Complex Decisions for First-Line and Maintenance Treatment of Advanced Wild-Type Non-Small Cell Lung Cancer

Abstract

Until recently, the first-line treatment of advanced non-small cell lung cancer (NSCLC) required minimal clinical decision making. Patients who were eligible for chemotherapy received a platinum-based doublet, and 5-year survival rates were poor. With the advent of molecularly targeted agents and better tolerated chemotherapies-namely, bevacizumab, erlotinib, and pemetrexed-new therapeutic opportunities have emerged. Some of the strategies that have proven to be successful for the treatment of patients with NSCLC are targeting of the vascular endothelial growth factor, use of maintenance chemotherapy for patients without progression of disease after initial therapy, and tailoring of cytotoxic agents specific to the histology of an individual patient's cancer. Each approach has been independently shown to improve overall survival, but integrating the data from a number of complicated trialsintothe"best"approach for patients remains challenging. This review attempts to address three fundamental questions clinicians face in choosing first-line and maintenance treatment for advanced NSCLC, particularly nonsquamous histology: Is pemetrexed or a taxane agent better for combination with platinum therapy? Should bevacizumab be used, and is it beneficial when added to pemetrexed chemotherapy? When is maintenance therapy indicated, and which agent is best? The Oncologist 2015;20:299-306

Predictive biomarkers of response to PD-1/PD-L1 immune checkpoint inhibitors in non–small cell lung cancer

“…However, standard platinum doublet therapy seems to have reached a plateau in terms of efficacy [1,2]. The development of agents targeting vascular endothelial growth factor, use of histology to guide chemotherapy decisions, and addition of maintenance therapy have led to improvements of several months in overall survival (OS) over platinum doublet therapy alone, particularly for non-squamous NSCLC [3]. To extend survival further, novel types of drugs that target specific molecular pathways have been developed over the past decade [4].…”

Functional Analyses of Mutations in Receptor Tyrosine Kinase Genes in Non–Small Cell Lung Cancer: Double-Edged Sword of DDR2

“…More than 80% of lung cancers are non-small cell lung cancer (NSCLC), which includes adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Among patients with advanced NSCLC, cytotoxic chemotherapy has a response rate of 20% to 35% and a median survival period of 10 to 12 months (2). Meanwhile, several oncogenic driver mutations have been recognized in NSCLC, including genes encoding EGFR and ALK.…”

Platinum Complexes with Edda (Ethylenediamine -N, N - Diacetate) Ligands as Potential Anticancer Agents

“…It has therefore been necessary to synthesize more selective and less reactive molecule. This led to platinum complexes of the second and third generation (28)(29)(30). Complexes of the second generation are structural analogs of cisplatin, designed to overcome the toxicity of cisplatin, while the third generation complexes were created as even more advanced analogues with the main task to act on tumor cells resistant to cisplatin.…”