title: Second-line combination therapies in nonsmall cell lung cancer without known driver mutations.
abstract: In advanced nonsmall cell lung cancer (NSCLC) patients, platinum-based combination chemotherapy is standard treatment in the first-line setting; however, the large majority of patients ultimately progress. For more than a decade, single-agent therapy with docetaxel, pemetrexed or erlotinib has been the standard of care after failure with platinum salts, showing some benefit over best supportive care. Nonetheless, prognosis remains poor and new second-line strategies are urgently needed. Combinations of cytotoxic agents, including rechallenge with platinum salts, do not offer clear benefit over single-agent therapy for the majority of patients. In patients without a known tumoural oncogenic driver mutation, regimens based on combinations of targeted agents have shown promising results; however, a clear role in therapeutic management is yet to be established. Some success has been reported in recent research combining a cytotoxic agent with targeted therapies.In this review, we summarise published data for the various strategies evaluated over the past decade in second-line treatment of NSCLC patients without a known driver mutation. We focus on combination treatments and consider future perspectives, including the need to identify predictive markers to support personalised therapeutic strategies.
authors.affiliation: Dept of Cancer Medicine, Gustave Roussy, Villejuif, France.
authors.forename: Maria-Virginia
authors.initials: MV
authors.lastname: Bluthgen
authors.affiliation: Dept of Cancer Medicine, Gustave Roussy, Villejuif, France benjamin.besse@gustaveroussy.fr.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D019233:Retreatment; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor