Lung cancer is the most commonly diagnosed cancer and accounts for 20% of cancer-related mortality worldwide.¹ An estimated 610 200 patients (22% of cancer-related mortality) died from lung cancer in 2015 in China.² Non–small cell lung cancer (NSCLC) comprises 80% to 85% of lung cancers, and most patients present with locally advanced or metastatic disease at time of diagnosis.³ Recent advancements in the understanding of NSCLC malignant neoplasm molecular pathways have led to the development of targeted therapeutics.^4-6 With the advent of novel treatments, such as targeted therapy, it is becoming increasingly common for patients to control their disease through multiple lines of therapy.

Anlotinib (AL3818) is a novel multitarget tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling. The objective of this study was to assess the safety and efficacy of third-line anlotinib for patients with refractory advanced non-small-cell lung cancer (RA-NSCLC). Eligible patients were randomised 1 : 1 to receive anlotinib (12 mg per day, per os; days 1–14; 21 days per cycle) or a placebo. The primary end point was progression-free survival (PFS). A total of 117 eligible patients enrolled from 13 clinical centres in China were analysed in the full analysis set. No patients received immune check-point inhibitors and epidermal growth factor receptor status was unknown in 60.7% of the population. PFS was better with anlotinib compared with the placebo (4.8 vs 1.2 months; hazard ratio (HR)=0.32; 95% confidence interval (CI), 0.20–0.51; P<0.0001), as well as overall response rate (ORR) (10.0%; 95% CI, 2.4–17.6% vs 0%; 95% CI, 0–6.27%; P=0.028). The median overall survival (OS) was 9.3 months (95% CI, 6.8–15.1) for the anlotinib group and 6.3 months (95% CI, 4.3–10.5) for the placebo group (HR=0.78; 95% CI, 0.51–1.18; P=0.2316). Adverse events were more frequent in the anlotinib than the placebo group. The percentage of grade 3–4 treatment-related adverse events was 21.67% in the anlotinib group. Anlotinib as a third-line treatment provided significant PFS benefits to patients with RA-NSCLC when compared with the placebo, and the toxicity profiles showed good tolerance.

To explore the optimal treatment strategy for patients who harbor sensitive EGFR mutations, a head‐to‐head study was performed to compare chemotherapy and gefitinib in combination or with either agent alone as first‐line therapy, in terms of efficacy and safety. A total of 121 untreated patients with advanced lung adenocarcinoma who harbored sensitive EGFR mutations were randomly assigned to receive gefitinib combined with pemetrexed and carboplatin, pemetrexed plus carboplatin or gefitinib alone. The progression‐free survival (PFS) of patients in the combination group (17.5 months, 95% CI, 15.3–19.7) was longer than that of patients in the chemotherapy group (5.7 months, 95% CI, 5.2–6.3) or gefitinib (11.9 months, 95% CI, 9.1–14.6) group. The (hazard ratios) HRs of PFS for the combination group vs. chemotherapy and gefitinib groups were 0.16 (95% CI, 0.09–0.29, p < 0.001) and 0.48 (95% CI, 0.29–0.78, p = 0.003), respectively. The overall response rate (ORR) in the combination therapy group, chemotherapy group and the gefitinib group was 82.5%, 32.5% and 65.9%, respectively. The combinational strategy resulted in longer overall survival (OS) than chemotherapy (HR = 0.46, p = 0.016) or gefitinib (HR = 0.36, p = 0.001) alone. Our finding suggested that treatment with pemetrexed plus carboplatin combined with gefitinib could provide better survival benefits for patients with lung adenocarcinoma harboring sensitive EGFR mutations.