients were enroled and randomly assigned; 2 patients did not receive study drugs. In total, 95 patients received maintenance therapy (pazopanib, n=48; placebo, n=47) and were included in the analyses. Grade 3 toxicities for pazopanib maintenance were thrombocytopenia (10.4%, including one case with grade 4 toxicity), liver enzyme elevation (10.4%), fatigue (6.3%), and hypertension (6.3%). Median PFS was 3.7 months for pazopanib maintenance and 1.8 months for placebo (hazard ratio 0.44, 95% confidence interval: 0.29-0.69, P<0.0001).

Conclusions: Pazopanib maintenance significantly prolonged PFS in patients with ED-SCLC. Given the toxicity profiles, however, relevant biomarkers to select patients for benefit from pazopanib should be further investigated.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Double-Blind Method
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Etoposide / therapeutic use
  • Female
  • Humans
  • Indazoles
  • Lung Neoplasms / drug therapy*
  • Maintenance Chemotherapy / methods*
  • Male
  • Middle Aged
  • Platinum / administration & dosage
  • Platinum / therapeutic use
  • Progression-Free Survival
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Small Cell Lung Carcinoma / drug therapy*
  • Sulfonamides / administration & dosage*
  • Sulfonamides / adverse effects
  • Survival Analysis
  • Treatment Outcome

Substances

  • Indazoles
  • Pyrimidines
  • Sulfonamides
  • Platinum
  • Etoposide
  • pazopanib