Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review

<div><p>Background</p><p>Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal.</p><p><i>Objective</i> The present study aims at estimating the quality of reporting in published oncology phase II clinical trials.</p><p>Data sources</p><p>A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010–2015).</p><p>Study eligibility criteria</p><p>All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer.</p><p>Intervention</p><p>Quality of reporting was assessed using the Key Methodological Score.</p><p>Results</p><p>557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001).</p><p>Limitations</p><p><i>S</i>creening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate.</p><p>Conclusions & implications of key findings</p><p>This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles.</p></div

Factors associated with Key Methodological Score value: Multivariate analysis results.

<p>Factors associated with Key Methodological Score value: Multivariate analysis results.</p

Details of rate of reporting of each item of Key Methodological Score.

<p>Details of rate of reporting of each item of Key Methodological Score.</p

Flowchart.

<p>—Flowchart summarizing the selection process of the phase II trials for analysis (AOO: <i>Annals of Oncology</i>; BJC: <i>British Journal of Cancer</i>; JCO: <i>Journal of Clinical Oncology)</i>.</p

Characteristics of phase II and II/III trials published in the 3 journals selected (N = 557).

<p>Characteristics of phase II and II/III trials published in the 3 journals selected (N = 557).</p

Safety assessment of anticancer drugs in association with radiotherapy in metastatic malignant melanoma: a real-life report

International audiencePurpose To assess the safety of the association of radiotherapy (RT) and systemic treatments for patients with metastatic malignant melanoma (mMM). Methods A retrospective analysis included consecutive patients treated with palliative RT, and at least one line of systemic therapy for mMM between 2001 and 2016. Treatments were defined as sequential or concomitant when RT and the systemic drug were administered, respectively, at more or less than five half-lives from each other. Results 92 patients were included. They had 110 palliative RT treatments. RT was delivered with a “conventional” chemotherapy (mainly fotemustine and/or dacarbazine) and a “modern” systemic therapy (BRAF inhibitors, association of BRAF and MEK inhibitors, immunotherapy), respectively, in 88 (80%) and 22 (20%) cases. Systemic treatments and RT were mainly concurrently performed (n = 61, 55.5%). Regarding acute grade ≥ 3 toxicity, no difference was reported between sequential and concomitant groups either in the whole cohort (p = 1) or in the subgroup of patients receiving “modern” systemic therapies (p = 1). Acute and late grade ≥ 3 toxicities only occurred with vemurafenib. BRAF inhibitors and RT produced more severe infield adverse events than other associations (p = 0.001) with two deaths. Conclusion In our series, compared to sequential administration, concomitant association of systemic anticancer drugs and palliative RT did not increase toxicity in mMM patients. BRAF inhibitors and RT produced severe infield toxicities. Prospective studies are needed to better characterize the toxicity of each association

Local treatment in the setting of de novo metastatic rectal cancer: reappraisal of prognostic factors

BACKGROUND: This retrospective study was conducted to: (1) provide more modern data on real-life local management of metastatic rectal cancer; (2) compare therapeutic strategies; and (3) identify prognostic factors of local failure, overall survival and progression-free survival. METHODS: Data about efficacy and acute toxicity were collected. Patients were diagnosed with metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. Local failure, overall survival and progression-free survival were correlated with patient, tumour and treatment characteristics using univariate and multivariate analyses. RESULTS: Data of 148 consecutive patients with metastatic rectal cancer were analysed. Median follow-up was 19 months. Median overall survival was 16 months. All patients received local radiotherapy, with a median equivalent 2 Gy per fraction dose of 47.7 Gy. Rectal surgery was performed in 97 patients (65.6%). The majority of patients (86/97, 88.7%) received pre-operative chemoradiation. In multivariate analysis, rectal surgery was found to be the only independent predictor of increased overall survival (24.6 vs 7.1 months, p <0.001). Of the patients undergoing surgical treatment, 22.8% presented with significant complications that required a delay of systemic treatment. Grade 3–4 acute radiation therapy-related toxicities were observed in 6.1% of patients, mainly gastrointestinal toxicities (5.4%). CONCLUSION: Rectal surgery was a key predictive factor of increased progression-free survival and overall survival in patients receiving at least local radiotherapy. In our series of real-life patients, local surgery and radiation seemed as well tolerated as reported in selected phase III non-metastatic rectal cancer patients. These data suggested that local management could be beneficial for metastatic rectal cancer patients