Validity and Efficiency of Progression-Free Survival-2 as a Surrogate End Point for Overall Survival in Advanced Cancer Randomized Trials.

Purpose: Progression-free survival (PFS)-2, defined as the time from randomization to progression on second-line therapy, is potentially a more reliable surrogate than PFS for overall survival (OS), but will require longer follow-up and a larger sample size. We sought to compare the validity and efficiency, defined as proportional increase in follow-up time and sample size, of PFS-2 to PFS.

Methods: We performed an electronic search to identify randomized trials of advanced solid tumors reporting PFS, PFS-2, and OS as prespecified end points.

Dedifferentiated umbilical metastases from low grade endometrioid endometrial adenocarcinoma complicated by super-obesity: A case report.

Introduction: Umbilical metastases are uncommon and rarely associated with endometrial cancer. In this report we describe a unique case of a patient with low-grade endometrioid adenocarcinoma (EAC) who developed an umbilical metastasis containing dedifferentiated endometrial carcinoma, in the context of super-morbid obesity with a body mass index (BMI) of 80 kg/m.

Presentation Of Case: A 55-year-old female with atypical endometrial hyperplasia was treated with progestogens whilst attempting weight loss prior to definitive surgery, given the impact of her obesity on surgical risk.

Results of PD-L1 Analysis of Women Treated with Durvalumab in Advanced Endometrial Carcinoma (PHAEDRA).

Women with advanced endometrial carcinoma (EC) with mismatch repair (MMR) deficiency have improved outcomes when treated with immune checkpoint inhibitors; however, additional biomarkers are needed to identify women most likely to respond. Scores for programmed death ligand 1 (PD-L1), immunohistochemical staining of tumor (TC+), immune cells (IC+) and presence of tumor-associated immune cells (ICP) on MMR deficient (n = 34) and proficient (n = 33) EC from women treated with durvalumab in the PHAEDRA trial (ANZGOG1601/CTC0144) (trial registration number ACTRN12617000106336, prospectively registered 19 January 2017) are reported and correlated with outcome. Receiver operating characteristic (ROC) analyses and area under the ROC curve were used to determine optimal cutpoints.

Outcomes of extensive stage extrapulmonary small cell cancer.

Background: Extrapulmonary small cell cancer (EPSCC) is a rare malignancy with an incidence of approximately 0.1%-0.4% of all cancers.

Pre- and on-treatment lactate dehydrogenase as a prognostic and predictive biomarker in advanced non-small cell lung cancer.

Background: The survival outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are variable. This study investigated whether pre- and on-treatment lactate dehydrogenase (LDH) could better prognosticate and select patients for ICI therapy.

Methods: Using data from the POPLAR and OAK trials of atezolizumab versus docetaxel in previously treated advanced NSCLC, the authors assessed the prognostic and predictive value of pretreatment LDH (less than or equal to vs greater than the upper limit of normal).

Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trial.

Introduction: There is a strong theoretical rationale for combining checkpoint blockade with cytotoxic chemotherapy in pleural mesothelioma and other cancers. Two recent single-arm, phase 2 trials [DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (PrE0505)] combining the programmed death ligand-1 (PD-L1) inhibitor durvalumab with standard first-line chemotherapy exceeded prespecified safety and activity criteria to proceed to a phase 3 confirmatory trial to assess this combination. We present the protocol of the DREAM3R trial.

The validity of progression-free survival 2 as a surrogate trial end point for overall survival.

Background: Overall survival (OS) is the gold-standard end point for oncology trials. However, the availability of multiple therapeutic options after progression and crossover to receive investigational agents confound and delay OS data maturation. Progression-free survival 2 (PFS-2), defined as the time from randomization to progression on first subsequent therapy, has been proposed as a surrogate for OS.

Incorporating circulating tumor DNA detection to radiographic assessment for treatment response in advanced EGFR-mutant lung cancer.

Purpose: Response Evaluation Criteria in Solid Tumors (RECIST) has limitations but remains the conventional approach for tumor assessments. We explored whether circulating tumor DNA (ctDNA) can be incorporated into RECIST to provide a more robust measure of tumor response in advanced EGFR-mutant NSCLC.

Patients And Methods: In FASTACT-2, patients with advanced NSCLC received platinum/gemcitabine intercalated with erlotinib or placebo.

Tumor Response End Points as Surrogates for Overall Survival in Immune Checkpoint Inhibitor Trials: A Systematic Review and Meta-Analysis.

Purpose: Many immune checkpoint inhibitors (ICIs) have been approved on the basis of tumor response end points in nonrandomized trials, including objective response rate (ORR) and duration and depth of response. We aimed to assess the validity of these end points as surrogate end points for overall survival (OS) in patients with advanced solid tumors treated with ICIs at trial and treatment arm levels.

Methods: ICI trials in advanced solid cancers published between January 1, 2000, and March 31, 2020, were included.

Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial.

Background: In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC)-mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR).

Methods: A multicenter phase two study was performed in women with AEC with pMMR tumor progressing after one to three lines of chemotherapy and women with AEC with dMMR tumor progressing after zero to three lines of chemotherapy. Mismatch repair status was based on immunohistochemistry expression.

Clinical utility of plasma EGFR mutation detection with quantitative PCR in advanced lung cancer: A meta-analysis.

Objectives: To assess the clinical utility of quantitative PCR (qPCR) assays, a routinely used test for detection of epidermal growth factor receptor (EGFR) mutation in circulating tumour DNA (ctDNA) in treatment-naive advanced lung cancer patients.

Materials And Methods: We performed a meta-analysis of randomized controlled trials (RCTs) with individual patient data. Eligible RCTs compared EGFR-tyrosine kinase inhibitor (EGFR-TKI) and chemotherapy in first line setting for advanced lung cancer, and included tumour EGFR+ (tEGFR+) with paired ctDNA results using real-time (quantitative) PCR.

Validation of Progression-Free Survival Rate at 6 Months and Objective Response for Estimating Overall Survival in Immune Checkpoint Inhibitor Trials: A Systematic Review and Meta-analysis.

Importance: Progression-free survival (PFS) rate at 6 months has been proposed as a potential surrogate for overall survival (OS) rate at 12 months for immune checkpoint inhibitor (ICI) trials but requires further assessment for validation.

Objective: To validate 6-month PFS and objective response rate (ORR) as estimators of 12-month OS in the ICI arms of randomized clinical trials (RCTs).

Data Sources: Electronic databases (Medline, EMBASE, and the Cochrane Central Register of Controlled Trials) were searched for ICI RCTs published between January 2000 and June 2019.

Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in.

Background: There is a strong unmet need to improve systemic therapy in mesothelioma. Chemotherapy with cisplatin and pemetrexed improves survival in malignant pleural mesothelioma, and immune checkpoint inhibitors are an emerging treatment in this disease. We aimed to evaluate the activity of durvalumab, an anti-PD-L1 antibody, given during and after first-line chemotherapy with cisplatin and pemetrexed in patients with advanced malignant pleural mesothelioma.

PARAGON (ANZGOG-0903): a phase 2 study of anastrozole in asymptomatic patients with estrogen and progesterone receptor-positive recurrent ovarian cancer and CA125 progression.

Objective: A subset of patients with recurrent ovarian cancer (ROC) may benefit from antiestrogen therapy with higher response rates reported in tumors that are strongly estrogen receptor (ER)-positive (ER⁺). PARAGON is a basket trial that incorporates 7 phase 2 trials investigating the activity of anastrozole in patients with ER⁺ and/or progesterone receptor (PR)-positive (PR⁺) recurrent/metastatic gynecological cancers.

Methods: Postmenopausal women with ER⁺ and/or PR⁺ ROC, who were asymptomatic and had cancer antigen 125 (CA125) progression after response to first line chemotherapy, where chemotherapy was not clinically indicated.

Evaluating the addition of oxaliplatin to single agent fluoropyrimidine in the treatment of locally advanced rectal cancer: a systematic review and meta-analysis.

Introduction: Multimodality treatment of patients with locally advanced rectal cancer (LARC) has significantly improved local disease control, however the unaltered overall survival (OS) implicates an inability to further control micrometastases, providing rationale for intensified systemic treatment. A systematic review was conducted to evaluate the efficacy and toxicity of adding oxaliplatin to a fluoropyrimidine (intervention) compared with fluoropyrimidine alone (control) in the treatment of LARC.

Methods: We searched CENTRAL, Medline Ovid, PubMed and EMBASE databases.

Enhanced Recovery After Surgery for Suspected Ovarian Malignancy: A Survey of Perioperative Practice Among Gynecologic Oncologists in Australia and New Zealand to Inform a Clinical Trial.

Objectives: The objective of this survey was to review the current standard of perioperative care of patients with suspected advanced ovarian cancer in Australia and New Zealand in order to determine the level of equipoise for specific interventions.

Methods: In May 2016, a web-based questionnaire (SurveyMonkey Inc, Palo Alto, CA) was sent to all gynecologic oncologists in Australia and New Zealand (n = 56). Descriptive statistics were used.

Enhanced Recovery After Surgery for Advanced Ovarian Cancer: A Systematic Review of Interventions Trialed.

Objectives: We sought to summarize the evidence for interventions aiming at enhanced recovery after surgery (ERAS) in ovarian cancer through a systematic review.

Methods: We searched MEDLINE, EMBASE, and The Cochrane Library for studies testing ERAS interventions in patients undergoing surgery for ovarian cancer. Study selection and data extraction were done independently by 2 reviewers with disagreements resolved by discussion with a senior, third reviewer.

A systematic evaluation of compliance and reporting of patient-reported outcome endpoints in ovarian cancer randomised controlled trials: implications for generalisability and clinical practice.

Background: This study aimed to evaluate the patient-reported outcome (PRO) content of ovarian cancer randomised-controlled trial (RCT) publications, describe PRO compliance, and explore potential relationships among these and completeness of PRO protocol content.

Methods: Publications of Phase III ovarian cancer RCTs with PRO endpoints were identified by Medline and Cochrane systematic search: January 2000 to February 2016. Two reviewers determined the number of Consolidated Standards of Reporting Trials (CONSORT)-PRO Extension items addressed in publications.

The patient-reported outcome content of international ovarian cancer randomised controlled trial protocols.

Purpose: Patient-reported outcomes (PROs) provide the patient's perspective of the impact of treatment. Evidence suggests that PRO content of randomised controlled trials (RCTs) protocols is generally sub-optimal. This study aimed to describe and evaluate the PRO-specific content of ovarian cancer RCT protocols.