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The pertuzumab study in the neoadjuvant setting for HER2+ nonmetastatic breast cancer in Australia (PeRSIA-ML39622) is an analysis of safety and effectiveness data from the pertuzumab patient registry. Although the prognosis of patients with early stage HER2+ breast cancer has been greatly improved by advances in chemotherapy approximately 25% to 30% of patients develop recurrent disease. Our study aimed to examine the effectiveness of neoadjuvant pertuzumab on surgical outcomes, describe the medium-term effectiveness outcomes of patients treated with pertuzumab, and describe the planned and actual anticancer treatment regimens that patients received. Deidentified data were collected from the patients' medical records and entered into REDCap, between March 2018 and July 2019 (n = 95). The adverse events (AEs) reported most frequently were diarrhea (20; 21.1%), rash (4; 4.2%), and LVSD (4; 4.2%; two patients during neoadjuvant treatment and two patients during adjuvant treatment). AEs, ≥Grade 3 were diarrhea (2; 2.1%) and LVSD (1; 1.1%). Following surgery, a breast pathological complete response (bpCR) was achieved in 65 patients (70.7%; 95% CI: 60.2%-79.7%) and total pathological complete response (tpCR) in 59 patients (64.1%; 95% CI: 53.4%-73.9%). All patients who did not achieve a tpCR obtained a partial response (33/92, 35.9%). Our study is the first to capture real-world data on the use of pertuzumab in the neoadjuvant setting in Australia. The effectiveness and safety data are consistent with those reported in clinical trials of pertuzumab in patients with HER2+ breast cancer, with no new safety concerns.
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Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Pérsia , Austrália , Diarreia/induzido quimicamenteRESUMO
PURPOSE: Dual anti-HER2 targeted therapy and chemotherapy is the current first-line standard of care for HER2 + metastatic breast cancer (MBC), with endocrine therapy (ET) the backbone of treatment in hormone receptor positive (HR +) disease. The potential ET benefit in HER2 + /HR + patients is unknown as pivotal dual anti-HER2 clinical trials precluded ET use. METHODS: Real-world data from a multi-site registry of consecutive HER2 + MBC patients treated at clinician discretion were examined. Patients that were HR + (ER + and/or PR +) and had received first-line chemotherapy alongside trastuzumab and pertuzumab were explored. Of 362 patients in the registry, 215 were excluded due to being HR- (n = 210) or not receiving chemotherapy (n = 5). RESULTS: Of the 147 patients included, 91 (62%) received concurrent ET and 56 (38%) had not. Comparing the groups, there were no significant differences in age, performance status, metastatic sites, use of previous therapy and de novo metastatic disease. More patients with ER + PR + disease versus those with ER + PR- or ER-PR + received ET (73 vs 45%). The addition of ET was associated with significantly improved 5-year PFS (HR 0.58, CI 0.37-0.89, p = 0.014) and OS (HR 0.52, CI 0.31-0.90, p = 0.018), with no increase in adverse events noted. CONCLUSION: The addition of ET to first-line dual anti-HER2 therapy post chemotherapy in patients with HER2 + /HR + MBC was associated with major gains in PFS and OS with no safety concerns evident. Further studies of this combination are justified, along with studies of how best to integrate other agents that are active in this patient subset, including CDK4/6 inhibitors.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptor ErbB-2 , Trastuzumab , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND: International practice guidelines recommend administration of bone-modifying agents (BMA) in metastatic breast cancer (MBC) patients with bone metastases to reduce skeletal-related events (SRE). Optimal delivery of BMA in routine clinical practice, including agent selection and prescribing intervals, remains unclear. AIM: To describe real-world practice of Australian breast oncologists. METHODS: Prospective data from February 2015 to July 2020 on BMA delivery to MBC patients with bone metastases was analysed from Treatment of Advanced Breast Cancer in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Australian Patient (TABITHA), a multi-site Australian HER2+ MBC registry. RESULTS: Of 333 HER2+ MBC patients, 171 (51%) had bone metastases at diagnosis, with a mean age of 58.1 years (range, 32-87). One hundred and thirty (76%) patients received a BMA, with 90 (69%) receiving denosumab and 40 (31%) receiving a bisphosphonate. Patients who received a BMA were more likely to have received concurrent first-line systemic anti-HER2 therapy (95% vs 83%; P = 0.04), to present with bone-only metastases at diagnosis (24% vs 7%; P = 0.02) and less likely to have visceral metastases (51% vs 71%; P = 0.03). Ten of 40 (25%) bisphosphonate patients and 45 of 90 (50%) denosumab patients received their BMA at the recommended 4-weekly interval. Prescribing intervals varied over time. Adverse events reported were consistent with clinical trial data. CONCLUSION: Three-quarters of Australian HER2+ MBC patients with bone metastases receive a BMA, often at different schedules than guidelines recommend. Further studies, including all MBC subtypes, are warranted to better understand clinicians' prescribing rationale and potential consequences of current prescribing practice on SRE incidence.
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Neoplasias Ósseas , Neoplasias da Mama , Humanos , Pessoa de Meia-Idade , Feminino , Neoplasias da Mama/patologia , Denosumab/uso terapêutico , Estudos Prospectivos , Austrália/epidemiologia , Receptor ErbB-2/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Difosfonatos , Sistema de RegistrosRESUMO
Clinical trials have strict eligibility criteria, potentially limiting external validity. However, while often discussed this has seldom been explored, particularly across cancer types and at variable time frames posttrial completion. We examined comprehensive registry data (January 2014 to June 2019) for standard first-line treatments for metastatic colorectal cancer (CRC), advanced pancreatic cancer (PC), metastatic HER2-amplified breast cancer (BC) and castrate-resistant prostate cancer (CaP). Registry patient characteristics and outcomes were compared to the practice-changing trial. Registry patients were older than the matched trial cohort by a median of 2-6 years (all P = <.01) for the CRC, BC and PC cohorts. The proportion of Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 patients was lower for CRC (94.1% vs 99.2%, P = .001) and BC (94.9% vs 99.3%, P = .001). Progression-free survival (PFS) for registry patients was similar to the trial patients or significantly longer (CaP, Hazard Ratio [HR] = 0.65, P = <.001). Overall survival (OS) was also similar or significantly longer (CaP, HR 0.49, P = <.001). In conclusion, despite real-world patients sometimes being older or having inferior PS to trial cohorts, the survival outcomes achieved were consistently equal or superior to those reported for the same treatment in the trial. We suggest that this is potentially due to optimised use of each treatment over time, improved multidisciplinary care and increased postprogression options. We can reassure clinicians and patients that outcomes matching or exceeding those reported in trials are possible. The potential for survival gains over time should routinely be factored into future trial statistical plans.
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Neoplasias da Mama/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Sistema de Registros , Estudos Retrospectivos , Padrão de Cuidado , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Multiple meta-analyses have demonstrated that routine surveillance following colorectal cancer surgery improves survival outcomes. There is limited data on how recurrence patterns and post-recurrence outcomes vary by individual tumor stage. METHODS: Using a multi-site community cohort study, we examined the potential impact of primary tumor stage on the sites of recurrence, management of recurrent disease with curative intent, and post-resection survival. We also explored changes over time. RESULTS: Of 4257 new colon cancers diagnosed 2001 through 2016, 789 (21.1%) had stage I, 1584 (42.4%) had stage II, and 1360 (36.4%) had stage III colon cancer. For consecutive 5-year periods (2001-2005, 2006-2010, 2011-2016), recurrence rates have declined (23.4 vs. 17.1 vs. 13.6%, p < 0.001), however, the resection rates of metastatic disease (29.3 vs. 38.6 vs. 35.0%, p = 0.21) and post-resection 5-year survival (52.0 vs. 51.8 vs. 64.2%, p = 0.12) have remained steady. Primary tumor stage impacted recurrence rate (3.8 vs. 12 vs. 28%, p < 0.0001 for stage 1, 2, and 3), patterns of recurrence, resection of metastatic disease, (50 vs. 42 vs. 30%, p < 0.0001) and post-resection 5-year survival (92 vs. 64 vs. 44%, p < 0.001). CONCLUSION: In this community cohort we defined significant differences in recurrence patterns and post-resection survival by tumor stage, with a diminishing rate of recurrence over time. While recurrence rates were lower with stage I and II disease, the high rate of metastatic disease resection and excellent post-resection outcomes help to justify routine surveillance in these patients.
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Neoplasias do Colo , Neoplasias Colorretais , Estudos de Coortes , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/patologia , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: Trastuzumab, pertuzumab, and docetaxel are the standard first-line therapy for HER2-positive (HER2+) metastatic breast cancer (MBC). However, only 10% of patients received neoadjuvant and/or adjuvant trastuzumab (NAT) in the registration trial (NCT00567190). In contemporary practice, the majority of recurrent HER2+ MBC patients had prior NAT. We explore any impact of prior therapy on the efficacy of dual HER2-targeted antibody with taxane therapy for metastatic disease. METHODS: Utilising a prospective national registry, clinico-pathological, treatment, and outcome data for HER2+ MBC patients diagnosed between October 2006 and January 2019 were collected. Survival was estimated by the Kaplan-Meier method and compared among groups by log-rank test. RESULTS: Of 287 HER2+ MBC patients, 222 (77%) received first-line trastuzumab, pertuzumab, and taxane therapy. There were 130 (45%) with de novo MBC. Of the recurrent MBC patients 107/157 (68%) had received NAT. The median progression-free survival (PFS) among patients who received NAT was 15.8 months compared with 24.3 months without prior NAT (hazard ratio [HR] 1.45, 95% CI 1.05-2.03, p = 0.03). The median overall survival (OS) was 42.7 months in patients who had NAT, and was not reached in those who did not (HR 1.80, 95% CI 1.12-2.90, p = 0.02). However, when excluding de novo MBC patients, prior NAT exposure was no longer significantly associated with survival (p = 0.11). De novo MBC patients had the longest median PFS (25.2 months) and OS (91.2 months). CONCLUSIONS: Prior receipt of NAT was associated with inferior median PFS following first-line HER2-based therapy in the metastatic setting. However, prior NAT exposure did not significantly impact OS, supporting the efficacy of taxane, trastuzumab, pertuzumab combination for first-line HER2+ MBC regardless of prior NAT exposure. Patients with de novo MBC had the longest survival, suggesting stratification for synchronous versus metachronous disease in prospective clinical trials of MBC should be considered.
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Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Prospectivos , Receptor ErbB-2/genética , Trastuzumab/uso terapêutico , Resultado do TratamentoRESUMO
While mismatch repair (MMR) deficiency has been studied extensively, the assessment of MMR status in colorectal and other cancers remains highly relevant, particularly in light of recent data demonstrating that MMR deficiency is a strong predictor for treatment benefit with immune checkpoint inhibitors across multiple tumor types. In colorectal cancer, there is a growing consensus in support of routine MMR testing for Lynch syndrome screening, to inform prognosis and adjuvant chemotherapy use in early stage disease, and to predict response to immunotherapy in advanced disease. Here, we provide a review of the Ventana MMR Immunohistochemistry Panel, which was recently approved by the US FDA for use in Lynch syndrome screening.
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Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Reparo de Erro de Pareamento de DNA/genética , Testes Genéticos/métodos , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Neoplasias Colorretais Hereditárias sem Polipose/terapia , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica/métodos , Programas de Rastreamento/métodos , Estadiamento de Neoplasias , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND: Congenital heart disease is common yet poorly understood in childhood. We reviewed the understanding of older children and adolescents with the commonest congenital heart defect, namely, a small ventricular septal defect (VSD), through a questionnaire and/or their drawings of their abnormality. METHODS: As part of a wider study, older children and adolescents with a small VSD were asked to draw a picture of their cardiac defect in addition to completing a questionnaire. RESULTS: Twelve of an initial cohort of 20 participants, who were between the ages of 8 and 20 years, completed a drawing of their malformation. Further drawings were obtained from five additional participants recruited from a private practice over the next few years. There were almost equal number of male and female participants overall. Nearly all participants had a limited understanding of their cardiac abnormality as reflected by their drawings. Nevertheless none reported restricting their physical activity. CONCLUSION: While most older children and adolescents did not seem to have a clear understanding of their small VSD, it did not appear to affect their daily activity. The participants placed a greater reliance on the information provided by their parents rather than their doctor, emphasizing the importance of informing both the parents and the patient.
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Comunicação Interventricular/psicologia , Educação de Pacientes como Assunto/métodos , Relações Médico-Paciente , Adolescente , Criança , Ecocardiografia , Feminino , Seguimentos , Comunicação Interventricular/diagnóstico , Humanos , Masculino , Inquéritos e Questionários , Adulto JovemRESUMO
Traditional cancer registries have often been siloed efforts, established by single groups with limited objectives. There is the potential for registry data to support a broad range of research, audit and education initiatives. Here, we describe the establishment of a series of comprehensive cancer registries across the spectrum of common solid cancers. The experience and learnings of each registry team as they develop, implement and then use collected data for a range of purposes, that informs the conduct and output of other registries in a virtuous cycle. Each registry is multi-site, multi-disciplinary and aims to collect data of maximal interest and value to a broad range of enquiry, which would be accessible to any researcher with a high-quality proposal. Lessons learnt include the need for careful and continuous curation of data fields, with regular database updates, and the need for a continued focus on data quality. The registry data as a standalone resource has supported numerous projects, but linkage with external datasets with patients in common has enhanced the audit and research potential. Multiple projects have linked registry data with matched tissue specimens to support prognostic and predictive biomarker studies, both validation and discovery. Registry-based biomarker trials have been successfully supported, generating novel and practice-changing data. Registry-based clinical trials, particularly randomised studies exploring the optimal use of available therapy options are now complementing the research conducted in traditional clinical trials. More recent projects supported by the registries include health economic studies, personalised patient education material, and increased consumer engagement, including consumer entered data.
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BACKGROUND: International guidelines recommend combining a CDK4/6 inhibitor and endocrine therapy (ET) as first line treatment for hormone receptor (HR) positive, HER2 negative metastatic breast cancer (MBC). Results from MONALEESA-2 demonstrate superior progression free survival (PFS) and overall survival (OS) with ribociclib (CDK4/6 inhibitor) and ET compared to ET alone. Real world outcomes have yet to be reported. MATERIALS AND METHODS: KARMA is a non-interventional registry of Australian patients receiving first-line treatment with ribociclib and aromatase inhibitor (AI), obtained via a Medicine Access Program (MAP) for HR+, HER2- MBC. Outcomes were compared with the ribociclib/letrozole cohort in MONALEESA-2. RESULTS: Data from 160 patients at 17 sites was analysed. Median follow-up is 36.5 months. Compared to MONALEESA-2, patients were numerically younger (54.3 vs. 62 years), with higher rates of bone-only metastases (31% vs. 21%). A total of 63 of 160 (39%) patients remain on treatment. A total of 56% of patients had at least 1 dose reduction, with neutropenia (68%) and abnormal liver enzymes (17%) the most common reasons. A total of 17 of 160 (11%) discontinued treatment due to toxicity, with no treatment related deaths. Median PFS was not reached (95% CI 29.9- NR), with PFS at 12 months and 18 months being 76% and 67% respectively versus 25.3 months, 73% and 63% in MONALEESA-2. CONCLUSION: The ribociclib and AI combination was well tolerated in this real-world setting. The KARMA registry cohort achieved a superior PFS (>36.5 months) to MONALEESA-2, potentially due to more favourable baseline disease characteristics. Less frequent assessment scheduling in this non trial setting may also contribute.
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Inibidores da Aromatase , Neoplasias da Mama , Humanos , Feminino , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/patologia , Letrozol , Receptores de Estrogênio , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Austrália , Receptor ErbB-2RESUMO
BACKGROUND: The development of brain metastases occurs commonly in HER2-positive metastatic breast cancer and is associated with a poorer prognosis. The advent of HER2-targeted therapy has improved overall survival, but the benefit in patients with brain metastases is unclear, as these patients are often excluded from clinical trials. This study aimed to explore real-world outcomes in patients with brain metastases in HER2-positive MBC. MATERIALS & METHODS: Data was extracted from the TABITHA registry, which consists of patient data collected prospectively from 16 Australian sites from 24th February 2015 to 31st October 2021. Data analysed included characteristics of brain metastases, treatment received and survival outcomes. RESULTS: A total of 135 (37%) of 361 patients with HER2-positive MBC were diagnosed with brain metastases during their clinical course, including 45 (12%) with brain metastases at time of MBC diagnosis. 61 (45%) had ≥4 brain lesions. The most common local therapy given was whole brain radiation therapy (WBRT) (36%) followed by multi-modality treatment with both surgery and radiation therapy (27%). The majority of patients received first-line HER2-targeted treatment with trastuzumab and pertuzumab followed by second-line trastuzumab emtansine (T-DM1) but third-line therapy was heterogenous. The median overall survival in patients who developed brain metastases was significantly shorter than those who did not develop brain metastases (58.9 vs. 96.1 months, P = .02). CONCLUSION: Real-world patients diagnosed with brain metastases in HER2-positive MBC have a relatively poor prognosis, despite advances in HER2-targeted treatment. As the range of HER2-targeted treatment expands, it is important to pursue clinical trials that focus on patients with brain metastases.
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Neoplasias Encefálicas , Neoplasias da Mama , Maitansina , Ado-Trastuzumab Emtansina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Austrália/epidemiologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Maitansina/efeitos adversos , Receptor ErbB-2/análise , Sistema de Registros , TrastuzumabRESUMO
BACKGROUND: The FIRE-3 [5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment colorectal cancer (CRC)] study reported that first-line FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab resulted in similar progression-free survival (PFS) but improved overall survival (OS). A potential explanation is that the initial biologic agent administered in metastatic CRC (mCRC) affects later line efficacy of the other treatments. We sought to test this hypothesis. MATERIALS AND METHODS: We interrogated our mCRC registry (Treatment of Recurrent and Advanced Colorectal Cancer) regarding treatment and outcome data for RAS wild-type patients receiving epidermal growth factor receptor inhibitors (EGFRIs) in second and subsequent lines. Survival outcomes from the beginning of EGFRI use were determined as a function of previous bevacizumab use and the interval between ceasing bevacizumab and beginning EGFRI use. RESULTS: Of 2061 patients, 222 eligible patients were identified, of whom 170 (77%) had received previous bevacizumab and 52 (23%) had not. PFS and OS from the start of EGFRIs did not differ by previous bevacizumab use (3.8 vs. 4.2 months; hazard ratio [HR], 1.12; P = .81; 9.0 vs. 9.2 months; HR, 1.19; P = .48, respectively) for the whole cohort or when analyzed by the primary tumor side (HR for left side, 1.07; P = .57; HR for right side, 1.2; P = .52). PFS was significantly shorter with right-sided primary tumors when the interval between bevacizumab and EGFRI use was < 6 versus > 6 months (median, 2.2 vs. 6 months; HR, 2.23; P = .01) but not with left-sided tumors (median, 4.2 vs. 5.5 months; HR, 1.12; P = .26). CONCLUSION: Previous bevacizumab use had no effect on the activity of subsequent EGFRIs. The apparent effect of time between biologic agents in right-sided tumors might reflect patient selection.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Sistema de Registros/estatística & dados numéricos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bevacizumab/farmacologia , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Cetuximab/farmacologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Conjuntos de Dados como Assunto , Receptores ErbB/antagonistas & inibidores , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Masculino , Intervalo Livre de ProgressãoRESUMO
PURPOSE: To evaluate the use of docetaxel in very elderly men with metastatic castration-resistant prostate cancer (mCRPC) treated in routine clinical care. METHODS: A retrospective case series of men with mCRPC aged ≥80 years and treated with docetaxel between July 2006 and June 2012 at three community hospitals in Melbourne, Australia. RESULTS: Twenty patients were identified, with a median age of 83 years (range 80-93 years). Aside from one patient treated weekly, all patients were treated with a 3-weekly regimen of docetaxel with a median of six cycles (range 1-10 cycles) delivered. Eight patients (40%) had an initial dose reduction and 11 patients (55%) had subsequent dose delays or reductions. Eight patients (40%) completed planned treatment. Grade 3/4 hematologic toxicity was observed in nine patients (45%), and five patients (25%) were admitted to hospital with chemotherapy-related complications. Prostate-specific antigen (PSA) response was assessable for 16 patients, of whom nine (56%) had a PSA response of ≥50% and one (6%) had a PSA-complete response. The median overall survival in this cohort was 13.4 months. CONCLUSIONS: Very elderly patients (80 + years) with mCRPC are infrequently included in clinical trials, yet the use of chemotherapy in this population is likely to increase. Our series demonstrates significant response rates to docetaxel chemotherapy, but that a substantial number of patients had treatment-related complications. This highlights the need for careful patient selection and optimization of chemotherapy dosing.
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AIM: As multiple new agents have been added to the treatment options for patients with metastatic colorectal cancer, survival outcomes in clinical trials have continued to improve. Similarly, improved outcomes in routine clinical care would be anticipated, but have yet to be demonstrated. Here, we aim to explore whether survival gains demonstrated in clinical trials are reproducible in routine practice, and whether factors beyond new therapies may be contributing to improved outcomes. METHODS: Comparison of comprehensive treatment and outcome data for consecutive patients diagnosed in 2003-2006 versus 2007-2010 at four specialist hospitals in Australia. RESULTS: Data were available on 965 patients; median age 66.1 years (range 19-93), 572 (59%) were male. For the latter time period, there was an increase in patients receiving any treatment (74% vs 66%, P = 0.014), initial combination chemotherapy (57% vs 44%, P < 0.001) and bevacizumab (15% vs 2%, P < 0.001). There was no change in the percentage undergoing resection of distant metastatic disease. For the latter time period, overall survival was improved (median 24.8 vs 17.4 months, P < 0.001), including patients not receiving any active treatment (11.9 vs 6.4 months, P = 0.014). CONCLUSION: Survival outcomes in routine clinical care for patients with metastatic colorectal cancer have markedly improved in recent years following the introduction of multiple new active therapies. The improved outcome of untreated patients suggests earlier diagnosis and improved supportive care may also be contributing to survival gains.