Second-line therapies for relapsed small cell lung cancer (SCLC) patients remain a challenge, with limited clinical benefit because of rapid tumor growth, early dissemination and the development of drug resistance during the disease. Recent developments in genomic sequencing have provided further insight into the biology of the disease, identifying new targets and new pathways. Areas covered: This review details chemotherapy, targeted therapies and immune-checkpoint blockades that have been investigated as second-line treatments for SCLC patients using a PubMed search (period 1990 - 2016, terms used: SCLC, treatments, second line, therapy). Expert commentary: Recent genomic, proteomic and preclinical studies have identified novel therapeutic strategies currently being evaluated in clinical trials. Promising approaches for SCLC management include delta-like ligand-3 (DLL3)-targeted antibody-drug conjugate, combination targeted therapies, or targeted therapy-chemotherapy with an additive effect superior to the efficacy of single agents. The blockade of immune checkpoints has yielded promising preliminary results and is being investigated in ongoing trials. The inclusion of SCLC patients relapsing after platin-doublet induction in well-designed clinical trials remains a major challenge.
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