PURPOSE: The phase III CheckMate 722 trial (ClinicalTrials.gov identifier: NCT02864251 ) evaluated nivolumab plus chemotherapy versus chemotherapy in patients with epidermal growth factor receptor ( EGFR)–mutated metastatic non–small-cell lung cancer (NSCLC) after disease progression on EGFR tyrosine kinase inhibitors (TKIs). METHODS: Patients with disease progression after first- or second-generation EGFR TKI therapy (without EGFR T790M mutation) or osimertinib (with/without T790M mutation) were randomly assigned 1:1 to nivolumab (360 mg once every 3 weeks) plus platinum-doublet chemotherapy (once every 3 weeks) or platinum-doublet chemotherapy alone (once every 3 weeks) for four cycles. Primary end point was progression-free survival (PFS). Secondary end points included 9- and 12-month PFS rates, overall survival (OS), objective response rate (ORR), and duration of response (DOR). RESULTS: Overall, 294 patients were randomly assigned. At final analysis (median follow-up, 38.1 months), PFS was not significantly improved with nivolumab plus chemotherapy versus chemotherapy (median, 5.6 v 5.4 months; hazard ratio [HR], 0.75 [95% CI, 0.56 to 1.00]; P = .0528), with 9- and 12-month PFS rates of 25.9% versus 19.8%, and 21.2% versus 15.9%, respectively. Post hoc PFS subgroup analyses showed a trend favoring nivolumab plus chemotherapy in patients with tumors harboring sensitizing EGFR mutations (HR, 0.72 [95% CI, 0.54 to 0.97]), one line of previous EGFR TKI (0.72 [95% CI, 0.54 to 0.97]), or both (0.64 [95% CI, 0.47 to 0.88]). Median OS was 19.4 months with nivolumab plus chemotherapy versus 15.9 months with chemotherapy, while ORR was 31.3% versus 26.7%, and median DOR was 6.7 versus 5.6 months, respectively. Grade 3/4 treatment-related adverse events occurred in 44.7% and 29.4% of patients treated with nivolumab plus chemotherapy and chemotherapy alone, respectively. CONCLUSION: Nivolumab plus chemotherapy did not significantly improve PFS versus chemotherapy in patients with EGFR-mutated metastatic NSCLC previously treated with EGFR TKIs. No new safety signals were identified.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide and has a poor prognosis. Current treatments for advanced NSCLC included traditional chemotherapy, radiotherapy, targeted therapy, and immunotherapy. The efficacy of targeted therapy relies on oncogene addiction. Mesenchymal-epithelial transition factor (MET) gene can encode unconventional receptor tyrosine kinases with pleiotropic functions, when signals are abnormally activated, it can initiate and maintain tumor transformation, promote cell proliferation, survival, tumor invasion and angiogenesis. Thus, it is a promising therapeutic target. Previous studies have shown that elevated levels of HGF and/or overexpression of c-Met are associated with poor prognosis in lung cancer. In preclinical and clinical trials, c-MET inhibitors have shown some antitumor activity in NSCLC. Although the efficacy results of MET inhibitors in Phase III clinical trials are disappointing, given the molecular heterogeneity of NSCLC, only subgroups of patients with MET gene alterations may benefit from c-MET inhibitors. The challenge for the future is to screen out the potential beneficiaries. To solve this problem, there is need for large data analysis for the detection methods and treatment effects, to establish standards that meet the MET activation status, and determine reliable thresholds to achieve effective patient stratification and clinical decision making. This article summarized the structure of the hepatocyte growth factor (HGF)/c-Met axis, the different mechanisms of MET addiction, as well as MET amplification as acquired resistance mechanism to epidermal growth factor receptor-tyrosine kinase inhibitors, the latest advances of MET inhibitors, and immuotherapy in the treatment of NSCLC with MET alterations.

Background: Epidermal growth factor receptor (EGFR) mutations play essential roles in the treatment of non-small cell lung cancer (NSCLC) patients using EGFR tyrosine kinase inhibitors. Detection of EGFR mutations in blood cell-free DNA (cfDNA) seems promising. However, the mutation status in the plasma/serum is not always consistent with that in the tissues. Objectives: The aims of this study were to compare the mutation statuses in plasma to those in tissues and thus to determine the specific subgroups of NSCLC patients who may be the best candidates for EGFR mutation analyses using blood cfDNA. Methods: A total of 111 pairs of tissue and plasma samples were collected. Mutant-enriched PCR and sequencing analyses were performed to detect EGFR exon 19 deletions and exon 21 L858R mutations. Results: Mutations were discovered in 43.2% (48/111) of the patients. The overall rate of consistency of the EGFR mutation statuses for the 111 paired plasma and tissue samples was 71.2% (79/111). The sensitivity and specificity rates of detecting EGFR mutations in the plasma were 35.6% (16/45) and 95.5% (63/66), respectively. The disease stage and tumor differentiation subgroups showed significantly different detection sensitivities; the sensitivity was 10% in early-stage patients and 56% in advanced-stage patients (p = 0.0014). For patients with poorly differentiated tumors, the sensitivity was 77.8%, which was significantly different from those with highly differentiated (20%; p = 0.0230) and moderately differentiated tumors (19%; p = 0.0042). Conclusion: Blood analyses for EGFR mutations may be effectively used in advanced-stage patients or patients with poorly differentiated tumors.

Immune checkpoint inhibitors (ICIs) have heralded the advent of a new era in oncology by holding the promise of prolonged survival in severe and otherwise treatment-refractory advanced cancers. However, the remarkable antitumor efficacy of these agents is overshadowed by their potential for inducing autoimmune toxic effects, collectively termed immune-related adverse events (irAEs). These autoimmune adverse effects are often difficult to predict, possibly permanent, and occasionally fatal. Hence, the identification of risk factors for irAEs is urgently needed to allow for prompt therapeutic intervention. This review discusses the potential mechanisms through which irAEs arise and summarizes the existing evidence regarding risk factors associated with the occurrence of irAEs. In particular, we examined available data regarding the effect of a series of clinicopathological and demographic factors on the risk of irAEs.

Background and objective: This study investigated whether circulating tumour cells (CTC) are detectable in patients with non‐small cell lung cancer (NSCLC) and whether CTC count could provide prognostic information or serve as an indicator of patient response to chemotherapy.Methods: We enrolled 46 patients with newly diagnosed or recurrent NSCLC. CTC were measured at baseline in all patients and in 23 patients, CTC were also measured before every chemotherapy cycle. The relationship between CTC count and tumour size was analysed.Results: CTC were present in 40 patients (87%); among them, 29 (63%) had a CTC count of ≥3 cells/3.2 mL, 17 (37%) had a CTC count of ≥5 cells/3.2 mL and 7 (15.2%) had a CTC count of ≥8 cells/3.2 mL. The median progression‐free survival (PFS) and overall survival (OS) were 7.3 months and 16 months, respectively. A CTC count of more than eight prior to chemotherapy was a strong predictor of reduced PFS (P = 0.018) and OS (P = 0.026). A multivariate analysis indicated that baseline CTC count was an independent negative prognostic factor for survival. However, no correlation was observed between CTC count and tumour size after two chemotherapy cycles, its relationship with chemotherapy response still needs to be defined.Conclusion: Baseline CTC count is an independent negative prognostic factor for NSCLC; The relationship of CTC and survival after chemotherapy still needs to be defined.