Nivolumab in gastric/gastroesophageal junction cancer: real-world data from UK Early Access to Medicines Scheme.

Aim: This study provides real-world insight into patient profile, clinical effectiveness and health-related quality of life among patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma treated with nivolumab. Materials & methods: Data were collected from medical records of patients with advanced GEJ adenocarcinoma treated with nivolumab in a UK Early Access to Medicines Scheme and from the patient-reported EuroQoL five dimensions questionnaire. Results: Evaluable patients (n = 113; median age 62 years) were predominantly male (76.1%), White (87.4%) and with GEJ adenocarcinoma (61.9%). Median follow-up was 2.8 months. The 6-month progression-free survival and overall survival were 31.6 and 56.7%, respectively. Mean EuroQoL five dimensions questionnaire index utility scores at baseline, 8, 16 and 24 weeks were 0.795, 0.831, 0.870 and 0.793, respectively. Conclusion: Progression-free survival was consistent with trial results and health-related quality of life remained stable over time.

Lay abstract This study looked at the characteristics and quality of life (QoL) of patients who were taking the drug, nivolumab, and how well it works for advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. GEJ adenocarcinoma is a rare type of cancer that starts in the GEJ, the area where the esophagus and stomach join. Information was collected from the medical records of patients who had advanced GEJ adenocarcinoma and were treated with nivolumab as part of a UK program that gives people access to new treatments that are not yet licensed. Patients also filled out a questionnaire called the EuroQoL five dimensions questionnaire that focuses on a patient's quality of life (QoL). In total, 113 patients were a part of the study. The midpoint of all patients' ages was 62 years and they were mostly males (76.1%), Whites (87.4%) and with GEJ adenocarcinoma (61.9%). The midpoint of follow-up time was 2.8 months. The percentages of patients meeting progression-free survival for 6 months, a period when a patient lives with GEJ adenocarcinoma but it does not get worse, and overall survival were 31.6 and 56.7%, respectively. Mean EuroQoL five dimensions questionnaire index scores (comprised between zero and one, the higher the better) at treatment start, 8, 16 and 24 weeks were 0.795, 0.831, 0.870 and 0.793, respectively. Progression-free survival was similar to clinical trial results and QoL was constant over time.

Vedolizumab and Anti-Tumour Necrosis Factor α Real-World Outcomes in Biologic-Naïve Inflammatory Bowel Disease Patients: Results from the EVOLVE Study.

BACKGROUND AND AIMS: This study aimed to compare real-world clinical effectiveness and safety of vedolizumab, an α4ß7-integrin inhibitor, and anti-tumour necrosis factor-α [anti-TNFα] agents in biologic-naïve ulcerative colitis [UC] and Crohn's disease [CD] patients. METHODS: This was a 24-month retrospective medical chart study in adult UC and CD patients treated with vedolizumab or anti-TNFα in Canada, Greece and the USA. Inverse probability weighting was used to account for differences between groups. Primary outcomes were cumulative rates of clinical effectiveness [clinical response, clinical remission, mucosal healing] and incidence rates of serious adverse events [SAEs] and serious infections [SIs]. Secondary outcomes included cumulative rates of treatment persistence [patients who did not discontinue index treatment during follow-up] and dose escalation and incidence rates of disease exacerbations and disease-related surgeries. Adjusted analyses were performed using inverse probability weighting. RESULTS: A total of 1095 patients [604 UC, 491 CD] were included. By 24 months, rates of clinical effectiveness were similar between groups, but incidence rates of SAEs (hazard ratio [HR] = 0.42 [0.28-0.62]) and SIs (HR = 0.40 [0.19-0.85]) were significantly lower in vedolizumab vs anti-TNFα patients. Rates of treatment persistence [p < 0.01] by 24 months were higher in vedolizumab patients with UC. Incidence rates of disease exacerbations were lower in vedolizumab patients with UC (HR = 0.58 [0.45-0.76]). Other outcomes did not significantly differ between groups. CONCLUSION: In this real-world setting, first-line biologic therapy in biologic-naïve patients with UC and CD demonstrated that vedolizumab and anti-TNFα treatments were equally effective at controlling disease symptoms, but vedolizumab has a more favourable safety profile.

Real-world clinical effectiveness and safety of vedolizumab and anti-tumor necrosis factor alpha treatment in ulcerative colitis and Crohn's disease patients: a German retrospective chart review.

BACKGROUND: Real-world comparisons of biologic treatment outcomes for ulcerative colitis (UC) or Crohn's disease (CD) patients are limited. We sought to evaluate the real-world effectiveness of vedolizumab (VDZ) and anti-tumor necrosis factor alpha (anti-TNFα) in UC and CD patients in Germany. METHODS: A retrospective chart review (15 sites) investigated UC and CD patients who were biologic-treatment naïve (biologic-naïve) or had received no more than one prior anti-TNFα before initiating treatment with VDZ or anti-TNFα between 15 July 2014 and 20 October 2015. Kaplan-Meier analyses assessed time to first chart-documented clinical remission (CR) and symptom resolution (UC: rectal bleeding [RB], stool frequency [SF]; CD: abdominal pain [AP], liquid stools [LS]) and outcome duration. RESULTS: A total of 133 UC (76 VDZ; 57 anti-TNFα) and 174 CD (69 VDZ; 105 anti-TNFα) patients were included. By Week 26, estimated cumulative rates of patients achieving CR or symptom resolution with VDZ vs anti-TNFα treatment were for UC: CR, 53.7% vs 31.7%; RB, 66.8% vs 55.8%; and SF, 59.8% vs 50.7%, respectively; and for CD: CR, 14.4% vs 32.8%; AP, 62.5% vs 56.0%; and LS, 29.9% vs 50.3%, respectively. Outcomes were sustained similarly between treatments, except RB (VDZ vs anti-TNFα: median 38.1 vs 15.1 weeks, P = 0.03). Treatment-related adverse events occurred in 5.3% vs 7.0% (UC) and 8.7% vs 19.0% (CD) of VDZ vs anti-TNFα patients, respectively. CONCLUSIONS: Although there were differences in CR, symptom resolution, and safety profiles, real-world data support both VDZ and anti-TNFα as effective treatment options in UC and CD.

Dabrafenib plus trametinib is effective in the treatment of BRAF V600-mutated metastatic melanoma patients: analysis of patients from the dabrafenib plus trametinib Named Patient Program (DESCRIBE II).

In clinical trials, dabrafenib plus trametinib improved overall survival (OS) compared with single-agent BRAF inhibitors (BRAFi) in patients with BRAF V600-mutant unresectable or metastatic melanoma. We investigated dabrafenib plus trametinib therapy in a compassionate-use setting [Named Patient Program (NPP); DESCRIBE II]. A retrospective chart review of patients with BRAF V600-mutated unresectable stage III/IV melanoma receiving dabrafenib plus trametinib as compassionate use was conducted. Treatment patterns and duration, clinical outcomes, and tolerability were evaluated. Of 271 patients, 92.6% had stage IV melanoma, including 36.5% with brain metastases. Overall, 162 patients (59.8%) were BRAFi naive and 171 (63.1%) received first-line dabrafenib plus trametinib. Among BRAFi-naive patients, the overall response rate (ORR) was 67.3%, median OS (mOS) was 20.0 months, and median progression-free survival (mPFS) was 7.5 months. In BRAFi-naive patients with known brain metastases (n = 62), ORR was 61.3%, mOS was 15.5 months, and mPFS was 6.2 months. Eighty-four patients received BRAFi monotherapy for >30 days and switched to dabrafenib plus trametinib prior to progression. Of these 84 patients, 63 had known disease status at the time of switch, and 22 improved with the combination therapy. No new safety signals were identified, and dabrafenib plus trametinib was well tolerated. Dabrafenib plus trametinib showed substantial clinical activity in NPP patients with BRAF V600-mutated unresectable or metastatic melanoma. Analysis of treatment patterns demonstrated the effectiveness of the combination in patients with brain metastases and across lines of therapy with a well tolerated and manageable safety profile.

Early Access to Medicines Scheme: real-world data collection.

Real-world data (RWD) generated during the pre-approval phase could be supplementary to primary clinical trial outcomes; however, as we discuss here, a data collection framework is needed to ensure the validity and applicability of these data.

Extracting data from a chemotherapy prescription platform for real-world oncology research in the UK: a pilot study.

Aim: In the UK, there are limited data sources for evaluating real-world research questions related to oncology therapy. We conducted a pilot study to investigate the feasibility of extracting data directly from a chemotherapy prescription platform (ChemoCare®) utilized in standard care. Patients & methods: Concordance was compared with data extracted manually for patients with advanced melanoma as part of a concurrent chart review (gold-standard) using Cohen's kappa and the intraclass correlation coefficient. Results: There was high concordance between data automatically extracted from the prescription platform and chart review data. Conclusion: This pilot can be used as a framework for future studies using direct, automated extraction from prescription platforms.

Timing of GLP-1 Receptor Agonist Initiation for Treatment of Type 2 Diabetes in the UK.

INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) who fail to meet glycaemic control are at increased risk of diabetes complications. For patients who cannot maintain glycaemic control with oral medication, one recommended option is to add an injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) to their treatment regimen. The purpose of this study was to examine time to treatment intensification with GLP-1 RAs, including the duration of time that patients did not maintain glycaemic control with oral medication. METHODS: This was a medical record review conducted in the UK via a physician survey. Patients eligible to have their records reviewed were required to be ≥ 18 years of age, have a confirmed T2DM diagnosis, and have initiated GLP-1 RA treatment for T2DM in the past 6 months. All glycated haemoglobin (HbA1c) values within 5 years prior to GLP-1 RA initiation were collected. RESULTS: A total of 113 physicians contributed data for 1096 patients (mean age at the time of GLP-1 RA initiation was 54.9 years, 55.4% were male, and 71.4% were White). Median time from T2DM diagnosis to GLP-1 RA initiation was 6.1 years. Median consecutive time patients taking oral regimens were not under glycaemic control (HbA1c > 7.0%) prior to GLP-1 RA initiation was 13.5 months. Patients treated by general practitioners (GPs) had a significantly longer duration of time with insufficient glycaemic control prior to GLP-1 RA initiation compared with patients treated by diabetes specialists (median time for specialists was 11.0 months vs. 17.0 months for GPs; p = 0.038). CONCLUSIONS: Results suggest that treatment intensification is often delayed despite consistently poor glycaemic control for more than 12 months, contrary to treatment guideline recommendations. Findings from this study highlight that some T2DM patients may benefit from more rapid treatment intensification, which could improve glycaemic control and reduce the risk for many short- and long-term health complications.

Effectiveness of dabrafenib in the treatment of patients with BRAF V600-mutated metastatic melanoma in a Named Patient Program.

Given the approval of dabrafenib in patients with BRAF-mutant metastatic melanoma, a better understanding of treatment patterns and clinical outcomes with dabrafenib in a clinical setting is warranted. We performed a retrospective chart review of patients who received dabrafenib in a compassionate use setting through the Named Patient Program (DESCRIBE I study) during December 2010-August 2013 in Europe, New Zealand and Australia. Of the 331 Named Patient Program patients included, the majority (95.8%) had stage IV disease at dabrafenib initiation and 39.9% had brain metastases (BMs). Dabrafenib was used first line in 67.7% of patients, and median treatment duration was 6.4 months. Dabrafenib was well tolerated. Common grade 2/3 adverse events were hyperkeratosis (7.6%), pyrexia/fever (6.6%), fatigue (5.1%), hand-foot syndrome (5.4%) and nausea (3.6%). Overall response rate was 45.9%, median progression-free survival was 5.2 months (95% confidence interval, 4.2-6.1 months), and median overall survival was 12.4 months (95% confidence interval, 10.2-15.0 months). In patients with known brain metastases (n = 132) versus patients without (n = 199), overall response rate was 42.4% versus 48.2%, progression-free survival was 3.9 months (95% confidence interval, 3.8-5.5 months) versus 5.9 months (95% confidence interval, 4.8-7.8 months) and overall survival was 9.5 months (95% confidence interval, 6.7-12.4 months) versus 15 months (95% confidence interval, 11.1-20.5 months), respectively. Safety and effectiveness of dabrafenib in patients with unresectable advanced BRAF V600-mutant melanoma treated in an Named Patient Program was similar to the clinical trial experience, demonstrating effectiveness of dabrafenib in a nontrial setting.

Long-term safety and survival with gefitinib in select patients with advanced non-small cell lung cancer: Results from the US IRESSA Clinical Access Program (ICAP).

BACKGROUND: This is the first report of long-term (>10 years) safety, tolerability, and survival data on patients with non-small cell lung cancer (NSCLC) who received treatment with gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. METHODS: Patients with advanced NSCLC (N = 191) who entered the IRESSA Clinical Access Program (ICAP) (June 2011 to January 2013) and had previously obtained a clinical benefit from gefitinib therapy (including patients who had received gefitinib since 2001) were analyzed for adverse events (AEs). A subset of patients (n = 79) underwent retrospective chart review to capture demographic, safety, and survival data. RESULTS: Seventy-five of 191 patients (39%) remained on long-term gefitinib therapy as of September 2016. Overall, serious AEs (SAEs) were reported in 64 patients (34%), the majority of which were attributed to underlying disease or comorbidities; only 3 patients (1.6%) had SAEs that were considered as possibly gefitinib-related. In the retrospective chart review cohort, 70% of patients were women; 58% were former smokers, and 30% were never-smokers; 56% were diagnosed with adenocarcinoma, and 13% were diagnosed with squamous carcinoma. Although EGFR mutational status was tested in only 17 patients (22%), it was assumed that most tumors were EGFR-mutation-positive. The median duration of gefitinib therapy was 11.1 years (7.8 years before and 3.5 years during ICAP), with 10-year and 15-year survival rates of 86% and 59%, respectively, from the initiation of therapy. CONCLUSIONS: A subset of long-term NSCLC survivors who were receiving gefitinib had an excellent long-term safety profile. Although it is assumed that most of these patients' tumors harbor EGFR mutations, molecular studies of available tumor specimens are planned to uncover the features that predict long-term survival. Cancer 2018;124:2407-14. © 2018 American Cancer Society.

Real-world chart review study of adverse events management in patients taking tyrosine kinase inhibitors to treat metastatic renal cell carcinoma.

PURPOSE: The purpose is to describe management of adverse events of special interest across tyrosine kinase inhibitors approved for metastatic renal cell carcinoma. METHODS: We conducted a retrospective chart review in metastatic renal cell carcinoma patients initiating tyrosine kinase inhibitor monotherapy between 15 November 2010 and 15 November 2013, and experiencing ≥ 1 adverse events of special interest (diarrhea, fatigue, hand-foot syndrome, hypertension, or stomatitis/mucositis) within 3 months of initiation. Demographics, medical history, treatment regimens, and adverse events of special interest management data for 3.5 months postonset were collected. RESULTS: In 220 charts from 27 centers, tyrosine kinase inhibitors prescribed included sunitinib (55%), pazopanib (27%), axitinib (9%), and sorafenib (8%). During the study period, patients experienced 376 adverse events of special interest (13% serious). Fatigue was most common (62% of patients), followed by hypertension (37%), diarrhea (30%), stomatitis/mucositis (29%), and hand-foot syndrome (12%). Over half (56%) the adverse events of special interest were resolved or resolving. Treatment discontinuation due to adverse events of special interest occurred in 15% of patients. Prophylaxis was rarely provided (8%), whereas 59% of patients received adverse events of special interest treatment (pharmacologic (55%) and/or nonpharmacologic (7%)), 27% received tyrosine kinase inhibitor dose management, 23% received both adverse events of special interest treatment and dose management, and 31% received neither. Hypertension was the most treated (72% of all events), and fatigue was the least treated (9%); only 4% of patients received pharmacologic treatment for fatigue. CONCLUSIONS: Most adverse events of special interest were nonserious and more than half of the patients received pharmacologic and/or nonpharmacologic treatment. Fatigue was the most common yet least frequently treated adverse event of special interest, and few patients received prophylaxis or nonpharmacologic treatment. More emphasis on treatment and prophylaxis options for bothersome adverse events is warranted.

Treatment patterns and clinical outcomes with pazopanib in patients with advanced soft tissue sarcomas in a compassionate use setting: results of the SPIRE study.

BACKGROUND: A named patient program (NPP) was designed to provide patients with advanced soft-tissue sarcoma (aSTS) access to pazopanib, a multitargeted tyrosine kinase inhibitor. The SPIRE study was a retrospective chart review of participating patients. PATIENTS AND METHODS: Eligibility criteria for the NPP and SPIRE mirrored those of the pivotal phase-III study, PALETTE, which compared pazopanib with placebo in patients ≥18 years with aSTS and whose disease had progressed during or following prior chemotherapy or were otherwise unsuitable for chemotherapy. Outcomes of interest included treatment patterns, treatment duration, relative dose intensity, progression-free survival (PFS), overall survival (OS), clinical benefit rate, adverse events (AEs) and reasons for treatment discontinuation. RESULTS: A total of 211 patients were enrolled (median age 56 years; 60% female). Most patients received pazopanib in second- and third-line therapy (28.0% and 28.4%, respectively), followed by fourth line (19.0%) and ≥ fifth line (18.5%). The median duration of pazopanib treatment was 3.1 months (95% CI: 2.8-3.8), with a mean daily dose of 715 mg equating to 92% of recommended dose. Median OS was 11.1 months and clinical benefit rate was 46%. There was evidence of some clinical benefit across most histological subtypes. At study end, 40% of patients were alive and of these, 18% remained on pazopanib. Thirteen percent (13%) of patients discontinued pazopanib due to AEs. CONCLUSIONS: The SPIRE study demonstrated activity of pazopanib in heavily pretreated aSTS patients in a compassionate use setting. No new safety concerns were noted. Reassuringly, the relative dose intensity of pazopanib was 92%.

Assessing health-state utility values in patients with metastatic colorectal cancer: a utility study in the United Kingdom and the Netherlands.

PURPOSE: This study aimed to elicit EuroQol Quality of Life 5-Dimensions (EQ-5D) utility values from patients with second-line metastatic colorectal cancer (mCRC) pre- and post-progression. METHODS: A cross-sectional study was conducted in five hospitals in the Netherlands and the UK. Patients with mCRC were eligible if prescribed a second or subsequent line of therapy or best supportive care (BSC), received prior oxaliplatin in first-line therapy, and had Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-2 at second-line initiation. Patients completed the EuroQol Quality of Life 5-Dimensions 3-levels (EQ-5D-3L) questionnaire and were categorized as pre- or post-progression. Chart data including patient demographics, clinical history, prior/current treatments and serious adverse events (SAEs) were collected. Mean utilities were estimated; uni- and multivariate analyses were conducted. RESULTS: Seventy-five patients were enrolled; 42 were pre-progression defined as second line or third line following an AE on second line and 33 were post-progression defined as third or subsequent therapy lines or BSC. Patient/disease characteristics and number of SAEs were similar between cohorts. Mean utility scores were 0.741 (SD = 0.230) and 0.731 (SD = 0.292) for pre- and post-progression cohorts, respectively. Compared to pre-progression, more patients reported increased anxiety/depression (36 vs. 12 %) and fewer problems with daily activities (64 vs. 38 %) post-progression. More patients pre-progression were on active treatment at enrolment (83 vs. 42 %) compared to post-progression. CONCLUSIONS: This is the first real-world study to collect utilities for patients with second-line mCRC pre- and post-disease progression. Utility values were similar pre- and post-progression. To further explore the effect of radiological progression on utilities, longitudinal research is required that includes patients in palliative care centres.

Comparing patient and endoscopist perceptions of the colonoscopy indication.

BACKGROUND: determining whether a colonoscopy is performed for screening or nonscreening purposes can facilitate clinical practice and research. However, there is no simple method to determine the colonoscopy indication using patient medical files or health administrative databases. OBJECTIVE: to determine patient-endoscopist agreement on the colonoscopy indication. METHODS: a cross-sectional study was conducted among staff endoscopists and their patients at seven university-affiliated hospitals in Montreal, Quebec. The study participants were 50 to 75 years of age, they were able to understand English or French, and were about to undergo colonoscopy. Self- (endoscopist) and interviewer-administered (patient) questionnaires ascertained information that permitted classification of the colonoscopy indication. Patient colonoscopy indication was defined as the following: perceived screening (routine screening, family history, age); perceived nonscreening (follow-up); medical history that implied nonscreening; and a combination of the three preceding indications. Agreement between patient and endoscopist indications was measured using concordance and Kappa statistic. RESULTS: in total, 702 patients and 38 endoscopists participated. The three most common reasons for undergoing colonoscopy were routine screening/regular check-up (33.8%), follow-up to a previous problem (30.2%) and other problem (24.6%). Concordance (range 0.79 to 0.85) and Kappa (range 0.58 to 0.70) were highest for perceived nonscreening colonoscopy. Recent large bowel symptoms accounted for 120 occurrences of disagreement in which the patient perceived a nonscreening colonoscopy while the endoscopist perceived a screening colonoscopy. CONCLUSIONS: patient self-report may be an acceptable means for rapidly assessing whether a colonoscopy is performed for screening or nonscreening purposes. Delivery of patient-centred care may help patients and endoscopists reach a shared understanding of the reason for colonoscopy.