Oncogenic mutations of KRAS define the largest genomic subset of NSCLC (Figure). This patient group appears to derive less clinical benefit from chemotherapy than the overall NSCLC population. There are currently no targeted treatments specifically for patients with KRAS-mutant tumours of the lung.

Rapid growth and early development of metastatic disease are characteristic of small-cell lung cancer (SCLC), which constitutes approximately 15 % of all lung cancer cases. In limited-stage disease, a cure is possible with chemoradiotherapy. However, 68 % of patients present with extensive-stage SCLC (ES-SCLC). Although high initial responses to platinum-based chemotherapy and radiotherapy are observed, recurrence of chemo-refractory disease takes place as a rule.

As well as ALK fusion mutations and EGFR mutations, studies of the genetic profiles of patients with NSCLC have identified other mutations that might be used for additional targeted therapies. Among these, ROS1 and RET rearrangements both occur in 1 % to 2 % of patients with NSCLC. Crizotinib is known to target not only ALK, but also ROS1, among others. Patients with ROS1-positive advanced NSCLC are being treated with crizotinib 250 mg twice daily in the ongoing phase I, open-label, PROFILE 1001 study.

Approximately 11 % of Caucasian patients with NSCLC have tumours that harbour EGFR mutations, which occur in exons 18, 19, 20 and 21 of the EGFR gene. Common mutations include exon 19 in-frame deletions and the exon 21 Leu858Arg point mutation (L858R). Exon 20 insertions are known to mediate resistance [3]. Little data are available for the other more uncommon mutations.

How important is anti-angiogenesis in the treatment concept of lung cancer?

ALK fusion-gene–positive lung cancer occurs in approximately 5 % of patients with advanced NSCLC [1]. The ALK inhibitor crizotinib demonstrates significant initial efficacy in patients with ALK-positive advanced NSCLC.  However, most patients eventually develop resistance, with the central nervous system (CNS) being one of the most common sites of first progression.

The anti–PD-1 antibody pembrolizumab has been approved for treatment of patients with PD-L1–expressing, advanced NSCLC. The KEYNOTE-024 study focused on the first-line comparison of pembrolizumab with platinum-doublet chemotherapy. Chemotherapy regimens comprised five options, two of which (pemetrexed plus carboplatin; pemetrexed plus cisplatin) were used with non-squamous non-small–cell lung cancer (NSCLC) only.

According to an estimate by the World Health Organization, 1.37 million people worldwide die of lung cancer every year. Both incidence and lung-cancer–related mortality are substantial: to date, primary lung cancer remains the most common malignancy after nonmelanocytic skin cancer, and the global numbers of patients dying from it exceed those linked to any other malignancy.