Nivolumab for advanced squamous cell lung cancer: what are the next steps?

Abstract

Lung cancer treatment is entering a new era. Non-small-cell lung cancer represents 85% of all lung cancers and can be classified in two histological subgroups: squamous cell and non-squamous cell lung cancer. 1 de Mello RA Madureira P Carvalho LS Araújo A O'Brien M Popat S EGFR and KRAS mutations, and ALK fusions: current developments and personalized therapies for patients with advanced non-small-cell lung cancer. Pharmacogenomics. 2013; 14: 1765-1777 Crossref PubMed Scopus (33) Google Scholar Several advances in the treatment of this aggressive disease have been made over the past decade. In 2005, Shepherd and colleagues 2 Shepherd FA Rodrigues Pereira J Ciuleanu T et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005; 353: 123-132 Crossref PubMed Scopus (5039) Google Scholar reported the primary role of targeting EGFR with tyrosine kinase inhibitors in the management of non-squamous cell lung cancer. Overall survival for patients with non-small-cell lung cancer who have EGFR mutations in exons 19 and 21 greatly improved with the development of treatments such as gefitinib and erlotinib, which have few toxic effects and easy oral administration. 1 de Mello RA Madureira P Carvalho LS Araújo A O'Brien M Popat S EGFR and KRAS mutations, and ALK fusions: current developments and personalized therapies for patients with advanced non-small-cell lung cancer. Pharmacogenomics. 2013; 14: 1765-1777 Crossref PubMed Scopus (33) Google Scholar , 2 Shepherd FA Rodrigues Pereira J Ciuleanu T et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005; 353: 123-132 Crossref PubMed Scopus (5039) Google Scholar Thereafter, the ALK-EML4 molecular pathway was found to have a primary role in patients harbouring ALK-EML4 fusions (roughly 5% of patients with non-small-cell lung cancer). First-line treatment with crizotinib, which targets this pathway, was shown to result in a median progression-free survival of 10·9 months and 74% of patients had an overall response. 3 Solomon BJ Mok T Kim DW et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014; 371: 2167-2177 Crossref PubMed Scopus (2319) Google Scholar Thr790Met EGFR mutations and MET amplification are the primary mechanisms of resistance to these treatments. 1 de Mello RA Madureira P Carvalho LS Araújo A O'Brien M Popat S EGFR and KRAS mutations, and ALK fusions: current developments and personalized therapies for patients with advanced non-small-cell lung cancer. Pharmacogenomics. 2013; 14: 1765-1777 Crossref PubMed Scopus (33) Google Scholar , 4 Agwa ES Ma PC Targeting the MET receptor tyrosine kinase in non-small cell lung cancer: emerging role of tivantinib. Cancer Manag Res. 2014; 6: 397 PubMed Google Scholar Several drugs and drug combinations, such as afatinib and tivantinib plus erlotinib, 5 Scagliotti GV Novello S Schiller JH et al. Rationale and design of MARQUEE: a phase III, randomized, double-blind study of tivantinib plus erlotinib versus placebo plus erlotinib in previously treated patients with locally advanced or metastatic, nonsquamous, non small-cell lung cancer. Clin Lung Cancer. 2012; 13: 391-395 Summary Full Text Full Text PDF PubMed Scopus (124) Google Scholar have been subsequently tested for their ability to overcome these resistance mechanisms. 1 de Mello RA Madureira P Carvalho LS Araújo A O'Brien M Popat S EGFR and KRAS mutations, and ALK fusions: current developments and personalized therapies for patients with advanced non-small-cell lung cancer. Pharmacogenomics. 2013; 14: 1765-1777 Crossref PubMed Scopus (33) Google Scholar Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trialNivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment. Full-Text PDF