Xingsheng Hu

Clinical significance of pretreatment plasma biomarkers in advanced non-small cell lung cancer patients.

BACKGROUND The use of biomarkers for selecting non-small cell lung cancer (NSCLC) patients for treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is essential. The aim of this study was to explore whether biomarkers detected in plasma were predictive for response to EGFR-TKIs and survival time of NSCLC patients. METHODS Tumor tissues and paired blood were collected from 134 advanced NSCLC patients treated with EGFR-TKIs. EGFR mutations in both types of specimens, and expression of transforming growth factor-alpha and beta one (TGF-α and TGF-β1) were assessed in NSCLC patients. Concentrations of circulating free DNA were detected in plasma from both NSCLC patients and healthy subjects. The clinical significance of EGFR mutations, levels of cytokines, and circulating free DNA was assessed in advanced NSCLC patients. RESULTS EGFR mutations were detected in 68 tumor samples and 17 plasma samples of 134 NSCLC patients. The concentrations of circulating free DNA were higher in NSCLC patients than in healthy subjects. Patients with high TGF-β1 level showed shorter overall survival and worse response to EGFR-TKIs than patients with low TGF-β1 level. CONCLUSIONS Plasma levels of TGF-β1 may be a marker for predicting response to EGFR-TKIs and survival time in NSCLC patients.

Cisplatin combined with irinotecan or etoposide for untreated extensive‐stage small cell lung cancer: A multicenter randomized controlled clinical trial

This study evaluated the efficacy and safety of irinotecan/cisplatin (IP) and etoposide/cisplatin (EP) in extensive‐stage small cell lung cancer (ES‐SCLC) and the distribution of uridine diphosphate glucuronosyltransferase (UGT1A1). The relationship between UGT1A1 genotypes and patient outcomes was also assessed.

Clinical characteristics and response to tyrosine kinase inhibitors of patients with non-small cell lung cancer harboring uncommon epidermal growth factor receptor mutations

Objective To investigate the clinical features of patients with non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor (EGFR) mutations, and the treatment outcomes of EGFR tyrosine kinase inhibitors (TKIs) in these patients. Methods We retrospectively analyzed the data of 128 NSCLC patients pathologically diagnosed with uncommon EGFR mutation in the Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and Beijing Hospital from January 2010 to December 2015, including 40 advanced patients who received EGFR-TKI. Results Among the total 128 patients, 11 patients were non-adenocarcinoma, including squamous carcinoma (3.9%), adenosquamous carcinoma (2.3%), large cell carcinoma (0.8%), and composite neuroendocrine carcinoma (1.6%). Single mutations accounted for 75.0% (96/128), including G719X (29.7%), S768I (18.0%), 20 exon insertion (13.3%), L861Q (12.5%),De novo T790M (0.8%), and T725 (0.8%). Thirty-two patients harbored complex mutations. Forty advanced patients received EGFR-TKI, the objective response rate (ORR) was 20.0%, the disease control rate (DCR) was 85.0%, and the progression-free survival (PFS) was 6.4 [95% confidence interval (95% CI), 4.8–7.9] months. The exploratory analysis of tumor response and PFS in 33 patients with G719X/S768I/L861Q subtypes showed that ORR was 21.2% (7/33), the DCR was 93.9% (31/33), and PFS was 7.6 (95% CI, 5.8–9.4) months. Patients with exon 20 insertion mutation andDe novo T790M experienced rapid disease progression with PFS no more than 2.7 months. Conclusions Uncommon EGFR-mutant NSCLCs are heterogeneous, EGFR-TKIs can have different efficacy in this specific subtype, and thus further individual assessment is required for each case.

A phase I trial of an oral subtype-selective histone deacetylase inhibitor, chidamide, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer

Objective This phase I study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase (HDAC) inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer (NSCLC). Methods Ten patients received oral chidamide 20, 25, or 30 mg twice per week continuously with paclitaxel (175 mg/m2) and carboplatin [area under the curve (AUC) 5 mg/mL/min] administered in a 3-week cycle. Patients with response and stable disease after four cycles maintained chidamide monotherapy until disease progression or unacceptable toxicity. Blood samples were collected for pharmacokinetic analysis after the first single oral of chidamide and first combination treatment in cycle 1 from all patients. Results Two dose-limiting toxicities were recorded in the 30 mg cohort, including thrombocytopenia and prolonged neutropenia in the first cycle. Grade 3/4 neutropenia in any cycle was observed in all patients, but was not associated with significant complications. Other grade 3/4 hematologic toxicities included thrombocytopenia and leucopenia. No significant changes were observed in pharmacokinetic parameters for both chidamide and paclitaxel. One patient in the 20 mg cohort had confirmed partial response (PR). Two out of 5 patients with brain metastases had intracranial complete remission after 4-cycle treatment. Conclusions Chidamide combined with paclitaxel and carboplatin was generally tolerated without unanticipated toxicities or clinically relevant pharmacokinetic interactions. The recommended dose for chidamide in this combination was established at 20 mg, and a phase II trial is ongoing with this regimen in patients with advanced NSCLC.

Survival of patients with advanced lung adenocarcinoma before and after approved use of gefitinib in China

To compare the overall survival (OS) of patients with advanced lung adenocarcinoma in China before and after the approved use of gefitinib, and analyze clinical factors that may affect OS.

Suitability of Surgical Tumor Tissues, Biopsy, or Cytology Samples for Epidermal Growth Factor Receptor Mutation Testing in Non–Small Cell Lung Carcinoma Based on Chinese Population

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation status is crucial in treatment selection for non–small cell lung cancer (NSCLC) patients; however, the detection materials’ availability remains challenging in clinical practice. In this study, we collected surgical resection tissues, lymph node biopsy, and cytological samples for EGFR mutation testing and investigated the associations between gene mutation and clinical characteristics. METHODS: Two hundred and seventy-six NSCLC adenocarcinoma specimens were collected, and highly sensitive amplification refractory mutation system method was implemented for EGFR mutation detection, with clinicopathologic characteristics involved in the final analysis. RESULTS: In the total of 276 samples, 96% (265/276) of tumors obtained evaluable EGFR mutation status, the frequency of mutation was 55.8% (148/265) in all specimens, and three different type samples shared a comparable successful testing rate: 97.4% (38/39) in surgical tumor tissues, 100% (108/108) in lymph node biopsy samples, and 92.2% (119/129) in cytological samples. EGFR mutation was significantly associated with sex, smoking history, lymph node metastasis status (N stage), primary tumor size, testing tissues origin, and sample type (P < .05). Multivariate analysis reconfirmed that smoking history and primary tumor size shared significant correlation with EGFR mutation after adjustment. CONCLUSIONS: Both lymph node biopsy and cytological samples were suitable surrogates for EGFR mutation detection in NSCLC compared with tumor tissues, gene status should be detected widely considering the high EGFR mutation rate, and nonsmoking history together with smaller primary tumor size was an independent indicator of EGFR mutation status.

Real world study of regimen containing bevacizumab as first-line therapy in Chinese patients with advanced non-small cell lung cancer: Bevacizumab as first-line for NSCLC

Large scale randomized controlled trials have demonstrated that the use of bevacizumab in addition to chemotherapy in patients with advanced non‐small cell lung cancer (NSCLC) conveys significant survival benefits. We explored the clinical impact of a first‐line regimen containing bevacizumab (B+) versus a non‐bevacizumab regimen (non‐B) in advanced non‐squamous NSCLC (NS‐NSCLC) patients in a real world setting.

Gemcitabine combined with cisplatin as adjuvant chemotherapy for non-small cell lung cancer: A retrospective analysis

This study was conducted to evaluate the value of gemcitabine combined with cisplatin as adjuvant chemotherapy for radical resection of non‐small cell lung cancer.

A Retrospective Study of the Efficacy and Toxicity of Irinotecan in Combination with Nedaplatin versus Irinotecan in Combination with Cisplatin as Salvage Treatment in Refractory or Relapsed Small Cell Lung Cancer

BACKGROUND AND OBJECTIVE At present no standard second-line combination has been established for recurrent small cell lung cancer (SCLC). Therefore we evaluate the efficacy and safety of irinotecan in combination with nedaplatin/cisplatin against refractory or relapsed small cell lung cancer. METHODS In this retrospective study, we analyzed the data of 1,140 patients who diagnosed small cell lung cancer at our hospital from April 2009 to April 2012. Of all the patients, 34 patients were treated with irinotecan and nedaplatin (irinotecan 60 mg/m2 on days 1, 8 nedaplatin 85 mg/m2 day 1, every 3 weeks) , and 20 patients were treated with irinotecan and cisplatin (irinotecan 60 mg/m2 on days 1, 8 cisplatin 75 mg/m2 day 1, every 3 weeks) as the second-line treatment. Prognostic factors of overall survival (OS) were estimated by Kaplan-Meier and Coxs Regression-proportional hazards model. RESULTS Of all the 54 eligible patients, median progression free survival (PFS) was 4.9 months, and median OS was 13.3 months. Median PFS was 5.4 months for irinotecan plus nedaplatin (IN) and 4.9 months for irinotecan plus cisplatin (IC), respectively (P=0.465). Median OS was 14.3 months and 13.3 months, respectively (P=0.704). In multivariate analysis, ECOG PS, number of metastases and cycles of chemotherapy were independent prognostic factors. The toxicities were mild, while toxicity profile was slightly different for each of the arms: hematologic toxicity was higher in IN group, and diarrhea was higher in IC group. CONCLUSIONS Irinotecan plus platinum is effective and tolerable for refractory and relapsed small cell lung cancer. Irinotecan plus nedaplatin is non-inferior to irinotecan plus cisplatin in terms of efficacy and safety.

Heterogeneity-based, multiple mechanisms in the resistance to osimertinib (AZD9291): A case report: Heterogeneity-induced resistance to osimertinib

Osimertinib is a novel, irreversible, mutant‐selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR mutations and the EGFR T790 mutation. Here, we report a woman with EGFR‐mutated lung adenocarcinoma who, after 23‐month treatment with gefitinib, developed the EGFR T790M mutation, which converted the T790M status from positive to negative before osimertinib treatment and developed MET amplification, leading to rapid progression on osimertinib in two months. Subsequent treatment with crizotinib and c‐Met inhibitor plus gefitinib also failed to improve the clinical outcome, suggesting the potential existence of another resistance mechanism. Our findings revealed the underlying multiple and heterogeneous mechanisms in resistance to osimertinib, suggesting combination strategies should be considered post‐osimertinib progression.