A Th1/IFNγ Gene Signature Is Prognostic in the Adjuvant Setting of Resectable High-Risk Melanoma but Not in Non-Small Cell Lung Cancer.

Purpose: Immune components of the tumor microenvironment (TME) have been associated with disease outcome. We prospectively evaluated the association of an immune-related gene signature (GS) with clinical outcome in melanoma and non-small cell lung cancer (NSCLC) tumor samples from two phase III studies.

Experimental Design: The GS was prospectively validated using an adaptive signature design to optimize it for the sample type and technology used in phase III studies.

RECIST 1.1 for Response Evaluation Apply Not Only to Chemotherapy-Treated Patients But Also to Targeted Cancer Agents: A Pooled Database Analysis.

Purpose: The mode of action of targeted cancer agents (TCAs) differs from classic chemotherapy, which leads to concerns about the role of RECIST in evaluating tumor response in trials with TCAs. We investigated the performance of RECIST using a pooled database from 50 clinical trials with at least one TCA.

Methods: We examined the impact of the number of target lesions (TLs) on within-patient variability of tumor response.

The Servier oncology pipeline in 2017.

Cancer is a complex, multifactorial disease that for years has been the focus of intensive research efforts to explore both the molecular and biological mechanisms involved and the development of novel agents to target these pathways. Servier is an independent French pharmaceutical company with a focus on oncology. Currently, Servier's commercial portfolio includes agents used to treat non-Hodgkin's lymphoma and metastatic colorectal cancer; Servier's oncology pipeline involves agents for the treatment of both solid and hematological tumors.

iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics.

Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden-a mainstay of evaluation of cancer therapeutics that provides key information about objective response and disease progression. A consensus guideline-iRECIST-was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline.

RECIST 1.1 - Standardisation and disease-specific adaptations: Perspectives from the RECIST Working Group.

Radiologic imaging of disease sites plays a pivotal role in the management of patients with cancer. Response Evaluation Criteria in Solid Tumours (RECIST), introduced in 2000, and modified in 2009, has become the de facto standard for assessment of response in solid tumours in patients on clinical trials. The RECIST Working Group considers the ability of the global oncology community to implement and adopt updates to RECIST in a timely manner to be critical.

RECIST 1.1-Update and clarification: From the RECIST committee.

The Response Evaluation Criteria in Solid Tumours (RECIST) were developed and published in 2000, based on the original World Health Organisation guidelines first published in 1981. In 2009, revisions were made (RECIST 1.1) incorporating major changes, including a reduction in the number of lesions to be assessed, a new measurement method to classify lymph nodes as pathologic or normal, the clarification of the requirement to confirm a complete response or partial response and new methodologies for more appropriate measurement of disease progression.

Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Fewer than half of the patients with completely resected non-small-cell lung cancer (NSCLC) are cured. Since the introduction of adjuvant chemotherapy in 2004, no substantial progress has been made in adjuvant treatment. We aimed to assess the efficacy of the MAGE-A3 cancer immunotherapeutic in surgically resected NSCLC.

Rates of MAGE-A3 and PRAME expressing tumors in FFPE tissue specimens from bladder cancer patients: potential targets for antigen-specific cancer immunotherapeutics.

Introduction: Antigen-specific active immunotherapy is an investigational therapeutic approach of potential interest for bladder cancer regardless of disease stage. Clinical development of antigen-specific immunotherapeutics against bladder cancer must be preceded by assessment of the expression of relevant genes in bladder tumors. The objectives of this study (NCT01706185) were to assess the rate of expression of the MAGE-A3 and PRAME genes in bladder tumors and to investigate the feasibility of using formalin-fixed paraffin-embedded (FFPE) tumor tissues for testing.

Recommendations for capture, validation and summarisation of data from studies using RECIST.

Response Evaluation Criteria in Solid Tumors (RECIST) is commonly used in oncology clinical trials and provides a standard approach for the assessment of treatment. However, data capture, validation and summarisation are complex. This article focuses on managing solid tumour lesion and response assessment data from capture through summarisation.

Pattern of care in locally advanced breast cancer: focus on local therapy.

Background And Methods: The optimal treatment of locally advanced breast cancer (LABC) remains undetermined. We analyzed factors influencing local therapy in LABC in a pooled material including three large clinical series.

Results: Of a total of 787 patients, local therapy was given in 604, surgery in 184, radiotherapy in 69, and a combination thereof in 351.

Improving cancer outcomes through international collaboration in academic cancer treatment trials.

Purpose: The need for international collaboration in cancer clinical trials has grown stronger as we have made progress both in cancer treatment and screening. We sought to identify those efforts already underway which facilitate such collaboration, as well as barriers to greater collaboration.

Methods: We reviewed the collective experiences of many cooperative groups, governmental organizations, nongovernmental organizations, and academic investigators in their work to build international collaboration in cancer clinical trials across multiple disease sites.

Individual patient data analysis to assess modifications to the RECIST criteria.

Background: After the initial RECIST 1.0 were published in 2000, the criteria were widely implemented in the scientific oncology community. Since then, the RECIST working group has identified several issues to examine further.

Cancer clinical trial outcomes: any progress in tumour-size assessment?

Cancer for many patients is still a lethal disease, and we are at the edge of the time that it will be the leading cause of death in the western world. One of the hallmarks of cancer is its ability to spread to other organs, turning cancer in essence to a systemic disease. For this reason, systemic therapy plays an important role in our efforts to either obtain cure or to prolong life and palliate symptoms.

Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group.

Purpose: This phase III randomized open-label clinical trial was designed to evaluate the efficacy and safety of the steroidal aromatase inactivator exemestane versus the antiestrogen tamoxifen as first-line treatment for metastatic breast cancer (MBC) in postmenopausal women.

Patients And Methods: The study was conducted at 81 centers and enrolled postmenopausal patients with measurable hormone-sensitive metastatic or locally advanced breast cancer. Prior adjuvant chemotherapy and/or tamoxifen were allowed.

Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer.

Purpose: Overall survival (OS) can be observed only after prolonged follow-up, and any potential effect of first-line therapies on OS may be confounded by the effects of subsequent therapy. We investigated whether tumor response, disease control, progression-free survival (PFS), or time to progression (TTP) could be considered a valid surrogate for OS to assess the benefits of first-line therapies for patients with metastatic breast cancer.

Patients And Methods: Individual patient data were collected on 3,953 patients in 11 randomized trials that compared an anthracycline (alone or in combination) with a taxane (alone or in combination with an anthracycline).

Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer.

Purpose: Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival.

Patients And Methods: Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines.

Magnetic resonance imaging of the axial skeleton for detecting bone metastases in patients with high-risk prostate cancer: diagnostic and cost-effectiveness and comparison with current detection strategies.

Purpose: To evaluate the diagnostic performance, costs, and impact on therapy of one-step magnetic resonance imaging (MRI) of the axial skeleton (MRIas) for detecting bone metastases in patients with high-risk prostate cancer (PCa).

Patients And Methods: Sixty-six consecutive patients with high-risk PCa prospectively underwent MRIas in addition to the standard sequential work-up (SW) of bone metastases (technetium-99m bone scintigraphy [BS] completed with targeted x-rays [TXR] in patients with equivocal BS findings and with MRI obtained on request [MRIor] in patients with inconclusive BS/TXR findings). Panel review of initial and 6-month follow-up MRI findings, BS/TXR, and all available baseline and follow-up clinical and biologic data were used as the best valuable comparator to define metastatic status.

Postoperative adjuvant chemotherapy followed by adjuvant tamoxifen versus nil for patients with operable breast cancer: a randomised phase III trial of the European Organisation for Research and Treatment of Cancer Breast Group.

Background: The contribution of adjuvant tamoxifen in breast cancer patients after receiving adjuvant chemotherapy is not fully established. We investigated the impact of tamoxifen, given sequentially after completion of adjuvant chemotherapy in patients with operable breast cancer.

Patients And Methods: Between March 1991 and June 1999, 1863 women with stages I-IIIA operable breast cancer who had undergone surgery and completed six cycles of adjuvant combination chemotherapy with either CMF, CAF, CEF, FAC or FEC were randomised to receive either tamoxifen 20 mg daily for 3 years or no further treatment.

A joined analysis of two European Organization for the Research and Treatment of Cancer (EORTC) studies to evaluate the role of pegylated liposomal doxorubicin (Caelyx) in the treatment of elderly patients with metastatic breast cancer.

We have performed a retrospective analysis to evaluate the impact of age, using a 70 year cutoff, on the safety and efficacy of pegylated liposomal doxorubicin (Caelyx) given at 60 mg/m(2) every 6 weeks (treatment A) or 50 mg/m(2) every 4 weeks (treatment B) to 136 metastatic breast cancer patients in two EORTC trials, of whom 65 were 70 years of age or older. No difference in terms of toxicity was observed between younger and older patients treated with the 4-week schedule, while a higher incidence of hematological toxicity, anorexia, asthenia, and stomatitis was observed in older patients when the 6-week schedule was used. Antitumor activity was not affected by age.

Gene signature evaluation as a prognostic tool: challenges in the design of the MINDACT trial.

This Review describes the work conducted by the TRANSBIG consortium in the development of the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial. The goal of the trial is to provide definitive evidence regarding the clinical relevance of the 70-gene prognosis signature, and to assess the performance of this signature compared with that of traditional prognostic indicators for assigning adjuvant chemotherapy to patients with node-negative breast cancer. We outline the background work and the key questions in node-negative early-stage breast cancer, and then focus on the MINDACT trial design and statistical considerations.

Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer.

Background: A 70-gene signature was previously shown to have prognostic value in patients with node-negative breast cancer. Our goal was to validate the signature in an independent group of patients.

Methods: Patients (n = 307, with 137 events after a median follow-up of 13.

Heterogeneity in disease free survival between centers: lessons learned from an EORTC breast cancer trial.

Background: Large phase III clinical trials convey a lot of important information besides the main analysis of the treatment effect. For example, the use of multicenter clinical trial data to identify prognostic indices is now common. In addition, the study of heterogeneity in patient outcome between centers has received considerable attention in recent years.