M.J. Kim

The BIM Deletion Polymorphism and its Clinical Implication in Patients with EGFR-Mutant Non-Small-Cell Lung Cancer Treated with EGFR Tyrosine Kinase Inhibitors

Introduction: A germline BIM deletion polymorphism has been proposed to predict poor treatment response to certain kinase inhibitors. The purpose of this study was to explore whether the BIM deletion polymorphism predicts treatment efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in Korean patients with EGFR-mutant non–small-cell lung cancer (NSCLC). Methods: Peripheral blood samples from a total of 205 patients with EGFR-mutant NSCLC who were treated with EGFR TKIs between July 2008 and April 2013 were included. The incidence of BIM deletions in these samples was detected by polymerase chain reaction. We compared the clinical outcomes in patients with and without the polymorphism after treatment with EGFR TKIs (gefitinib or erlotinib). Results: The BIM deletion polymorphism was present in 15.6% (32 of 205) of patients. One patient was homozygous for the deletion, and the remaining 31 had heterozygous deletions. The majority of patients were younger than 65 years (74%), female (68%), never smokers (76%), and had stage IV NSCLC (67%). There were no associations between the BIM deletion polymorphism and clinicopathological features including gender, age, smoking status, histology, stage, and number of metastasis sites. Patients with and without the BIM deletion polymorphism had similar objective response rates (91 vs. 84%, p = 0.585). Progression-free survival and overall survival did not differ significantly between patients with and without the BIM deletion polymorphism (median progression-free survival 12 vs. 11 months, p = 0.160; median overall survival 31 vs. 30 months, p = 0.452). Multivariate analysis identified significantly predictive markers for clinical outcomes of EGFR TKIs including Eastern Cooperative Oncology Group performance status 0–1, adenocarcinoma histology, recurrent disease, and EGFR mutation type. The results were validated in an independent cohort of 69 NSCLC patients. Conclusions: It remains to be determined whether the BIM deletion polymorphism provides intrinsic resistance or decreased sensitivity to EGFR TKIs in EGFR-mutant NSCLC patients.

The Role of Plasma Chromogranin A as Assessment of Treatment Response in Non-functioning Gastroenteropancreatic Neuroendocrine Tumors

Purpose Chromogranin A (CgA) has been considered to be valuable not only in the diagnosis but also in monitoring the disease response to treatment. However, only a few studies have been published on this issue. We purposed to evaluate whether biochemical response using plasma CgA level is reliable in concordance with the clinical response of grade 1-3 nonfunctiong gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Materials and Methods Between March 2011 and September 2013, a total of 27 cases in 18 patients were analysed, clinically and radiologically while serial CgA tests were also conducted during treatment. Tumor responses were defined by both Response Evaluation Criteria in Solid Tumors (RECIST) criteria ver. 1.1 and biochemical criteria based on the CgA level. Results Among the 27 cases analysed, no difference in the basal CgA level was observed with regard to gender, primary tumor site, tumor grade (World Health Organization classification), liver metastasis, number of metastatic site, and line of chemotherapy. The overall response rate (RR) by RECIST criteria ver. 1.1 was six out of the 27 cases (22.2%) and eight out of the 27 cases (29.6%) for biochemical RR. The overall concordance rates of the response based on RECIST and biochemical criteria were 74%. In grades 1 and 2 GEP-NETs (n=17), the concordance rate of the disease control was 94.1%. There was a significant difference for progression-free survival (PFS) between responders and non-responder in accordance to biochemical criteria (35.73 months vs. 5.93 months, p=0.05). Conclusion This study revealed that changes of the plasma CgA levels were associated with tumour response. Additionally, biochemical response based on serial CgA may be a predictive marker for PFS in GEP-NETs.

Capecitabine in combination with either cisplatin or weekly paclitaxel as a first-line treatment for metastatic esophageal squamous cell carcinoma: a randomized phase II study

BackgroundThe aim of this study was to assess the efficacy and safety of a combination regimen of capecitabine plus cisplatin (CC) or capecitabine plus paclitaxel (CP) as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma.MethodsPatients with recurrent or metastatic esophageal squamous cell carcinoma were enrolled in this open-label, phase II, randomized trial. Patients were assigned to either the CC arm (days [D]1–14 capecitabine 1000xa0mg/m2 twice dailyu2009+u2009D1 cisplatin 75xa0mg/m2, every 3xa0weeks) or the CP arm (D1–14 capecitabine 1000xa0mg/m2 twice dailyu2009+u2009D1, 8 paclitaxel 80xa0mg/m2, every 3xa0weeks). The primary endpoint of the study was response rate and secondary endpoints were progression-free survival (PFS), overall survival (OS), toxicity and quality of life.ResultsA total of 94 patients were entered into this study between October 2008 and October 2012, 46 patients in the CC arm and 48 in the CP arm. Patients in both arms received a median of six cycles of treatment (range, 1–14) and the response rates were 57 and 58xa0% in the cisplatin and paclitaxel arm, respectively. With a median follow-up of 23xa0months, the median PFS was 5.1xa0months (95xa0% CI 4.0–6.2xa0months) in the cisplatin arm and 6.7xa0months (95xa0% CI 4.9–8.5xa0months) in the paclitaxel arm, whereas the median OS was 10.5xa0months (95xa0% CI 9.2–11.9xa0months) in the cisplatin arm and 13.2xa0months (95xa0% CI 9.4–17.0xa0months) in the paclitaxel arm. Patients in the cisplatin arm were more likely to experience neutropenia and thrombocytopenia, whereas patients in the paclitaxel arm had a higher frequency of neuropathy and alopecia. Quality of life was similar between treatment arms.ConclusionsBoth CC and CP regimens were effective and well tolerated as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma.

680PPHASE II STUDY OF A COMBINATION CHEMOTHERAPY WITH WEEKLY DOCETAXEL AND GEMCITABINE IN PREVIOUSLY TREATED METASTATIC ESOPHAGEAL SQUAMOUS CELL CANCER

ABSTRACT Aim: This multicenter, phase II study was conducted to assess the efficacy and safety of weekly docetaxel plus fixed-dose rate (FDR) gemcitabine as second-line chemotherapy in patients with metastatic esophageal squamous cell carcinoma (SCC). Methods: Esophageal SCC patients with documented progression after fluoropyrimidine-based first-line chemotherapy were treated with docetaxel 35u2003mg/m2 and gemcitabine 1,000u2003mg/m2 iv at FDR (10u2003mg/m2/min) on days 1 and 8. Treatment was repeated every 21 days until disease progression, unacceptable toxicity, or consent withdrawal. Primary endpoint was response rate (RR), and secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS). Results: A total of 33 patients were registered onto this prospective study. Combination or weekly docetaxel and FDR gemcitabine was well tolerated: the most common treatment-related adverse events were anemia (97%), fatigue (64%) and neutropenia (55%). Grade 3 or 4 neutropenia was developed in 13 patients (39%) and three episodes of febrile neutropenia were observed. One patient with lung and extensive lymph node metastases died of respiratory failure after receiving fourth cycles of chemotherapy, and the possibility of drug-induced pneumonitis could not be completely excluded. The overall RR was 30% with one complete and 9 partial responses. Stable disease was documented in 19 patients (58%). The median PFS and OS were 6 (95% CI 5-8) and 9 (95% CI 7-11) months, respectively. Conclusions: The weekly combination of docetaxel and FDR gemcitabine showed a promising antitumor activity and tolerability in previously treated, metastatic esophageal SCC. Disclosure: All authors have declared no conflicts of interest.