A randomized phase II study comparing erlotinib versus erlotinib with alternating chemotherapy in relapsed non-small-cell lung cancer patients: the NVALT-10 study

Ann Oncol. 2013 Nov;24(11):2860-5. doi: 10.1093/annonc/mdt341. Epub 2013 Aug 28.


Background: Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) administered concurrently with chemotherapy did not improve outcome in non-small-cell lung cancer (NSCLC). However, in preclinical models and early phase noncomparative studies, pharmacodynamic separation of chemotherapy and TKIs did show a synergistic effect.

Patients and methods: A randomized phase II study was carried out in patients with advanced NSCLC who had progressed on or following first-line chemotherapy. Erlotinib 150 mg daily (monotherapy) or erlotinib 150 mg during 15 days intercalated with four 21-day cycles docetaxel for squamous (SQ) or pemetrexed for nonsquamous (NSQ) patients was administered (combination therapy). After completion of chemotherapy, erlotinib was continued daily. Primary end point was progression-free survival (PFS).

Results: Two hundred and thirty-one patients were randomized, 115 in the monotherapy arm and 116 in the combination arm. The adjusted hazard ratio for PFS was 0.76 [95% confidence interval (CI) 0.58-1.02; P = 0.06], for overall survival (OS) 0.67 (95% CI 0.49-0.91; P = 0.01) favoring the combination arm. This improvement was primarily observed in NSQ subgroup. Common Toxicity Criteria grade 3+ toxic effect occurred in 20% versus 56%, rash in 7% versus 15% and febrile neutropenia in 0% versus 6% in monotherapy and combination therapy, respectively.

Conclusions: PFS was not significantly different between the arms. OS was significantly improved in the combination arm, an effect restricted to NSQ histology.

Study registration number: NCT00835471.

Keywords: NSCLC; erlotinib; intercalated; second line.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Disease-Free Survival
  • Docetaxel
  • Erlotinib Hydrochloride
  • Female
  • Glutamates / administration & dosage
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pemetrexed
  • Quinazolines / administration & dosage*
  • Recurrence
  • Taxoids / administration & dosage


  • Glutamates
  • Quinazolines
  • Taxoids
  • Pemetrexed
  • Docetaxel
  • Guanine
  • Erlotinib Hydrochloride

Associated data

  • ClinicalTrials.gov/NCT00835471