Abiraterone in patients with recurrent epithelial ovarian cancer: principal results of the phase II Cancer of the Ovary Abiraterone (CORAL) trial (CRUK - A16037).

BACKGROUND: Recurrent epithelial ovarian cancer (EOC) remains difficult to treat, with an urgent need for more therapy options. Androgens bind to the androgen receptor (AR), commonly expressed in EOC. CYP17 inhibitor abiraterone irreversibly inhibits androgen biosynthesis. The Cancer of the Ovary Abiraterone (CORAL) trial was designed to evaluate the clinical activity of abiraterone in EOC. PATIENTS & METHODS: CORAL was a multi-centre, open-label, non-randomised, 2-stage phase II clinical trial. Eligible patients had progression within 12 months of last systemic therapy and no prior hormonal anti-cancer agents. Patients received abiraterone 1000 mg daily plus 5 mg prednisone until progression. The primary endpoint was objective response rate (ORR) according to combined Response Evaluation Criteria in Solid Tumours/Gynaecological Cancer Intergroup (RECIST/GCIG) criteria at 12 weeks. Secondary endpoints included clinical benefit rate (CBR) at 12 weeks. RESULTS: A total of 42 patients were recruited; median age 65 (range 34-85) years; 37 (88.1%) had high-grade serous tumours; 20 (48%) had at least three prior lines of therapy; 29/40 (72.5%) were AR+. In stage 1, 1/26 response was observed (in an AR+, low-grade serous EOC); response lasted 47 weeks. Overall, 12 week ORR was 1/42 (2%), CBR was 11/42 (26%) (8/29 (28%) in AR+ patients). Disease control was ⩾6 months for 4/29 (14%). One patient (AR+, low-grade serous) had a RECIST response at 82 weeks. Four (10%) had grade ⩾3 hypokalaemia; 11 (26%) had dose delays. CONCLUSIONS: CORAL represents the first trial of an AR targeted agent in ovarian cancer. While responses were rare, a subset of patients achieved sustained clinical benefit. Targeting AR in EOC including low-grade serous cancer warrants further investigation. TRIAL REGISTRATION: CORAL is registered on the ISRCTN registry: ISRCTN63407050; http://www.isrctn.com/ISRCTN63407050.

Targeted agents and combinations in ovarian cancer: where are we now?

Epithelial ovarian cancer is a heterogeneous disease with distinct histological subtypes characterized by different patterns of clinical behaviour. The identification of molecular pathways associated with individual subtypes has fuelled enthusiasm for the development of targeted therapies directed at specific subtypes of ovarian cancer. To date, the most successful targeted therapies in ovarian cancer to have undergone clinical development include anti-angiogenic agents and PARP inhibitors. Other promising areas of development include folate receptor antagonists, MEK and BRAF inhibitors in low-grade serous carcinoma, and immunotherapy. These novel therapeutic agents have the potential to maximize tumor efficacy, minimize toxicity and improve outcomes for women with epithelial ovarian cancer.

VEGF-A levels in bevacizumab-treated breast cancer patients: a systematic review and meta-analysis.

Bevacizumab may improve outcomes of patients with breast cancer, but the absence of an established biomarker hampers patient selection and researchers´ ability to demonstrate a clear survival benefit. Its putative target, circulating VEGF-A, emerged as the main candidate and we sought to identify the relationship between VEGF-A levels and outcomes through systematic review. We searched electronic databases and meeting proceedings for randomized controlled trials (RCTs) comparing the addition of bevacizumab to standard chemotherapy for breast cancer. RCTs were included if outcomes were presented separately according to VEGF-A plasma levels. Random-effects model were applied to calculate the pooled hazard ratios for progression-free survival, event-free survival (EFS), comprising disease recurrence, progression or any-cause death, and overall survival (OS), with respective confidence intervals (95 % CI). High and low VEGF-A levels subgroups followed each trial definition, and results were compared using the interaction test. Heterogeneity was calculated using χ (2) test (I (2)). Three trials enrolled a total of 3748 patients. 1713 patients had baseline VEGF-A levels in plasma available for assessment and were included. One trial added bevacizumab in the adjuvant setting (N = 2591) and two on first-line metastatic disease with taxane-based therapy (N = 1160) There was no interaction between VEGF-A levels and study setting (adjuvant vs. first line therapy). Bevacizumab improved PFS of patients with above median VEGF-A plasma levels (HR 0.56; 95 % CI 0.43-0.73; P < 0.001; I (2) = 0 %), but not of those with below median VEGF-A levels (HR 0.89; 95 % CI 0.68-1.15; P = 0.37; I (2) = 0 %), with relevant differences between these two groups, P-for interaction = 0.02. The same happened with EFS (VEGF-A above median HR 0.62; 95 % CI 0.39-0.79; P < 0.001; I (2) = 11 %; below median HR 0.89; 95 % CI 0.71-1.14; P = 0.98; I (2) = 17 %; P-for interaction = 0.03). OS data were not available. VEGF-A level is a reasonable candidate biomarker for bevacizumab in the treatment of breast cancer. Further studies have to confirm its surrogacy in overall survival and in other scenarios including other anti-angiogenic therapies.

Is there a role for consolidative radiotherapy in the treatment of aggressive and localized non-Hodgkin lymphoma? A systematic review with meta-analysis.

BACKGROUND: Chemotherapy is the mainstay of non-Hodgkin lymphoma (NHL) treatment. Based on expert opinion, the use of radiotherapy (RT) is currently preferred in some institutions as consolidative treatment for patients with localized disease. The lack of conclusive data coming from conflicting studies about the impact of treatment demands a systematic review, which could provide the most reliable assessment for clinical decision-making. We evaluate the addition of RT post-CT, for aggressive and localized NHL (ALNHL). METHODS: Randomized controlled trials (RCT) that evaluated chemotherapy alone versus chemotherapy plus RT were searched in databases. The outcomes were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity. Risk ratio (RR) and hazard ratio (HR) with their respective 95% confidence intervals (CI) were calculated using a fized-effect model. RESULTS: Four trials (1,796 patients) met the inclusion criteria. All trials tested the use of RT after systemic therapy comprising anthracycline-based chemotherapy. This systematic review showed that RT enhances PFS after chemotherapy (hazard ratio [HR] 0.81; 95% CI 0.67-0.98; p = 0.03), with no impact on ORR and OS. Some heterogeneity between trials could limit the conclusions about OS. Toxicity data could not be pooled due to differences in reporting adverse events. CONCLUSIONS: This systematic review with meta-analysis shows no improvement in survival when adding RT to systemic therapy for ALNHL. Our conclusions are limited by the available data. Further evaluations of new RT technologies and its association with biologic agents are needed.

Articles with short titles describing the results are cited more often.

OBJECTIVE: The aim of this study was to evaluate some features of article titles from open access journals and to assess the possible impact of these titles on predicting the number of article views and citations. METHODS: Research articles (n = 423, published in October 2008) from all Public Library of Science (PLoS) journals and from 12 Biomed Central (BMC) journals were evaluated. Publication metrics (views and citations) were analyzed in December 2011. The titles were classified according to their contents, namely methods-describing titles and results-describing titles. The number of title characters, title typology, the use of a question mark, reference to a specific geographical region, and the use of a colon or a hyphen separating different ideas within a sentence were analyzed to identify predictors of views and citations. A logistic regression model was used to identify independent title characteristics that could predict citation rates. RESULTS: Short-titled articles had higher viewing and citation rates than those with longer titles. Titles containing a question mark, containing a reference to a specific geographical region, and that used a colon or a hyphen were associated with a lower number of citations. Articles with results-describing titles were cited more often than those with methods-describing titles. After multivariate analysis, only a low number of characters and title typology remained as predictors of the number of citations. CONCLUSIONS: Some features of article titles can help predict the number of article views and citation counts. Short titles presenting results or conclusions were independently associated with higher citation counts. The findings presented here could be used by authors, reviewers, and editors to maximize the impact of articles in the scientific community.

Independent radiologic review in metastatic colorectal cancer: systematic review and meta-analysis.

PURPOSE: To perform a meta-analysis addressing evaluation bias in local radiologic assessment (LRA) of lesions when compared with independent radiologic review (IRR) in randomized controlled trials (RCTs) testing chemotherapy for metastatic colorectal cancer (CRC). MATERIALS AND METHODS: MEDLINE, EMBASE, ClinicalTrials.gov, the Cochrane Library, and Web sites for major medical meetings were searched for RCTs of chemotherapy for metastatic CRC that reported response evaluation by both LRA and IRR. The risk ratios (RRs) of response in the experimental (RR(exp)) and control (RR(cont)) arms were calculated (response rate in LRA divided by response rate in IRR) for each selected study. The ratio of RR of response was calculated (RR of response of LRA divided by RR of response of IRR). The random-effects model was applied. Meta-regression was used to examine the effect of study characteristics on outcomes. RESULTS: LRA and IRR results were concordant (13 studies; 7742 patients; ratio of RR of response = 0.97; 95% confidence interval [95% CI]: 0.90, 1.04; P = .35). However, LRA overestimated tumor response independently of therapy allocation (interaction test, P = .81) both in control (RR(cont), 1.163; 95% CI: 1.086, 1.246; P < .001) and experimental (RR(exp), 1.156; 95% CI: 1.093, 1.222; P < .001) therapies. Meta-regression did not show any effect of trial characteristics on effects. CONCLUSION: LRA yields higher response rates in RCTs testing chemotherapy for metastatic CRC, although there was no sign of bias toward experimental therapy. The need for IRR to control evaluation bias must be reappraised.

Articles with short titles describing the results are cited more often

OBJECTIVE: The aim of this study was to evaluate some features of article titles from open access journals and to assess the possible impact of these titles on predicting the number of article views and citations. METHODS: Research articles (n = 423, published in October 2008) from all Public Library of Science (PLoS) journals and from 12 Biomed Central (BMC) journals were evaluated. Publication metrics (views and citations) were analyzed in December 2011. The titles were classified according to their contents, namely methods-describing titles and results-describing titles. The number of title characters, title typology, the use of a question mark, reference to a specific geographical region, and the use of a colon or a hyphen separating different ideas within a sentence were analyzed to identify predictors of views and citations. A logistic regression model was used to identify independent title characteristics that could predict citation rates. RESULTS: Short-titled articles had higher viewing and citation rates than those with longer titles. Titles containing a question mark, containing a reference to a specific geographical region, and that used a colon or a hyphen were associated with a lower number of citations. Articles with results-describing titles were cited more often than those with methods-describing titles. After multivariate analysis, only a low number of characters and title typology remained as predictors of the number of citations. CONCLUSIONS: Some features of article titles can help predict the number of article views and citation counts. Short titles presenting results or conclusions were independently associated with higher citation counts. The findings presented here could be used by authors, reviewers, and editors to maximize the impact of articles in the scientific community.

Optimal duration of first-line chemotherapy for advanced non-small cell lung cancer: a systematic review with meta-analysis.

BACKGROUND: The optimal duration of first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) has been a matter for debate for nearly 20 years. In order to elucidate this issue, a meta-analysis comparing the different durations of same treatments was performed. METHODS: We searched for all published randomised controlled trials (RCTs) comparing different durations of first-line treatment of advanced NSCLC. The MEDLINE, EMBASE, LILACS and CENTRAL databases were searched for RCTs comparing a defined number of cycles of chemotherapy versus continuing treatment until disease progression, or a defined number of cycles versus a higher number of cycles of the same chemotherapy. Trials including biological agents were excluded. RESULTS: Seven trials that included 1559 patients were analysed. Treatment for more than 4 cycles was associated with a non-statistically significant decrease in the hazard of mortality relative to shorter treatment (hazard ratio (HR)=0.97; 95% confidence interval (CI)=0.84-1.11; P=.65). In those treated with third-generation chemotherapy through the whole study time, treatment for more than 4 cycles was associated with a non-statistically significant increase in mortality (HR=1.08; 95% CI=0.90-1.28; P=.28). Patients receiving more chemotherapy had significant longer progression-free survival (HR=.75; 95% CI=0.60-0.85; P<0.0001) than the group with shorter duration of treatment. In an intent-to-treat analysis, there was no difference in the overall response rate between the groups (odds ratio (OR)=0.78; 95% CI=0.60-1.01; P=.96). Longer treatment was associated with more severe leucopaenia but with no significant increase in non-haematological toxicities. CONCLUSIONS: In patients with advanced NSCLC the use of more than 4 cycles of first-line chemotherapy with third-generation regimens significantly increases progression-free survival but not overall survival and is associated with higher incidence of adverse events. There is no evidence to support continuous chemotherapy until progression in patients with lung cancer.