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Comparison of T790M Acquisition Between Patients Treated with Afatinib and Gefitinib as First-Line Therapy: Retrospective Propensity Score Matching Analysis.

ABSTRACT: Afatinib, a second-generation, irreversible pan-HER inhibitor, shows better suppression of T790M-positive lung cancer cells than gefitinib in preclinical studies. However, whether the effect of afatinib on T790M acquisition differs from that of gefitinib when used clinically as first-line therapy remains unclear. To reaffirm the preclinical efficacy of afatinib on T790M-positive lung cancer cells, H1975 cells and established PC-9 cells resistant to gefitinib and erlotinib by T790M were used. In total, 398 patients with second biopsy at progression with stage IIIB/IV non-small cell lung cancer with EGFR mutation, treated with afatinib or gefitinib as first-line therapy, were retrospectively reviewed. Propensity score matching was used to balance covariates. Afatinib inhibited the growth of lung cancer cells with low T790M allele frequencies, which are resistant to gefitinib, but not those with high T790M allele frequencies. Afatinib and gefitinib showed similar efficacy in terms of progression-free survival (PFS) (11.5 vs 13.4?months, P?=?.08) and overall survival (OS) (29.3 vs 28.5?months, P?=?.76). T790M patients had better PFS and OS than those without T790M. There was no significant difference in the cumulative T790M acquisition ratio over time between afatinib and gefitinib (48.8% vs 59.3%, P?=?.317). The median time to acquire T790M was 12.9?months for afatinib and 15.7?months for gefitinib (P?=?.342). Although afatinib inhibited the growth of lung cancer cells with low T790M allele frequencies in preclinical studies, this could not be translated into clinical efficacy in terms of lowering the rate or delaying the time of T790M acquisition.

SUBMITTER: Yoon BW

PROVIDER: S-EPMC6484288 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Comparison of T790M Acquisition Between Patients Treated with Afatinib and Gefitinib as First-Line Therapy: Retrospective Propensity Score Matching Analysis.

Yoon Byung Woo BW Kim Jae Hoon JH Lee Seung Hyeon SH Choi Chang-Min CM Rho Jin Kyung JK Yoon Shinkyo S Lee Dae Ho DH Kim Sang-We SW Jang Tae-Won TW Lee Jae Cheol JC

Translational oncology 20190425 6

Afatinib, a second-generation, irreversible pan-HER inhibitor, shows better suppression of T790M-positive lung cancer cells than gefitinib in preclinical studies. However, whether the effect of afatinib on T790M acquisition differs from that of gefitinib when used clinically as first-line therapy remains unclear. To reaffirm the preclinical efficacy of afatinib on T790M-positive lung cancer cells, H1975 cells and established PC-9 cells resistant to gefitinib and erlotinib by T790M were used. In ...[more]

PMID: 31030101

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Project description:ObjectiveDuring the past decade, the concept of complete mesocolic excision (CME) has been developed in an attempt to minimize recurrence for right-sided colon cancer. This study aims to compare outcomes of robotic versus laparoscopic right hemicolectomy with CME for right-sided colon cancer.MethodsWe performed a retrospective multicenter propensity score matching study. From July 2016 to July 2021, 382 consecutive patients from different Chinese surgical departments were available for inclusion out of an initial cohort of 412, who underwent robotic or laparoscopic right hemicolectomy with CME. Data of all patients were retrospectively collected and reviewed. Of these, 149 cases were performed by a robotic approach, while the other 233 cases were done by laparoscopy. Propensity score matching was applied at a ratio of 1:1 to compare perioperative, pathologic, and oncologic outcomes between the robotic and the laparoscopic groups (n = 142).ResultsBefore propensity score matching, there were no statistical differences regarding the sex, history of abdominal surgery, body mass index (BMI), American Joint Committee on Cancer (AJCC) staging system, tumor location, and center between groups (p > 0.05), while a significant difference was observed regarding age (p = 0.029). After matching, two comparable groups of 142 cases were obtained with equivalent patient characteristics (p > 0.05). Blood loss, time to oral intake, return of bowel function, length of stay, and complications were not different between groups (p > 0.05). The robotic group showed a significantly lower conversion rate (0% vs. 4.2%, p = 0.03), but a longer operative time (200.9 min vs. 182.3 min, p < 0.001) and a higher total hospital cost (85,016 RMB vs. 58,266 RMB, p < 0.001) compared with the laparoscopic group. The number of harvested lymph nodes was comparable (20.4 vs. 20.5, p = 0.861). Incidence of complications, mortality, and pathologic outcomes were similar between groups (p > 0.05). The 2-year disease-free survival rates were 84.9% and 87.1% (p = 0.679), and the overall survival rates between groups were 83.8% and 80.7% (p = 0.943).ConclusionDespite the limitations of a retrospective analysis, the outcomes of robotic right hemicolectomy with CME were comparable to the laparoscopic procedures with fewer conversions to open surgery. More clinical advantages of the robotic surgery system need to be further confirmed by well-conducted randomized clinical trials with large cohorts of patients.

Project description:ObjectiveThe aim of the study was to evaluate the efficacy and toxicity of prophylactic extended-field radiation therapy (RT) for cervical cancer patients treated with concurrent chemoradiotherapy (CCRT).MethodsRecords of patients with cervical cancer without para-aortic metastatic lymph nodes who were treated with definitive RT or CCRT between January 2011 and December 2014 were reviewed. Patients were classified into the pelvic RT and extended-field RT groups. An additional dose of 50.4 Gy in 28 fractions was delivered to para-aortic lymph node regions for patients in the extended-field RT group. Cox regression and propensity-score matching (1:1) were used to compare the overall survival (OS), disease-free survival (DFS), distant failure, and para-aortic lymph node failure (PALNF) between the pelvic RT and extended-field RT groups.ResultsA total of 778 patients were analyzed. Of them, 624 patients were treated with pelvic RT and 154 patients received extended-field RT. The median follow-up period was 37.5 months. In multivariate analysis, extended-field RT was an independent prognostic factor of distant failure (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.26-0.90, P = 0.023) and PALNF (HR = 0.012, 95% CI = 0.00-0.49, P = 0.019). However, it was not significant in predicting OS (P = 0.546) and DFS (P = 0.187). With propensity-score matching, 108 pairs of patients were selected. The 3-year OS, DFS, local control, distant failure, and PALNF rates in the pelvic RT and extended-field RT groups were 87.1% and 85.7% (P = 0.681), 71.0% and 80.6% (P = 0.199), 86.6% and 85.0% (P = 0.695), 21.7% and 7.0% (P = 0.016), and 6.6% and 0% (P = 0.014), respectively. The incidences of grade 3 or greater chronic toxicities were 3.5% and 6.5% in the pelvic RT and extended-field RT groups, respectively (P = 0.097).ConclusionsProphylactic extended-field RT was associated with decreased distant failure and PALNF and showed a trend in improving DFS in patients with cervical cancer treated with CCRT.

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Project description:Previous evidence revealed that central obesity played a vital role in the development of diabetes mellitus (DM). However, because of imbalanced confounding variables, some studies have not wholly established the association between central obesity and diabetes. Propensity score matching (PSM) analysis can minimize the impact of potential confounding variables. Therefore, the aim of the present study was to explore the relationship between central obesity and diabetes in the Japanese population by using PSM analysis. This retrospective cohort study included 15,453 Japanese adults who were free of diabetes at baseline between 2004 and 2015, which provided all medical records for individuals participating in the physical exam. Central obesity at baseline was an independent variable, and incident diabetes during follow-up was an outcome variable. Using a 1:1 PSM analysis, the present retrospective cohort study included 1639 adults with and without central obesity. Additionally, we employed a doubly robust estimation method to identify the association between central obesity and diabetes. Subjects with central obesity were 92% more likely to develop DM (HR = 1.65, 95%CI 1.12, 2.41). After adjusting for covariates, subjects with central obesity had a 72% increased risk of developing DM compared with subjects with non-central obesity in the PSM cohort (HR = 1.72, 95% CI 1.16, 2.56). Central obesity individuals had a 91% higher risk of DM than non-central obesity individuals, after adjustment for propensity score (HR = 1.91, 95% CI 1.29, 2.81). In sensitivity analysis, the central obesity group had a 44% (HR = 1.44, 95% CI 1.09, 1.90) and 59% (HR = 1.59, 95% CI1.35, 1.88) higher risk of DM than the non-central obesity group in the original and weighted cohorts after adjusting for confounding variables, respectively. Central obesity was independently associated with an increased risk of developing diabetes. After adjustment for confounding covariates, central obesity participants had a 72% higher risk of development of diabetes than non-central obesity individuals in the PSM cohort.

Dataset Information

Comparison of T790M Acquisition Between Patients Treated with Afatinib and Gefitinib as First-Line Therapy: Retrospective Propensity Score Matching Analysis.

Publications

Comparison of T790M Acquisition Between Patients Treated with Afatinib and Gefitinib as First-Line Therapy: Retrospective Propensity Score Matching Analysis.

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