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

J. G. Aerts*, H. Codrington, N. A. G. Lankheet, S. Burgers, B. Biesma, A. -M. C. Dingemans, A. D. Vincent, O. Dalesio, H. J. M. Groen, E. F. Smit

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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. 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). 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. PFS was not significantly different between the arms. OS was significantly improved in the combination arm, an effect restricted to NSQ histology. NCT00835471.
Original languageEnglish
Pages (from-to)2860-2865
JournalAnnals of Oncology
Issue number11
Publication statusPublished - Nov 2013


  • second line
  • intercalated
  • erlotinib

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