New options for combination therapy for advanced non-squamous NSCLC.

Introduction: Nonsquamous non-small-cell lung cancer (NSCLC) is divided in oncogene-addicted subgroups, highly expressed programmed death ligand-1 (PD-L1 ≥ 50%) subgroup, and 'negative' subgroup. The latter represents the most common group comprising about 50% of all new diagnoses of nonsquamous NSCLC. For this group, chemotherapy was the standard approach with pemetrexed- and/or bevacizumab-based regimens reaching an overall survival of about 12-17 months. Areas covered: This review will focus on the new options for combination therapies, which have already recently arrived or are going to arrive in the clinical practice, mainly through registrative trials, for the management of advanced nonsquamous non oncogene-addicted NSCLC. A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question was undertaken in order to discuss this topic. Expert opinion: In the 'negative' nonsquamous NSCLC patients, first-line combinations of pembrolizumab, an anti-PD-1, or atezolizumab, an anti-PD-L1, plus chemotherapy are already available in the clinical practice, regardless of PD-L1 expression. In this group of patients, the combinations of antiangiogenic agents, such as ramucirumab and nintedanib, in combination with docetaxel, become new options for second-line treatment. More studies are needed to investigate new combinations for the treatment of these patients.