Sunitinib malate in previously untreated, nonsquamous, non-small cell lung cancer patients over the age of 70 years: results of a Phase II trial

Invest New Drugs. 2013 Oct;31(5):1330-8. doi: 10.1007/s10637-013-9985-0. Epub 2013 Jun 13.

Abstract

Background: Some elderly patients may have reduced tolerance the standard therapy (chemotherapy doublets) for stage III/IV non-small cell lung cancer (NSCLC). Sunitinib malate (S), an oral, multitargeted kinase inhibitor, shows promise as 2nd-line NSCLC treatment. This study explored the safety/efficacy of S in elderly patients with previously untreated NSCLC.

Primary objective: disease control rate (DCR) at six-weeks.

Secondary objectives: overall response (OR, CR+PR), progression-free survival (PFS), time to progression (TTP), one-yr survival, quality of life (QOL), and safety.

Treatment: S 37.5 mg daily/42-day cycle until PD or intolerable toxicity. Key inclusion: chemo-naïve stage IIIB/IV NSCLC (nonsquamous histology); ECOG PS=0-1; ≥ 70 years; normal organ function. Exclusion: hemoptysis, anticoagulation, or clotting diathesis. Other standard S-specific criteria applied.

Results: 63 patients enrolled/60 treated.

Demographics: 51 % male, 95 % white, median age 78 years (range, 70-88), 73 % ECOG=1, 97 % Stage IV, 83 % adenocarcinoma, 44 % prior surgery, 19 % prior radiation. With a median of 2 cycles (range, 1-16), DCR=63 %, OR=7 % (0 CR, 4 PR). Median follow-up=5.8 months (all; 15.9 months survivors), median PFS =3.0 months (range, <1-25.1), median TTP=4.5 months (range, <1-25.1), and 1-year survival=26.4 % [95 % CI: 15.9, 38.2]. QOL declined initially, but improved over time. TREATMENT-related adverse events included: fatigue (48.3 %); diarrhea (38.3 %); thrombocytopenia (33.3 %), anorexia (26.7 %), mucositis (25.0 %); nausea (25.0 %), dysgeusia (20.0 %), and neutropenia (20.0 %). Conclusions The study met its primary endpoint. S produced acceptable DCR and QOL improved; however, OR was disappointing (7 %) and toxicity was greater than expected. A biomarker to identify patients more likely to benefit from S is needed.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Disease-Free Survival
  • Female
  • Humans
  • Indoles / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Male
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrroles / therapeutic use*
  • Quality of Life
  • Sunitinib
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Indoles
  • Protein Kinase Inhibitors
  • Pyrroles
  • Sunitinib