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Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancer diagnoses, and approximately 35% of patients with NSCLC are diagnosed at an early stage (I–IIIA). This study aimed to describe epidermal growth factor receptor (EGFR) testing, patient characteristics, and overall survival (OS) among patients with early-stage NSCLC in Denmark. Patients with early-stage NSCLC registered in the Danish Lung Cancer Registry in 2013–2018 were followed through 2019. We described EGFR testing, descriptively summarised patient characteristics, and calculated OS by EGFR testing and mutation status. The association between EGFR mutation (EGFRm) and all-cause mortality was estimated using Cox proportional-hazards regression, in subgroups defined by stage at diagnosis, age at diagnosis, comorbidity, and receipt of surgery. In 2013–2018, 21,282 patients with NSCLC were registered in the Danish Lung Cancer Registry, of whom 8758 were diagnosed at an early stage. Of those, 4071 (46%) were tested for EGFRm at diagnosis. Median OS was 5.7 years among patients with EGFRm-positive status (n = 361) and 4.4 years among patients with EGFRm-negative status (n = 3710). EGFRm-positive status was associated with lower all-cause mortality in all subgroups. This study contributes to population-based evidence on the epidemiology of early-stage NSCLC treated in routine clinical practice.

Purpose To investigate real-world clinical outcomes in patients with BRCA-mutated (BRCAm), HER2-negative metastatic breast cancer (mBC) according to BRCA and hormone receptor (HR) status. Methods Patients diagnosed with HER2-negative mBC between 01 January 2010 and 31 December 2018 were retrospectively identified from the American Society of Clinical Oncology’s CancerLinQ Discovery® database. Time to first subsequent therapy or death (TFST) from date of mBC diagnosis and start of first-line treatment for mBC and overall survival (OS) from date of mBC diagnosis were investigated according to BRCA status (BRCAm, BRCA wild type [BRCAwt] or unknown BRCA [BRCAu]) and HR status (positive/triple negative breast cancer [TNBC]). Follow-up continued until 31 August 2019 (i.e. minimum of 8 months). Results 3744 patients with HER2-negative mBC were identified (BRCAwt, n = 460; BRCAm, n = 83; BRCAu, n = 3201) (HR-positive, n = 2738). Median (Q1, Q3) age was 63.0 (54.0, 73.0) years. Median (95% confidence interval [CI]) TFST (months) from mBC diagnosis was as follows: HR-positive, 7.7 (5.0, 11.2), 8.3 (6.6, 10.2) and 9.4 (8.7, 10.1); TNBC, 5.4 (3.9, 12.4), 5.6 (4.7, 6.6) and 5.4 (5.0, 6.2) for BRCAm, BRCAwt and BRCAu, respectively. Median (95% CI) OS (months) was as follows: HR-positive, 41.1 (31.5, not calculable), 55.1 (43.5, 65.5) and 33.0 (31.3, 34.8); TNBC, 13.7 (11.1, not calculable), 14.4 (10.7, 17.0) and 11.7 (10.3, 12.8) for BRCAm, BRCAwt and BRCAu, respectively. Conclusion When stratified by HR status, TFST and OS were broadly similar for patients with HER2-negative mBC, irrespective of BRCA status. Further global real-world studies are needed to study outcomes of this patient population.

Background Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line (1L) therapy for EGFR mutation-positive (EGFRm) advanced/metastatic non-small cell lung cancer (NSCLC). Objective Our objective was to describe real-world treatment patterns and T790M testing practices in patients with 1L disease progression (Europe/USA) following treatment with first- or second-generation EGFR-TKIs. Methods This was a retrospective, non-interventional medical record review of patients with EGFRm locally advanced/metastatic NSCLC from routine clinical practice (EGFR-TKI initiation: 1 January 2015 to 31 December 2017; follow-up: last available medical record). Endpoints were demographic/clinical characteristics, incidence of central nervous system (CNS) metastases/leptomeningeal disease, second-line (2L) treatment, T790M mutation testing, and osimertinib treatment prevalence. Results Among 469 patients, 73% (n = 341/469) progressed on 1L EGFR-TKI treatment. Of those who progressed, 74% (n = 252/341) were tested for T790M, with 50% (n = 126/252) testing positive; 75% (n = 94/126) of T790M-positive patients received osimertinib (mostly 2L). Of the patients with progression, 24% (n = 83/341) did not receive 2L treatment, and 88% (n = 73/83) of these patients died. At diagnosis of advanced disease, 9% of patients (n = 41) had CNS metastases; at EGFR-TKI initiation, 14% of patients (n = 68) had CNS metastases. Over the study period, 11% of patients (n = 42) developed CNS metastases not detected at NSCLC diagnosis. Conclusions Rates of resistance mutation testing and subsequent utilization of recommended 2L therapies could be improved. As more targeted therapies are developed, it will be crucial to improve the molecular testing rates to ensure patients receive appropriate, effective, and timely treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s40801-021-00261-8.

Epidermal growth factor receptor (EGFR) mutations (EGFRm) are common oncogene drivers in non-small cell lung cancer (NSCLC). This real-world study explored treatment patterns and time to receive EGFRm test results in patients with advanced EGFRm NSCLC.A cross-sectional medical chart review was completed May-August 2020 in Australia, Canada, Germany, Italy, South Korea, Taiwan, UK, and USA. Eligible patients had advanced NSCLC and a positive EGFRm test result January-December 2017. Data were abstracted from NSCLC diagnosis to end of follow-up (31 March 2020) or patient's death whichever occurred earlier. The index date was the date of EGFRm confirmation.223 physicians provided data for 1,793 patients. Patients' mean age was 64.7 years, 54 % were male, 30.7 % had no history of smoking. Overall, 78 % of EGFRm test results were received ≤ 2 weeks after request (range of median 7-14 days across countries). Median time from advanced NSCLC diagnosis to EGFRm test result was 18 days (median range 10-22 days across countries). Over a third (37 %) of patients received a systemic treatment prior to EGFRm result; chemotherapy (25 %) and EGFR-TKI (15 %) were most commonly prescribed; post-EGFR test-result was EGFR-TKI (68 %); 80 % of patients initiated EGFR-TKI at any time point post-NSCLC diagnosis. Of those receiving a first-line EGFR-TKI post-EGFRm testing, 84 % received a TKI alone, 12 % in combination with chemotherapy, and 3 % with other treatments. Median time from first-line EGFR-TKI initiation post-EGFRm testing to first subsequent treatment was 19.8 months.Over one-fifth of patients wait14 days for their EGFRm test results, affecting their likelihood of receiving first-line EGFR-TKI with 20 % of patients never receiving EGFR TKI treatment. There was significant inter-country variability in the proportion of patients receiving EGFR TKIs. Our study highlights the need to improve EGFRm testing turnaround times and treatment initiation across countries.

Introduction: The preferred first-line (1L) treatment for epidermal growth factor receptor (EGFR) mutation-positive (EGFRm) advanced/metastatic non-small lung cancer (NSCLC) are EGFR-tyrosine kinase inhibitors (TKIs). However, most patients treated with 1L first- or second-generation (1G/2G) EGFR-TKIs acquire resistance; the EGFR T790M mutation is observed in ~30–50% of patients. We report real-world NSCLC treatment and T790M testing patterns in South Korea and Taiwan. Methods: Retrospective medical record review of EGFRm advanced/metastatic NSCLC patients from routine practice. 1G/2G EGFR-TKI initiation 1 January 2015–31 December 2017 (follow-up end date: last available medical record or August 2019). Study measures: demographic/disease characteristics, 1L/2L treatment, T790M testing. Results: In South Korea, 70% (164/235) and in Taiwan 89% (89/100) experienced 1L disease progression (median [range] follow-up: 22 [2.3–50.7] months). Of those with disease progression, 68% (111/164) and 62% (55/89) had T790M testing in South Korea and Taiwan, respectively. In South Korea, 43% (48/111) were T790M-positive with 88% (n=42/48) receiving osimertinib (mostly 2L). In Taiwan, 18% (10/55) were T790M-positive; 100% received osimertinib. Overall, 73% (120/164) and 63% (63/100) in South Korea and Taiwan, respectively, received 2L therapy, predominantly pemetrexed-containing regimens. Among patients with disease progression, 9% (14/164) and 24% (21/89) died before receiving 2L therapy in South Korea and Taiwan, respectively. Conclusion: In both countries

Background: Limited epidemiological data exist on the real-world outcomes in patients with BRCA-mutated (BRCAm), HER2− metastatic breast cancer (mBC). This study describes clinical outcomes in this population according to germline BRCA mutation (gBRCAm) and hormone receptor (HR) status. Methods: Patients diagnosed with HER2− mBC between January 1, 2010 and December 31, 2018 were retrospectively selected from the American Society of Clinical Oncology (ASCO)’s CancerLinQ Discovery® database. The primary objective was to describe, as a surrogate for progression-free survival, the time to first subsequent therapy or death (TFST; whichever came first), calculated from date of mBC diagnosis, according to gBRCAm status (gBRCAm, gBRCA wild-type [gBRCAwt] or unknown gBRCA [gBRCAu]) and HR status (+/−). TFST was also calculated from first-line systemic therapy initiation. The secondary objective was to describe overall survival (OS), calculated from date of mBC diagnosis. Kaplan-Meier medians and 95% confidence intervals (CIs) were estimated. Results: 3744 patients with HER2− mBC were identified (gBRCAwt, n=460; gBRCAm, n=83; gBRCAu, n=3201); 2738 patients were HR+. Median (Q1, Q3) age was 63.0 (54.0, 73.0) years. Median (95% CI) TFST (months), calculated from date of mBC diagnosis, was 9.2 (8.6, 9.9) in HR+ patients, 5.4 (5.1, 6.0) in HR− patients, and 7.1 (5.0, 9.2), 6.9 (6.1, 8.1) and 8.4 (7.9, 9.1) in gBRCAm, gBRCAwt and gBRCAu cohorts, respectively. Median (95% CI) OS (months) was 34.30 (32.70, 36.40) in HR+ patients, 12.0 (11.1, 13.3) in HR− patients, and 31.5 (23.1, 42.8), 34.7 (28.9, 44.5), 27.6 (26.1, 29.5) in gBRCAm, gBRCAwt and gBRCAu cohorts, respectively. Median TFST and OS stratified by both HR and BRCA mutation status are shown in Table 1. Conclusions: When stratified by HR status, median TFST and OS were broadly similar for patients with mBC, regardless of BRCA mutation status, as captured in the CancerLinQ Discovery® database. Outcomes may have been affected by class of first-line treatment received in a time preceding poly (ADP-ribose) polymerase inhibitor introduction as a targeted treatment for BRCAm patients. Further studies will be required to support these findings. Funding: This study was funded by AstraZeneca. Table 1. Median TFST and OSCohort TFST, n (events)a,bMedian TFST from mBC diagnosis, months (95% CI)Median TFST from first-line treatment initiation, months (95% CI)OS, n (events)aMedian OS, months(95% CI)gBRCAm, HR+(n=47)45 (40)7.7 (5.0, 11.2)6.6 (3.2, 9.0)47 (21)41.1 (31.5, NR)gBRCAm, HR−(n=29)20 (19)5.4 (3.9, 12.4)3.1 (2.2, 8.9)29 (18)13.7 (11.1, NR)gBRCAwt, HR+(n=296)277 (234)8.3 (6.6, 10.2)6.5 (5.7, 8.7)296 (128)55.1 (43.5, 65.5)gBRCAwt, HR−(n=130)113 (101)5.6 (4.7, 6.6)4.1 (3.4, 5.2)130 (91)14.4 (10.7, 17.0)gBRCAu, HR+(n=2395)2174 (1949)9.4 (8.7, 10.1)7.3 (6.9, 8.0)2395 (1431)33.0 (31.3, 34.8)gBRCAu, HR−(n=609)466 (425)5.4 (5.0, 6.2)4.2 (3.7, 4.6)609 (448)11.7 (10.3, 12.8)an refers to the number of patients at risk.bFor patients with no indication of a further line of therapy or death, TFST was censored at the last activity date.CI, confidence interval; gBRCAm, germline BRCA-mutated; gBRCAu, unknown germline BRCA mutation; gBRCAwt, germline BRCA wild-type; HR, hormone receptor; NR, not reached; OS, overall survival; TFST, time to first subsequent therapy or death. Citation Format: Robert S Miller, Stella Mokiou, Aliki Taylor, Miao Jiang, Ping Sun, Susan McCutcheon. Real-world clinical outcomes of patients with BRCA-mutated (BRCAm) HER2-negative metastatic breast cancer: A CancerLinQ® study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-66.

Most patients with epidermal growth factor receptor mutation-positive (EGFRm) non-small-cell lung cancer (NSCLC) acquire resistance to first-line (1L) first- or second-generation (1G/2G) EGFR-TKIs; therefore, it is important to optimize 1L treatment to improve patient outcomes. To retrospectively examine treatment patterns in locally advanced/metastatic NSCLC using MarketScan® Commercial and Medicare Supplemental Databases (all US census regions). Adults with a lung cancer diagnosis code between 1 January 2015–31 March 2018 were analyzed from diagnosis (index) through a variable-length follow-up. Patients had ≥ 1 pharmacy claim for 1G/2G EGFR-TKIs on or within 60 days post-index. Data were stratified by presence or absence of central nervous system (CNS) metastases (30 days pre-index through study end). 578 patients were included (median age 63 years, 64% female). Median follow-up was 13.5 months. The most frequently prescribed 1L EGFR-TKI was erlotinib (414/578, 72%). Median time to 1L treatment discontinuation was 8.2 (95% confidence interval (CI) 6.9, 9.0) months in patients diagnosed with CNS metastases at any time, and 7.7 (95% CI 6.9, 8.9) months in patients without CNS metastases. 270/578 patients (47%) discontinued 1L EGFR-TKIs; 209/270 (77%) initiated second-line (2L) therapy, most frequently osimertinib (96/209, 46%). In an analysis of US claims data, nearly half of patients discontinued 1L EGFR-TKIs, and 46% who initiated 2L received osimertinib. As nearly a quarter of patients who discontinued 1L EGFR-TKIs did not receive 2L treatment, this study highlights the need for optimal 1L treatment in EGFRm locally advanced/metastatic NSCLC.

Mutations in exons 18-21 of the epidermal growth factor receptor gene (EGFR) can confer sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small-cell lung cancer (NSCLC). Deletions in exon 19 or the exon 21 L858R substitution comprise approximately 85% of mutations, but comparatively few data are available on the remaining "uncommon" mutations. We conducted a systematic literature review to identify evidence on uncommon EGFR mutations in locally advanced/metastatic NSCLC (PROSPERO registration number: CRD42019126583). Electronic screening and congress searches identified studies published in 2012-2020 including patients with locally advanced/metastatic NSCLC and uncommon EGFR mutations (excluding T790M). We assessed the prevalence of uncommon mutations (in studies using direct sequencing of exons 18-21), and compared response to treatment and progression-free survival (PFS) in patients with common versus uncommon mutations and in those with exon 20 mutations versus other uncommon mutations. We identified 64 relevant studies. Uncommon mutations constituted 1.0-18.2% of all EGFR mutations, across 10 studies. The most frequently reported uncommon mutations were G719X (0.9-4.8% of all EGFR mutations), exon 20 insertions (Ex20ins; 0.8-4.2%), L861X (0.5-3.5%), and S768I (0.5-2.5%). Patients with common mutations typically experienced better treatment response and longer PFS on EGFR-TKIs than patients with uncommon mutations; Ex20ins mutations were associated with less favourable outcomes than other uncommon mutations. This review shows that uncommon mutations may comprise a clinically significant proportion of the EGFR mutations occurring in NSCLC, and highlights disparities in EGFR-TKI sensitivity between different uncommon mutations.

A systematic literature review was conducted to quantify populations of patients with primary breast cancer in whom bone metastases were detected at study start or during follow-up. Searches were performed in PubMed and EMBASE using terms related to breast cancer and bone metastases. Articles had to have been published 01/01/99–31/12/13, and to report data on the proportion of patients with bone metastases among patients with breast cancer. In total, 156 articles were included in the meta-analysis. A median of 12% of patients with stage I–III breast cancer developed bone metastases during a median follow-up of 60 months. Of patients who developed metastatic disease during follow-up, 55% (median) had bone metastases. Of those with metastatic breast cancer at study start, 58% (median) had bone metastases. These data help to inform on the global burden of bone metastases by defining patient populations that are at risk of developing bone metastases., SCOPUS: re.j, info:eu-repo/semantics/published

There is limited comparative evidence of the outcomes of different types of surgical management in patients with malignant melanoma in Europe. To address that gap we conducted a systematic literature review to summarize studies reporting outcomes of surgical procedures in patients with malignant melanoma in Europe. Medline was searched for European studies published in English, between 2004 and 2014 reporting surgical outcomes in adults with cutaneous malignant melanoma. We identified 23 studies that evaluated 18 332 patients treated surgically between 1979 and 2009 from 11 European countries. Most of the studies (21/23) were observational; the two remaining studies were randomized controlled trials (RCTs). Studies compared the effect of a range of surgical interventions on a range of clinical outcomes, more commonly overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS). Wider excisions were not associated with improved survival in patients with melanoma thickness ≥2 mm in both studies (RCTs), however, recent results based on long-term follow-up data associate 3 cm excision margins (vs. 1 cm) with favourable survival outcomes. There was some evidence that complete lymph node dissection after positive sentinel lymph node offers survival benefits over therapeutic lymph node dissection. Sentinel lymph node biopsy was not shown to be associated with significant OS benefits, however, it was overly related with higher rates of DFS/RFS. This review highlights the difficulties of making comparisons between different types of surgical procedures for malignant melanoma. As surgery remains the main treatment, this is an important field, and further evidence, particularly from RCTs, is needed.

Cutaneous malignant melanoma (CMM) incidence is increasing globally, making a thorough understanding of the disease and its outcomes essential for optimizing care. In this population-based, retrospective study, we investigated stage-specific survival and recurrence/progression rates of CMM among patients diagnosed in Stockholm County Council during 2005-2012, before the wide introduction of targeted therapy. A total of 3554 CMM patients from the Stockholm Melanoma Register were included. Information on comorbidities, progression, death, and treatments was obtained from nationwide registers and hospital electronic medical records. Unadjusted five-year survival varied from 91.4% for stage I to 24.6% for stage IV patients. Stage, age and gender were predictors of survival, with gender an independent predictor of survival for stages IA and IIA. 74.6% of patients remained recurrence/progression-free during follow-up, with five-year recurrence/progression-free survival rates varying from 85.3% to 12.9% among stage I and IV patients, respectively. In addition to stage, male gender, age, and circulatory system comorbidities increased the risk for recurrence/progression. No statistically significant differences in progression rate for operated and non-operated patients could be detected, possibly due to high rate (98.9%) of surgery. Our estimates of survival and recurrence rates are consistent with historical and global expectations and can serve as a baseline to gauge population-level improvements with use of novel melanoma treatments. This article is protected by copyright. All rights reserved.

7064 Background: Overall survival (OS) is the gold standard outcome in clinical cancer research but many clinical trials cannot assess long-term OS. Real-world data sources can be used to calculate long-term OS, but only if vital status is accurately captured. Methods: The primary goal was to assess concordance of death dates from CLQD and an external source, and the effect of incorporation of external death data on estimates of OS. CLQD obtains electronic medical record (EMR) data from participating US oncology sites. Under-reporting of vital status is a common problem with EMR data; we investigated the value of including death data from a commercially available database, obituarydata.com (OBD) into CLQD. OBD pulls death data from published obituaries across the US. A matching algorithm is used to match patients in CLQD and OBD. OBD death data from breast, lung, ovarian, and pancreatic cancer patients diagnosed between 2010–2018 supplemented the CLQD in this study. OS was calculated using Kaplan-Meier estimation; Pearson correlation was used for comparing time to death. Results: The addition of OBD modestly changes OS estimates (see Table). Among a subset of patients with death dates in both CQLD and OBD, dates were highly correlated for breast (r = 0.98), lung (r = 0.93), ovarian (r = 0.99), and pancreatic (r = 0.88) cancers. When date differences existed, they were ≤10 days for > 95% of the patients. These results suggest death dates are reliable in CLQD EMRs. OS curves were as expected, with OS decreasing by stage and age at diagnosis. Conclusions: Incorporating OBD modestly improves OS estimates and shows that when death data is present in CLQD, it is reliable. Future enhancements will focus on improving sensitivity of mortality ascertainment with external data linkages, without compromising specificity. [Table: see text]

Bone is the most common metastatic site associated with breast cancer. Using a database of women with breast cancer treated at Guy's Hospital, London 1976-2006 and followed until end 2010, we determined incidence of and survival after bone metastases.We calculated cumulative incidence of bone metastases considering death without prior bone metastases as a competing risk. Risk of bone metastases was modelled through Cox-regression. Survival after bone metastases diagnosis was calculated using Kaplan-Meier methodology.Of the 7064 women, 589 (22%) developed bone metastases during 8.4 years (mean). Incidence of bone metastases was significantly higher in younger women, tumour size5 cm, higher tumour grade, lobular carcinoma and ≥ four positive nodes, but was not affected by hormone receptor status. Median survival after bone metastases diagnosis was 2.3 years in women with bone-only metastases compared with1 year in women with visceral and bone metastases. There was a trend for decreased survival for patients who developed visceral metastases early, and proportionately fewer patients in this group.Incidence of bone metastases has decreased but bone metastases remain a highly relevant clinical problem due to the large number of patients being diagnosed with breast cancer.

Background Bone is a frequent site for metastases among women with breast cancer. We conducted a study using the General Practice Research Database (GPRD), with linkage to the National Cancer Registry (NCR) and Hospital Episode Statistics (HES), to estimate the incidence of bone metastases in women with breast cancer in the United Kingdom. Methods We identified all women in the GPRD aged 20–99 with a first-time diagnosis of breast cancer between 2000 and 2006. To address potential underreporting, we developed and validated an algorithm to serve as a proxy for bone metastases. Bone metastases were defined as (1) a bone cancer diagnosis code on the same day or following breast cancer diagnosis date, or (2) another metastasis code plus codes consistent with bone metastases diagnosis or treatment using the algorithm. We sent questionnaires to a sample of general practitioners to validate these definitions. Results We included 13,207 breast cancer patients (median age at diagnosis of 61 years) who contributed 70,885 person-years of follow-up. The majority of patients had stage 1 or 2 breast cancer (90.4%), and 2.6% had metastatic breast cancer at diagnosis. We identified 788 women (6.0%) with bone metastases after a median follow-up of 5.4 years. Questionnaire results validated the diagnosis of bone metastases in 88% of patients with a bone cancer code and for 70% identified with the algorithm. Conclusion This is the first time the GPRD has been linked to HES and NCR to study the epidemiology of bone metastases, adding important information on the burden of bone metastasis.

Objective Treatment options for patients with recurrent ovarian carcinoma are diverse, and different therapies are recommended based on platinum-free interval (PFI). Data examining the association between platinum sensitivity, treatment strategy, and outcomes are limited, particularly for partially platinum-sensitive (PPS) patients. This study characterized clinical features and outcomes in patients with recurrent ovarian carcinoma in the context of sensitivity to platinum-based therapy. Methods Anonymized case records were obtained from eligible European medical sites. Eligible patients were 18 years or older with epithelial ovarian carcinoma who had received 1 or more platinum-based therapies and had 1 or more subsequent relapses. Patient records were categorized by PFI and analyzed based on demographic and clinical data using descriptive statistics. Results There was no difference between PFI in PPS patients receiving platinum versus nonplatinum therapy (8.9 [range, 6.0–12.0] and 8.3 [range, 6.0–11.3] months, respectively). Overall survival in patients with platinum-sensitive, PPS, platinum-resistant, and platinum-refractory disease was 43.0 (95% confidence interval [95% CI], 25.1–42.3), 20.5 (95% CI, 17.7–24.8), 12.7 (95% CI, 10.4–14.2), and 9.8 (95% CI, 6.6–14.9) months, respectively. Among PPS patients, overall survival was 23.5 (95% CI, 18.4–37.3) and 18.7 (95% CI, 11.0–23.5) months for those who received platinum and nonplatinum-based therapy, respectively. No demographic or clinical characteristics were identified that indicated a difference between PPS patients who received platinum-based therapy versus those who did not. Conclusions Partially platinum-sensitive patients with recurrent ovarian carcinoma who received platinum-based therapy had improved outcomes compared with those who did not. No clear demographic criteria for choosing platinum- versus nonplatinum-based therapy for PPS patients were identified from patient records.

Contains fulltext : 152566.PDF (Publisher’s version ) (Open Access) BACKGROUND: From 2008-2013, the European indication for panitumumab required that patients' tumor KRAS exon 2 mutation status was known prior to starting treatment. To evaluate physician awareness of panitumumab prescribing information and how physicians prescribe panitumumab in patients with metastatic colorectal cancer (mCRC), two European multi-country, cross-sectional, observational studies were initiated in 2012: a physician survey and a medical records review. The first two out of three planned rounds for each study are reported. METHODS: The primary objective in the physician survey was to estimate the prevalence of KRAS testing, and in the medical records review, it was to evaluate the effect of test results on patterns of panitumumab use. The medical records review study also included a pathologists' survey. RESULTS: In the physician survey, nearly all oncologists (299/301) were aware of the correct panitumumab indication and the need to test patients' tumor KRAS status before treatment with panitumumab. Nearly all oncologists (283/301) had in the past 6 months of clinical practice administered panitumumab correctly to mCRC patients with wild-type KRAS status. In the medical records review, 97.5% of participating oncologists (77/79) conducted a KRAS test for all of their patients prior to prescribing panitumumab. Four patients (1.3%) did not have tumor KRAS mutation status tested prior to starting panitumumab treatment. Approximately one-quarter of patients (85/306) were treated with panitumumab and concurrent oxaliplatin-containing chemotherapy; of these, 83/85 had confirmed wild-type KRAS status prior to starting panitumumab treatment. All 56 referred laboratories that participated used a Conformite Europeenne-marked or otherwise validated KRAS detection method, and nearly all (55/56) participated in a quality assurance scheme. CONCLUSIONS: There was a high level of knowledge amongst oncologists around panitumumab prescribing information and the need to test and confirm patients' tumors as being wild-type KRAS prior to treatment with panitumumab, with or without concurrent oxaliplatin-containing therapy.

Contains fulltext : 153716.pdf (Publisher’s version ) (Closed access) BACKGROUND: The use of epidermal growth factor receptor inhibitors to treat metastatic colorectal cancer (mCRC) patients requires prior confirmation of tumour wild type (WT) RAS mutation status (exons 2/3/4 for KRAS or NRAS). This retrospective pooled analysis aims to robustly estimate RAS mutation prevalence and individual variation patterns in mCRC patients. METHOD: Individual patient data from five randomised, controlled panitumumab studies (three phase III, one phase II and one phase Ib/II) were pooled for this analysis. The phase III studies included mCRC patients independent of RAS mutation status; the phase II and Ib/II studies included mCRC patients with confirmed WT KRAS exon 2 status. Four studies conducted RAS testing using Sanger sequencing; one study used a combination of next-generation sequencing and Sanger sequencing. In order to assign overall RAS status, the mutation status of all exons 2/3/4 KRAS or NRAS was required to be known. RESULTS: Data from 3196 mCRC patients from 36 countries were included in the analysis. The overall unadjusted RAS mutation prevalence in mCRC patients was 55.9% (95% confidence interval (CI): [53.9-57.9%]), with the following distribution observed: KRAS exon 2 (prevalence 42.6% [40.7-44.5%]); KRAS exon 3 (3.8% [2.9-4.9%]); KRAS exon 4 (6.2% [5.0-7.6%]); NRAS exon 2 (2.9% [2.1-3.9%]); NRAS exon 3 (4.2% [3.2-5.4%]); NRAS exon 4 (0.3% [0.1-0.7%]). Differences in RAS mutation prevalence estimates were observed by study (p=0.001), gender (p=0.030), and by country (p=0.028). CONCLUSIONS: This analysis provides robust estimates of overall RAS mutation prevalence and individual variation patterns in mCRC patients.

To assess and characterize the temporal variation in ovarian cancer incidence and mortality by age within countries in the Americas, Europe, Asia, and Oceania.Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program in the United States (U.S.) were used to assess ovarian cancer incidence rates (1998-2008) and mortality rates, (1988-2007 for 12-month survival, 1988-2006 for 24-month survival, and 1988-2003 for 60-month survival), stratified by age at diagnosis. Data from GLOBOCAN were used to calculate country-specific incidence rates for 2010 and 2020 and case-fatality rates for 2010.A statistically significant decrease in Annual Percent Change (APC) of ovarian cancer incidence was observed in the U.S. for all women (-1.03%), among women who were diagnosed at65 years of age (-1.09%) and among women who were diagnosed at ≥65 years of age (-0.95%). There was a statistically significant increase in the observed APC for survival at 12-months (0.19%), 24-months (0.58%), and 60-months (0.72%) for all women; however, 5-year survival for advanced stage (III or IV) disease was low at less than 50% for women65 years and less than 30% for women ≥65 years. Global results showed a wide range in ovarian cancer incidence rates, with China exhibiting the lowest rates and the Russian Federation and the United Kingdom exhibiting the highest rates.Ovarian cancer survival has shown modest improvement from a statistical perspective in the U.S. However, it is difficult to ascertain how clinically relevant these improvements are at the population or patient level.

Background Given the increasing incidence in cutaneous malignant melanoma (CMM) and the recent changes in the treatment landscape, it is important to understand stage-specific overall and recurrence-free survival patterns in Europe. Despite publications such as EUROCARE-5, there is limited information on stage-specific survival for CMM in Europe. Method We carried out a systematic literature review to provide an up-to-date summary of stage-specific survival and recurrence-free survival patterns in patients with CMM in Europe. Studies were included if they were published in Medline during the past 12 years and included information on stage-specific survival and/or recurrence in CMM. Results Of the 8,749 studies identified, 26 studies were included, representing nine countries. Collectively, the studies covered a population of 152,422 patients and included data from 1978 to 2011. Randomized clinical trials and single-center observational studies comprised the most common study designs, including five large registry-based studies. Stage-specific information for survival and recurrence varied: 5-year overall survival: 95%–100% (stage I), 65%–92.8% (stage II), 41%–71% (stage III), and 9%–28% (stage IV); 5-year relapse-free survival was reported less frequently: 56% (stage II), and 28%–44% (stage III). Studies reporting survival by sentinel node (SN) status reported 5-year overall survival as 80%–95% for negative SN (stage I/II) and 35%–75% for positive SN (stage III) status; recurrence-free survival at 5 years: 76%–90% for negative and 35%–58% for positive SN status. Some studies included comparisons of survival by key patient sociodemographic characteristics, suggesting that these have a substantial influence on survival and recurrence estimates. Conclusion The studies identified in this review show large variations in stage-specific overall and recurrence-free survival by study type and by country. Owing to differing study designs and populations, it is difficult to make detailed comparisons. Large population-based studies that include stage-specific survival and recurrence in Europe are therefore important.

Background Hepatic metastases develop in approximately 50% of colorectal cancer (CRC) cases. We performed a review and meta-analysis to evaluate survival after resection of CRC liver metastases (CLMs) and estimated the summary effect for seven prognostic factors. Methods Studies published between 1999 and 2010, indexed on Medline, that reported survival after resection of CLMs, were reviewed. Meta-relative risks for survival by prognostic factor were calculated, stratified by study size and annual clinic volume. Cumulative meta-analysis results by annual clinic volume were plotted. Results Five- and 10-year survival ranged from 16% to 74% (median 38%) and 9% to 69% (median 26%), respectively, based on 60 studies. The overall summary median survival time was 3.6 (range: 1.7–7.3) years. Meta-relative risks (95% confidence intervals) by prognostic factor were: node positive primary, 1.6 (1.5–1.7); carcinoembryonic antigen level, 1.9 (1.1–3.2); extrahepatic disease, 1.9 (1.5–2.4); poor tumor grade, 1.9 (1.3–2.7); positive margin, 2.0 (1.7–2.5); >1 liver metastases, 1.6 (1.4–1.8); and >3 cm tumor diameter, 1.5 (1.3–1.8). Cumulative meta-analyses by annual clinic volume suggested improved survival with increasing volume. Conclusion The overall median survival following CLM liver resection was 3.6 years. All seven investigated prognostic factors showed a modest but significant predictive relationship with survival, and certain prognostic factors may prove useful in determining optimal therapeutic options. Due to the increasing complexity of surgical interventions for CLM and the inclusion of patients with higher disease burdens, future studies should consider the potential for selection and referral bias on survival.

Aim: Few observational studies have reported adverse events and comorbidities in European ovarian cancer patients. We conducted a retrospective study to address these areas. Methods: A retrospective cohort study of advanced (stage IIIB-IV) or recurrent ovarian cancer (OC) patients treated by hospital or cancer centre-based physicians (n = 23) was conducted in France. 127 patients diagnosed with OC between 2009 and 2012 and with a minimum follow-up of 6 months were included. Retrospective information on comorbidities, treatment-related adverse events (AEs) (captured over a maximum 1 year period), and deaths was abstracted into case report forms. Results: Of the 127 patients, 92 (72.4%) had advanced OC and 35 (27.6%) had recurrent OC; the median age was 62 years. 86.6% of patients had surgery performed during the most recent admission. 35 (27.6%) patients recurred after initial presentation, of which 16 were highly platinum sensitive (recurrence more than 12 months after stopping platinum based therapy), 11 were platinum partially-sensitive (recurrence 6-12 months of stopping platinum based therapy), 7 were platinum resistant (recurrence within 6 months of stopping platinum-based therapy or progression while receiving 2nd or later line platinum based therapy), and 1 was platinum refractory (recurrence within 6 months of the start date of 1st-line platinum-based therapy). A total of 73 comorbidities were reported in 44 patients (34.6% of patients). Vascular (10.2%), metabolism (7.1%), respiratory (5.5%), and psychiatric disorders (5.5%) were the most common. Incidence of AEs was 77.2%, of which 12.6% were classified as serious. The most common AEs were anaemia (16.5%), hematologic events (12.6%), taste change (11.8%), and headache (7.1%). Throughout the follow-up period, 12 patient deaths were reported (6 due to disease progression). Conclusions: In a European hospital-based study of advanced or recurrent ovarian cancer patients, one in three patients were reported to have a comorbidity, and four in five reported a mild adverse event. The incidence rates reported in this study are comparable to those reported in previous European-based studies. Disclosure: A. Taylor, V. Chia and G. Kafatos: is employed by Amgen Ltd and owns Amgen stock; D. Pillas: is employed by Amgen Ltd; G. Freyer: is a consultant for Amgen France. All other authors have declared no conflicts of interest.

Objectives To measure crude and cumulative incidence of BM and cumulative survival after diagnosis of BM. BM were grouped by (i) BM only (ii) BM followed by visceral metastases (iii) visceral metastases followed by BM. Methods Kaplan-Meier and Cox regression database analysis of women with breast cancer diagnosed 1975-2006 and treated at Guys Hospital London, whose details were prospectively updated regularly till end 2010. Results Of 7064 women, 1589 (22%) developed BM by end follow-up (mean 8.4 years); 2254 (32%) were diagnosed with breast cancer Conclusion Incidence of BM has decreased in recent years and risk of BM is significantly affected by clinical tumour characteristics. Women with bone only metastases survive longer with their disease. BM remain an important target for prevention, treatment and palliation in breast cancer. Disclosure A. Taylor: I own shares with Amgen and work at Amgen. All other authors have declared no conflicts of interest.

Jonathan Montomoli,1 Stephen Jacques Hamilton-Dutoit,2 Trine Frøslev,1 Aliki Taylor,3 Rune Erichsen11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark; 3Centre for Observational Research, Amgen, Uxbridge, UKBackground: The occurrence of KRAS mutations and their association with prognosis in metastatic colorectal cancer patients is not well documented in population-based studies.Objectives: To examine the feasibility of identifying archived colorectal cancer specimens, and through linkage with nationwide Danish population-based databases to investigate the prevalence of KRAS mutations and their association with colorectal cancer survival.Methods: We used the Danish Pathology Database to identify the physical location of primary (or in some cases secondary) tumor specimens from selected metastatic colorectal cancer patients referred to our hospital for palliative chemotherapy between November 1, 2008 and September 30, 2009. Routinely stored paraffin tissue blocks were obtained from the pathology archives of the originating hospital. KRAS mutation tumor status was assessed for each patient using the commercialized TheraScreen KRAS Mutation Kit. Using the unique identifier number, we linked the patients to the Danish National Registry of Patients and the Danish Civil Registration System to obtain data on date of first colorectal cancer diagnosis and follow-up status. We estimated prevalence of KRAS mutations and the 1-, 2-, and 5-year survival after colorectal cancer diagnosis using the Kaplan–Meier technique.Results: We identified 106 metastatic colorectal cancer patients (64% males). All were successfully linked to the registries, and archived tumor-tissue samples were obtained and analyzed in each case. The overall prevalence of KRAS mutations was 55%, and 1-, 2-, and 5-year overall survival after colorectal cancer diagnosis was 91%, 68%, and 25%, respectively.Conclusion: It is feasible to use Danish population-based registries to obtain archived tissue samples from metastatic colorectal cancer patients, and to estimate prevalence of KRAS mutation and subsequently evaluate the association with colorectal cancer survival.Keywords: feasibility study, KRAS, colorectal neoplasms, survival, registries

e13599 Background: Simultaneous inhibition of both the PI3K-Akt and RAF/MEK/ERK pathways may yield greater benefits than inhibiting either pathway alone. This phase I study (NCT01021748) examined the safety, pharmacokinetics (PK), pharmacodynamics (PD), maximal tolerated dose (MTD), and preliminary antitumor activity of the combination of a MEKi (selumetinib) and AKTi (MK-2206). Methods: Eligible patients (pts) with advanced solid tumors were treated with MK-2206 either every other day (QOD) or once weekly (QW), in combination with selumetinib administered either once daily (QD) or twice daily (BID). Results: 51 pts with advanced solid tumors (15 colon, 8 NSCLC, 6 ovarian, 5 pancreatic, 3 breast and 14 others) were treated across 9 dose levels. There were 2 confirmed partial response (PR) (1 NSCLC, ongoing > 52 wks; 1 ovarian, on treatment for 47 weeks; both KRAS mutation positive), 1 unconfirmed PR (pancreatic, on treatment 20 wks), and 24 pts with stable disease (ranged from 6 to 47 wks). Preliminary assessment of PK data suggested no apparent drug-drug interactions with unaltered PK profiles of each drug when administered in combination. Conclusions: In combination the maximum tolerated doses of MK-2206 and selumetinib are 135 mg QW and 100 mg QD, respectively. This combination of investigational agents demonstrated preliminary antitumor activity in pts with advanced cancer. [Table: see text]

Background Most cases of colorectal cancer (CRC) arise from adenomatous polyps and malignant potential is greatest in high risk adenomas. There is convincing observational evidence that red and processed meat increase the risk of CRC and that higher levels of physical activity reduce the risk. However, no definitive randomised trial has demonstrated the benefit of behaviour change on reducing polyp recurrence and no consistent advice is currently offered to minimise patient risk. This qualitative study aimed to assess patients’ preferences for dietary and physical activity interventions and ensure their appropriate and acceptable delivery to inform a feasibility trial. Methods Patients aged 60–74 included in the National Health Service Bowel Cancer Screening Programme (NHSBCSP) were selected from a patient tracking database. After a positive faecal occult blood test (FOBt), all had been diagnosed with an intermediate or high risk adenoma (I/HRA) at colonoscopy between April 2008 and April 2010. Interested patients and their partners were invited to attend a focus group or interview in July 2010. A topic guide, informed by the objectives of the study, was used. A thematic analysis was conducted in which transcripts were examined to ensure that all occurrences of each theme had been accounted for and compared. Results Two main themes emerged from the focus groups: a) experiences of having polyps and b) changing behaviour. Participants had not associated polyp removal with colorectal cancer and most did not remember being given any information or advice relating to this at the time. Heterogeneity of existing diet and physical activity levels was noted. There was a lack of readiness to change behaviour in many people in the target population. Conclusions This study has confirmed and amplified recently published factors involved in developing interventions to change dietary and physical activity behaviour in this population. The need to tailor the intervention to individuals, the lack of knowledge about the aetiology of colon cancer and the lack of motivation to change behaviour are critical factors. Trial registration Current Controlled Trials ISRCTN03320951