Erlotinib-based targeted dual agent versus erlotinib alone in previously treated advanced non-small-cell lung cancer: a meta-analysis of 13 randomized controlled trials

Objectives: To compare the effects of an erlotinib-based targeted dual agent with erlotinib alone in previously treated patients with advanced non-small lung cancer (NSCLC).

Patients and methods: The PubMed and Embase databases and the Cochrane Central Register of Controlled Trials were searched for publications between January 2005 and March 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed.

Results: Thirteen trials with a total of 4509 patients were included in this meta-analysis. Compared with erlotinib alone, combination therapy showed no improvement in OS (HR?=?0.95; 95% CI, 0.89–1.02; P?=?.132) though significantly prolonged PFS (HR?=?0.82; 95% CI, 0.75–0.90; P?<?.001). Combination therapy significantly increased ORR (RR?=?1.32; 95% CI, 1.09–1.60; P?=?.005) and DCR (RR?=?1.26; 95% CI, 1.17–1.36, P?<?.001). Sub-analysis assessment failed to identify any sub-groups which could benefit from combination therapy in terms of OS. Combination therapy was associated with more grade 3 or higher toxic effects (RR?=?1.54; 95% CI, 1.22–1.95; P?<?.001). Patients treated with combination therapy had more grade 3 or greater fatigue (RR?=?1.49; 95% CI, 1.16–1.91; P?=?.002), but did not develop more diarrhea (RR?=?2.02; 95% CI, 0.86–4.77; P?=?.107) or rash (RR?=?1.29, 95% CI, 0.90–1.85; P?=?.172). This study had limitations about heterogeneities among the included trials, and the analysis was not based on individual patient data.

Conclusions: Compared with erlotinib alone, the erlotinib-based targeted dual agent showed a minimal magnitude of improvement in PFS but did not improve OS. The role of erlotinib-based combinations in previously treated patients with NSCLC seemed insignificant.     

Matching-adjusted indirect comparison of bosutinib,dasatinib and nilotinib effect on survival and major cytogenetic response in treatment of second-line chronic phase chronic myeloid leukemia

Objective: In clinical trials of second-line therapies for chronic phase chronic myeloid leukemia (CP-CML), to date, only single-arm trials have been conducted for the available tyrosine kinase inhibitor treatments (bosutinib, dasatinib and nilotinib). These trials included heterogeneous patient populations in terms of disease and baseline characteristics. These hamper the use of standard network meta-analyses for indirect treatment comparison of relative efficacy. In this situation, a matching-adjusted indirect comparison (MAIC) in second-line CP-CML was performed. The aim was to compare the relative efficacies of bosutinib, dasatinib and nilotinib in second-line CP-CML patients.

Methods: The MAIC was preceded by a systematic literature review that ensured inclusion of the underlying data for the analyses. The outcomes were measured in terms of overall survival (OS), progression-free survival (PFS) and major cytogenetic response (MCyR). The treatments were quantitatively compared based on Cox proportional hazard ratio (HR) regressions, on restricted mean survival (RMST, when the proportionality assumption showed evidence of violation) and on odds ratios (for response measures).

Results: Comparing with dasatinib, bosutinib resulted in HRs for PFS and OS of 0.63 (0.44–0.90, p?<?.05) and 0.82 (0.54–1.26, p?=?.37) respectively, and resulted in an OR for MCyR of 0.78 (0.53–1.16). Although the proportionality of hazards assumption was violated for PFS, the RMST analyses confirmed the findings of the Cox regression. When compared with nilotinib, bosutinib showed a significant HR of 0.54 (0.38–0.76, p?<?.01) in favor of bosutinib for PFS, a non-significant HR of 0.72 (0.46–1.13, p?=?.16) for OS and a non-significant OR of 0.98 (0.71–1.35) for MCyR.

Conclusions: Bosutinib had a significantly greater PFS than both dasatinib and nilotinib. For OS, the findings were numerically in favor of bosutinib, but not statistically significant. For MCyR, the findings were numerically in favor of dasatinib and nilotinib, but not statistically significant.     

Efficacy and safety of doublet versus single agent as salvage treatment for metastatic breast cancer pretreated with anthracyclines and taxanes: a systematic review and meta-analysis

Aim: To perform a systematic review and meta-analysis of randomized controlled trials to compare the efficacy and safety of doublet versus single agent as salvage treatment for pretreated metastatic breast cancer.

Methods: A comprehensive literature search was performed to identify relevant randomized controlled trials (RCTs). All clinical studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive MetaAnalysis software (Version 2.0).

Results: Thirteen RCTs involving 4878 pretreated metastatic breast cancer patients were ultimately identified. The pooled results demonstrated that doublet combination therapy significantly improved ORR (RR 1.13, 95% CI: 1.01–1.27, p?<?.001) and PFS (hazard ration [HR] 0.83, 95% CI: 0.73–0.96, p?=?.011), but not OS (HR 0.93, 95% CI: 0.86–1.01, p?=?.065). Similar results were observed in sub-group analysis according to treatment regimens. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities nausea and fatigue were observed in doublet combination therapy.

Conclusions: In comparison with a single agent alone, doublet combination therapy as salvage treatment for pretreated metastatic breast cancer patients significantly improves ORR and PFS, but not OS. Further studies are recommended to identify patients who will most likely benefit from the appropriate doublet combination therapy.     

The value of surrogate endpoints for predicting real-world survival across five cancer types

Objective It is unclear how well different outcome measures in randomized controlled trials (RCTs) perform in predicting real-world cancer survival. We assess the ability of RCT overall survival (OS) and surrogate endpoints – progression-free survival (PFS) and time to progression (TTP) – to predict real-world OS across five cancers.

Methods We identified 20 treatments and 31 indications for breast, colorectal, lung, ovarian, and pancreatic cancer that had a phase III RCT reporting median OS and median PFS or TTP. Median real-world OS was determined using a Kaplan–Meier estimator applied to patients in the Surveillance and Epidemiology End Results (SEER)-Medicare database (1991–2010). Performance of RCT OS and PFS/TTP in predicting real-world OS was measured using t-tests, median absolute prediction error, and R² from linear regressions.

Results Among 72,600 SEER-Medicare patients similar to RCT participants, median survival was 5.9 months for trial surrogates, 14.1 months for trial OS, and 13.4 months for real-world OS. For this sample, regression models using clinical trial OS and trial surrogates as independent variables predicted real-world OS significantly better than models using surrogates alone (P?=?0.026). Among all real-world patients using sample treatments (N?=?309,182), however, adding trial OS did not improve predictive power over predictions based on surrogates alone (P?=?0.194). Results were qualitatively similar using median absolute prediction error and R² metrics.

Conclusions Among the five tumor types investigated, trial OS and surrogates were each independently valuable in predicting real-world OS outcomes for patients similar to trial participants. In broader real-world populations, however, trial OS added little incremental value over surrogates alone.     

Angiogenesis inhibitors for patients with ovarian cancer: a meta-analysis of 12 randomized controlled trials

Objectives:

To investigate the effects of angiogenesis inhibitors in the treatment of patients with advanced or recurrent ovarian cancer, a meta-analysis was performed and overall survival (OS), progression-free survival (PFS), and toxicity were assessed.

Patients and methods:

The PubMed and Embase databases, and the Cochrane Central Register of Controlled Trials were searched for publications between January 2000 and June 2015. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived.

Results:

The 12 trials in this meta-analysis were divided into three groups: four trials with a VEGF inhibitor (the bevacizumab group), six trials with VEGFR inhibitors (the VEGFRIs group), and two trials with an angiopoietin inhibitor (the trebananib group). PFS improvement was seen in all groups (HR?=?0.61, 95% CI 0.48 to 0.79, P?<?0.001 for bevacizumab; HR?=?0.71, 95% CI 0.59 to 0.87, P?=?0.001 for VEGFRIs; and HR?=?0.67, 95% CI 0.62 to 0.72, P?<?0.001 for trebananib). Regarding OS, bevacizumab showed a trend of improvement (HR?=?0.90, 95% CI 0.80 to 1.01, P?=?0.079), VEGFRIs showed no improvement (HR?=?0.92, 95% CI 0.75 to 1.11, P?=?0.368), and trebananib demonstrated a significant prolongation (HR?=?0.81, 95% CI 0.67 to 0.99, P?=?0.036). Bevacizumab was associated with more class-specific adverse events (RR?=?4.05, 95% CI 1.99 to 8.27, P?<?0.001). Although the toxicity profiles differed, VEGFRIs developed common higher incidences of hypertension, diarrhea, and fatigue. A higher incidence of edema was reported in the trebananib group (RR?=?2.60, 95% CI 0.84 to 8.00, P?=?0.097).

Conclusions:

Anti-angiogenic therapy showed clear PFS benefit with increased toxicity, but its role in OS was undefined for ovarian cancer which emphasized the need for patient selection.     

Treatment outcome of docetaxel,capecitabine and cisplatin regimen for patients with refractory and relapsed nasopharyngeal carcinoma who failed previous platinum-based chemotherapy

Objective: Although cisplatin combined with 5-fluorouracil is a common first-line regimen for advanced nasopharyngeal carcinoma (NPC), there are no standard regimens for refractory or relapsed patients. A study of DXD regimen [cisplatin (D), capecitabine (X) and docetaxel (D)] was conducted to evaluate the efficacy and toxicity for patients with refractory or relapsed NPC.

Methods: The regimen was administered as follows: 50 mg/m² docetaxel and 50 mg/m² cisplatin on day 1 and 800 mg/m² capecitabine on days 1 – 14, repeated every 3 – 4 weeks.

Results: Thirty patients were enrolled. The overall response and complete remission rate was 46.4 and 21.4%. Median follow-up was 24 months; median overall survival (OS) and progression-free survival (PFS) were 14.0 and 8.0 months. Five-year OS and PFS rates were 14.8 and 13.3%, respectively. Four patients achieved long-term tumor-free survival (range, 53.8 – 125.3 months). Multivariate analysis demonstrated that Epstein–Barr virus DNA status (p = 0.003) and therapeutic effect (p < 0.001) were significant independent factors for OS and PFS. The main grade 3/4 toxicities included neutropenia (26.6%), anemia (13.3%) and thrombocytopenia (10.0%). There were no chemotherapy-related deaths.

Conclusion: The DXD regimen appeared to be effective and well tolerated by patients with refractory or relapsed NPC. Further investigation is warranted.     

分子靶向药物治疗晚期胃肠道间质瘤的安全性及有效性分析

目的 系统评价分子靶向药物——伊马替尼、舒尼替尼、瑞戈非尼、尼洛替尼和帕唑帕尼对比安慰剂或最佳支持治疗治疗晚期或转移性胃肠道间质瘤（gastrointestinal stromal tumour,GIST）的有效性与安全性。方法 计算机检索Pubmed、Embase、Cochrane Library、中国知网、万方数据库和维普等数据库,按照文献纳入标准和排除标准选择应用分子靶向药物治疗GIST的临床研究,RevMan 5.3软件进行meta分析。其中,试验组为近年来相继上市的酪氨酸激酶抑制剂分子靶向药物——伊马替尼、舒尼替尼、瑞戈非尼、尼洛替尼和帕唑帕尼,对照组为安慰剂或最佳支持治疗。观察终点包括无进展生存期（progression-free survival,PFS）、总生存期（overall survival,OS）和3~4级不良反应发生率。结果 共纳入7项临床研究,总样本量为1 528例。Meta分析结果显示,分子靶向药物与对照组相比,PFS时间（HR=0.34,95%CI：0.26~0.44,P<0.001）,OS时间（HR=0.38,95%CI：0.17~0.85,P<0.02）均明显延长。在不良反应方面,分子靶向药物组可使3~4级不良反应（RR=4.47,95%CI：2.12~9.39,P<0.000 1）的发生率明显增高,主要是中性粒细胞减少、高血压、手足综合征、皮疹、腹泻和疲劳。结论 分子靶向药物治疗晚期或转移性GIST可以延长患者的PFS和OS。虽然其不良反应发生率高于对照组,但患者仍可耐受。     

塞来昔布联合化疗对转移性或术后复发性晚期胃癌的疗效及药物不良反应

目的 分析塞来昔布联合化疗治疗转移性或术后复发性胃癌的疗效和安全性。方法 收集2010年9月至2016年12月转移性或术后复发性胃癌患者,分为塞来昔布+化疗组和单纯化疗组,治疗6个周期。比较两组患者间临床资料、无进展生存期（PFS）、总生存期（OS）的差异,并进一步分析COX-2阳性亚组的生存情况,评价药物安全性。结果 共纳入患者176例,塞来昔布+化疗组89例,单纯化疗组87例。两组患者客观缓解率、疾病控制率比较,差异均无统计学意义（P>0.05）。两组患者中位OS（P=0.59）和中位PFS（P=0.734）比较,差异均无统计学意义。塞来昔布+化疗组COX-2阳性患者中位OS为14个月,单纯化疗组COX-2阳性患者为10个月,差异有统计学意义（P=0.010）;塞来昔布+化疗组COX-2阳性患者中位PFS为7.5个月,单纯化疗组COX-2阳性患者为5个月,差异有统计学意义（P<0.001）。两组患者的药物不良反应均以恶心最为常见,但差异无统计学意义。结论 塞来昔布联合化疗可延长COX-2阳性晚期胃癌患者的OS和PFS,且不增加药物不良反应。     

氨柔比星用于小细胞肺癌二线治疗的荟萃分析

目的 系统评价氨柔比星治疗小细胞肺癌（small-cell lung cancer, SCLC）的疗效及安全性。方法 检索PubMed、EMBASE、CNKI及The Cochrane Library等数据库,收集有关氨柔比星治疗SCLC的研究;主要结局指标包括总有效率（overall response rate,ORR）、无进展生存率（progression free survival, PFS）、总生存率（overall survival, OS）及不良事件。结果 共有6项研究纳入,荟萃分析（Meta分析）显示,氨柔比星应用于SCLC二线治疗时的总有效率显著高于对照组[RR 1.72,95% CI（1.39,2.14）,P=0.000],但总生存率[HR 0.93,95% CI（0.81,1.07）,P=0.405]和无进展生存率[HR 0.98,95% CI（0.83,1.17）,P=0.456]与对照组相比无明显差异。结论 氨柔比星治疗SCLC的总有效率高于对照组,且PFS和OS与对照组相比无显著性差异（P=0.405,P=0.456）,因此,氨柔比星可作为SCLC的二线治疗药物。     

Epidermal growth factor receptor tyrosine kinase inhibitors in previously treated advanced non-small-cell lung cancer with wild-type EGFR

Introduction: While epidermal growth factor receptor (EGFR) – tyrosine kinase inhibitors (TKIs) lead to longer progression-free survival (PFS) when compared with conventional chemotherapy in non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR-TKI remains unclear in EGFR-wild-type (WT) NSCLC.

Areas covered: This article reviews selected data from randomized trials regarding the use of TKIs in EGFR-WT NSCLC. Nine randomized phase III trials have compared EGFR-TKI with chemotherapy in NSCLC patients in a second or later line setting. Two of these trials, TAILOR and DELTA, which were designed to investigate treatment benefits according to EGFR genotype, demonstrated that docetaxel chemotherapy displayed significantly better in progression-free survival (PFS) when compared with the EGFR-TKI erlotinib. Biomarkers to predict clinical benefits of the drug against EGFR WT tumor, and the efficacy of combination regimens using erlotinib or single-use afatinib against tumors are also covered in this article.

Expert opinion: Considering the modest benefits of erlotinib for EGFR-WT tumors, future studies are warranted, including the exploration of useful biomarkers and new treatment strategies for EGFT-TKI use, as well as the development of more sensitive EGFR mutation tests.     

A triplet chemotherapy regimen of cisplatin,fluorouracil and paclitaxel for locoregionally recurrent nasopharyngeal carcinoma cases contraindicated for re-irradiation/surgery

Objective: Salvage treatment for locoregionally recurrent nasopharyngeal carcinoma remains a significant challenge. The present study was conducted to evaluate the efficacy, toxicity and prognostic factors of a triplet chemotherapy regimen involving cisplatin, fluorouracil and paclitaxel (TPF) for locoregionally recurrent nasopharyngeal carcinoma (NPC) cases contraindicated for re-irradiation/surgery.

Methods: Patients with locoregionally recurrent NPC unsuitable for re-irradiation/surgery were treated with TPF therapy. The chemotherapy drugs were administered as follows: 135 mg/m² paclitaxel on day 1, 25 mg/m²/day cisplatin on days 1–3, followed by continuously infused intravenous fluorouracil for 120 h at a variable dosage from 600 to 800 mg/m²/day, depending on prior radiation.

Results: Twenty-seven patients were enrolled. The overall response was 66.7%. The median progression-free survival (PFS) and overall survival (OS) were 8.5 and 27.2 months, respectively. Toxicity was mild to moderate. Neutropenia and leukopenia were the primary grade 3–4 chemotherapy toxicities. 6 patients who regained the potential for re-radiotherapy or surgery showed significantly better outcomes than those treated with chemotherapy alone (median PFS: 20.8 vs. 7.1 months, P = 0.005; median OS: 54.2 vs. 20.6 months, P = 0.021).

Conclusion: TPF triplet chemotherapy showed a high response rate for locoregionally recurrent NPC with an acceptable toxicity profile.     

Comparison of clinicopathological and prognostic characteristics in patients with mucinous carcinoma and signet ring cell carcinoma of the stomach

Aim: To determine whether there are any clinicopathological or prognostic differences between mucinous gastric carcinoma (MGC) and signet ring cell carcinoma (SRCC).

Methods: Pathological parameters, clinical parameters, and treatment efficacy were compared in patients with MGC and SRCC.

Results: In total, 193 patients (51 with MGC and 142 with SRCC) were included in this study. Patients with SRCC in particular had notably higher lymphovascular invasion, perineural invasion, rate of Borrmann types III and IV, and stage III–IV cancer (according to its TNM stage) compared with patients with MGC. However, tumor size was larger in patients with MGC (tumor size ≥5?cm). Median overall survival (OS) was 29.8 months in the MGC group and 16.6 months in the SRCC group (p?=?.04). The median OS in stage I–III patients was 59.9 and 42.5 months in the MGC and SRCC groups, respectively (p?=?.35). Comparing OS between MGC and SRCC stage IV patients revealed that the median OS was 10.1 and 8.8 months, respectively (p?=?.96). Multivariate analysis of the entire patient group revealed that the presence of weight loss at diagnosis, distant metastasis, and lymph node involvement were significantly related to OS. Multivariate analysis also revealed that weight loss at the diagnosis and T3–4 tumors were significant factors influencing OS in the stage I–III group.

Conclusions: Patients with SRCC had generally poorer prognosis and lower survival rates compared with patients with MGC. Further studies on the prognosis and treatment plan based on the pathological subtypes of SRCC and MGC are still needed.     

Prognostic importance of the albumin to globulin ratio in metastatic gastric cancer patients

Aim: The aim of this study was to evaluate the prognostic importance of the albumin to globulin ratio (AGR) in terms of overall survival (OS) and progression free survival (PFS) in metastatic gastric cancer patients.

Methods: The patients diagnosed with metastatic gastric cancer between 2009 and April 2016 at the hospital have been studied retrospectively. The clinicopathological characteristics, laboratory, and treatment parameters have been assessed. AGR value has been calculated using the following formula (AGR?=?serum albumin/total protein???serum albumin).

Results: In total, 251 patients were included in the study population. The median value of AGR was 1.206 (range?=?0.460–3.130), and the cut-off value was set as 1.20. Based on the cut-off value, 126 patients were categorized in the low AGR group, while the remaining 125 patients were categorized in the high AGR group. ECOG (Eastern Cooperative Oncology Group) performance scores, CEA levels, CA19-9 levels, hemoglobin levels, lactate dehydrogenase levels, and liver metastasis ratios varied significantly between the low and high AGR groups (p?<?.05). The Kaplan-Meier curve has shown that, compared to the low AGR group, the high AGR group has better OS (12.2 vs 9.3 months, p?=?.002) and better PFS (8.0 vs 5.7 months, p?<?.001) rates. The univariate and multivariate analyses also proved that low AGR is an independent bad risk factor in metastatic gastric cancer patients, both in terms of OS (p?=?.019, Hazard Ratio (HR)?=?1.380, 95% Confidence Interval (CI)?=?1.055–1.805) and PFS (p?=?.002, HR?=?1.514, 95% CI?=?1.164–1.968).

Conclusion: In metastatic gastric cancer patients, AGR is an independent prognostic factor for OS and PFS. Thus, in this patient group, the low cost albumin and globulin which can be measured with routine clinical practice may be used as an appropriate prognostic tool.     

The prognostic role of FIGO stage in patients with vulvar cancer: a systematic review and meta-analysis

Objective: To perform a meta-analysis examining the survival of patients with vulvar cancer based on the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system. Methods: Medline, PubMed, and Cochrane databases were searched until 20 March 2015 for prospective or retrospective studies using the terms vulvar cancer, prognostic/prognosis, survival, recurrence, lymph nodes (LNs), inguinal lymphadenectomy/excision, and staging. The primary outcome was 5 year overall survival (OS), and secondary outcomes were 5 year disease-free survival (DFS) and progression-free survival (PFS). Results: Fourteen retrospective studies were included. The 5 year OS rate decreased with increasing 2009 FIGO stage and number of LN metastasis. FIGO stage I, II, III, and IV patients had 5 year OS rates of 84.0%, 74.6%, 47.8%, and 9.4%, respectively. Pooled estimates showed that the 5 year OS was 84.5% for patients without LN metastasis, and for patients with ≥3 LN metastases the 5 year OS rate was 30.1%. Similarly, the overall 5 year DFS and PFS decreased with the increasing number of LN metastases. The 5 year DFS rate was 87.2% for patients with no LN metastasis and for patients with ≥3 LN metastases was 35.4%. The 5 year PFS rate was 86.6% for patients with no LN metastasis and for patients with ≥3 LN metastases was 27.6%. Limitations: All studies were retrospective studies. DFS and PFS rates in patients with different 2009 FIGO stages and with different mean tumor sizes were not examined due to a limited number of reports. Conclusions: More advanced 2009 FIGO stage and greater number of LN metastases are associated with worse outcomes in patients with vulvar cancer.     

Real-world use of osimertinib in non–small cell lung cancer: ASTRIS study Korean subgroup analysis

Abstract

Objective: ASTRIS is a large real-world, open-label, multinational clinical study of osimertinib in patients with epidermal growth factor receptor (EGFR) T790M mutation-positive advanced non-small cell lung cancer (NSCLC) who have previously received a tyrosine kinase inhibitor (TKI). We report data from the Korean ASTRIS subgroup.

Methods: Adult patients with locally advanced or metastatic NSCLC with a confirmed T790M mutation, WHO performance status of 0–2 and prior EGFR-TKI therapy, received osimertinib 80?mg once daily. Efficacy outcomes were overall survival (OS), investigator-assessed response rate (RR) and progression-free survival (PFS), and time to treatment discontinuation (TTD).

Results: At data cut-off (20 October 2017), 466 Korean patients were enrolled. Baseline EGFR molecular testing was mainly performed on biopsied tissue (75.1%). Baseline mutations co-occurring with T790M included exon 19 deletions (60.7%) and L858R (32.8%). 1-year OS was 82.7% (OS data not matured at data cut-off). Overall, RR was 71.0%, median PFS was 12.4?months and median TTD was 15.0?months. In patients with/without CNS metastases, RR was 68.0% and 79.6%, respectively; median PFS, 10.8 and 11.0?months, respectively; and median TTD, 11.2 and 14.7?months, respectively. Overall, 31.1% of patients experienced ≥1 adverse event (AE), leading to dose modification (12.0%), discontinuation (5.2%) or death (2.8%). Serious AEs (24.9%) included pulmonary embolism (1.7%), pleural effusion (1.7%), and pneumonia (1.5%).

Conclusion: In this real-world subgroup analysis of Korean patients in the ASTRIS study, osimertinib demonstrated comparable clinical efficacy to that attained in the global ASTRIS study and other clinical trials, with no new safety concerns.     

Adjuvant docetaxel and carboplatin chemotherapy administered alone or with radiotherapy in a “sandwich” protocol in patients with advanced endometrial cancer: a single-institution experience

Objective: To evaluate the outcomes of adjuvant chemotherapy administered alone or with radiotherapy in a “sandwich” protocol in patients with advanced endometrial cancer.

Methods: The authors retrospectively reviewed the clinical records of patients with staged III – IV disease who received adjuvant chemotherapy (docetaxel plus carboplatin) administered alone or interposed with radiotherapy between January 2004 and August 2010.

Results: Of the 35 study patients, 10 (28.6%) had stage IIIA disease, 15 (42.9%) had IIIC1 disease, 7 (20.0%) had IIIC2 disease and 3 (8.6%) had IVB disease. Nine (90.0%) of the 10 patients with stage IIIA disease received four to six cycles of adjuvant docetaxel and carboplatin chemotherapy alone. All 25 patients with stage IIIC – IVB disease and 1 patient with stage IIIA disease received radiotherapy sandwiched between chemotherapy cycles (total, three to six cycles). The 3-year progression-free survival (PFS) and overall survival (OS) rates were 73.0 and 87.0%, respectively, for all patients. For patients with stage IIIC – IVB disease, the 3-year PFS and OS rates were 62.4 and 81.8%, respectively.

Conclusion: Combination chemotherapy with docetaxel and carboplatin interposed with radiotherapy is efficacious and well tolerated for stage IIIC – IVB endometrial cancer. Adjuvant chemotherapy alone with docetaxel and carboplatin might be sufficient for stage IIIA disease.     

Comparative effectiveness of everolimus and axitinib as second targeted therapies for metastatic renal cell carcinoma in the US: a retrospective chart review

Background Second targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin inhibitors (mTORis) and tyrosine kinase inhibitors (TKIs). This observational study compares overall survival (OS) and progression-free survival (PFS) of patients treated with everolimus (an mTORi) and axitinib (a TKI) following first TKI, and assesses the impact of type and duration of first TKI on the relative effectiveness of these second targeted therapies.

Methods Retrospective reviews of medical records were conducted by medical oncologists or hematologists/oncologists recruited from a nationwide panel. Included patients with mRCC were required to have discontinued a first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons, and to have initiated everolimus or axitinib as second targeted therapy between February 2012 and January 2013. OS and PFS were compared between patients treated with everolimus vs. axitinib using multivariable Cox proportional hazards regression models. Comparative results were also stratified by type and duration of first TKI.

Results Included patients (n?=?325 for everolimus and n?=?127 for axitinib) had a mean age of 61 years and 31% were female. Sunitinib was the most commonly used first TKI (73%). After adjusting for patient characteristics, no statistically significant differences were observed in OS or PFS between everolimus and axitinib. When stratifying by type and duration of first TKI, there was no statistically significant difference in OS between everolimus and axitinib in all subgroups except for patients with?<6 months on sunitinib or sorafenib as first TKI. No significant difference in PFS was observed in any subgroup.

Limitations Important limitations include potential missing or inaccurate data in medical charts, and confounding due to unobserved factors.

Conclusions In this retrospective chart review, no significant differences were detected in OS or PFS between axitinib and everolimus as second targeted therapy. Longer duration of first TKI was not associated with increased effectiveness of subsequent axitinib compared to everolimus.     

Comparing nilotinib with dasatinib as second-line therapies in patients with chronic myelogenous leukemia resistant or intolerant to imatinib – a retrospective chart review analysis

Abstract

Introduction:

This study compared progression, progression-free survival (PFS), overall survival (OS), and treatment changes among chronic myelogenous leukemia patients in chronic phase (CML-CP) receiving nilotinib or dasatinib as second-line therapy.     

Adenocarcinoma histology is a poor prognostic factor in locally advanced cervical cancer

Objective: This retrospective study aimed to compare prognostic factors and survival between adenocarcinoma (AC) and squamous cell carcinoma (SCC) in locally advanced cervical cancer treated at a single center.

Methods: All medical records of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB or IIIA,B, treated between 2004 and 2012, were reviewed. We treated patients with chemoradiotherapy (CRT) followed by brachytherapy (BT). Multivariate logistic regression and Cox proportional hazard models were used to analyze clinicopathological characteristics, patterns of care and outcomes.

Results: We included in the analysis 161 patients (52 AC; 109 SCC). Patients with AC were younger (age 50 vs. 55?years), more likely to die from the disease (HR: 1.60; 95% CI: 1.26–2.58; p?=?.001) and to have disease recurrence (HR: 1.69; 95% C.I: 1.21–2.12; p?=?.004) than those with SCC. The other significant prognostic factors for overall survival (OS) and recurrence-free survival (RFS) in AC were FIGO stage (p?=?.001; p?=?.002), WHO status (0 vs. 1–3; p?=?.003; p?=?.04), and hemoglobin level (<12?g/dl>; p?=?.04; p?=?.02). The 5?year overall survival for stage II of AC and SCC was 63% and 82% (p?=?.03), and for IIIA,B it was 33.6% and 73% (p?=?.0005). The 5?year RFS for AC and SCC stage FIGO IIIA,B was 24% and 57% (p?=?.001).

Conclusions: Adenocarcinoma histology negatively impacts OS and RFS for advanced cervical cancer. Histology-specific therapy may be an opportunity for survival improvement in these women.     

An adjusted indirect comparison of everolimus and sorafenib therapy in sunitinib-refractory metastatic renal cell carcinoma patients using repeated matched samples

Objective: To date, no trial data exist comparing treatment outcomes for everolimus versus sorafenib. The current analysis indirectly compares the overall survival (OS) benefit of everolimus and sorafenib as second-line treatment options.

Research design and methods: A single-arm sorafenib study is selected as a basis to match an everolimus sunitinib-refractory subpopulation of the RECORD-1 trial. Only patients with clear cell histology are included. An adjusted matching approach is taken where 1000 repeated random samples matched to the sorafenib population on risk score distribution are produced, and a 95% CI around the mean of all sampled median OS is generated.

Main outcome measures: The main outcome measures include adjusted median OS and progression-free survival.

Results: In all, 45 clear cell histology sorafenib patients and 1000 samples of N = 41 sunitinib-refractory everolimus patients are considered for analysis. After adjusted matching, the estimated median OS benefit is 32.7 weeks (95% CI: 22, 64) and 81.5 weeks (95% CI: 78, 86) for sorafenib and everolimus patients, respectively.

Conclusion: Results suggest that sunitinib-refractory metastatic renal cell carcinoma patients treated with everolimus may experience significantly improved OS outcomes compared to those treated with sorafenib. However, because this is not a randomized controlled trial, the results should be interpreted as those from an observational study.