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  • American Society of Clinical Oncology (ASCO)  (85)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 1 ( 2021-01-01), p. 66-78
    Abstract: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 18_suppl ( 2012-06-20), p. LBA4000-LBA4000
    Abstract: LBA4000 Background: EGFR overexpression occurs in 27-50% of esophagogastric adenocarcinomas (OGA), and correlates with poor prognosis. The REAL3 trial evaluated the addition of the anti-EGFR antibody panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in advanced OGA. Methods: Patients with untreated, metastatic or locally advanced OGA were randomised to EOC (E 50mg/m2, O 130mg/m2, C 1250mg/m2/day) or mEOC+P (E 50mg/m2, O 100mg/m2, C 1000mg/m2/day, P 9mg/kg). Primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), response rate (RR), toxicity, and biomarker evaluation. Response was evaluated by RECIST after 4 and 8 cycles. Following IDMC review in October 2011 trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. Results: 553 patients were recruited (EOC 275, mEOC+P 278), with median follow-up 5.0 and 5.2 months respectively. Median OS was 11.3 months with EOC compared to 8.8 months with mEOC+P (HR 1.37: 95% CI 1.07-1.76, p=0.013). Median PFS was 7.4 and 6.0 months respectively (HR 1.22: 95% CI 0.98-1.52, p=0.068), with RR being 42% compared to 46% (odds ratio 1.16: 95% CI 0.81-1.57, p=0.467). mEOC+P was associated with ↑ G3/4 diarrhoea (17% vs 11%), skin rash (14% vs 1%) and thrombotic events (12% vs 7%), but ↓ haem toxicity ( 〉 G3 neutropenia 14% vs 31%). In the mEOC+P arm, OS was significantly improved in patients with G1-3 rash (77%, n=209) on treatment compared to those without (23%, n=63); median OS 10.2 vs 4.3 months (p 〈 0.001), with similar significant improvements seen in RR and PFS. Biomarker analysis in the first 200 patients has not identified other predictive markers associated with P therapy. Multivariate analysis for OS in these patients demonstrated a negatively prognostic role for KRAS mutation (HR 2.1: 95% CI 1.10-4.05, p=0.025) and PIK3CA mutation (HR 3.2: 95% CI 1.01-10.40, p=0.048). Conclusions: Addition of P to EOC chemotherapy was associated with worsening of OS in an unselected advanced OGA population. This may be in part due to lowered doses of O and C in the mEOC+P regimen. Outcomes in patients treated with P varied by grade of skin toxicity.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. LBA4000-LBA4000
    Abstract: LBA4000 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 91-91
    Abstract: 91 Background: The REAL3 trial evaluated the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in advanced OGA. We previously reported that addition of panitumumab was not associated with improvement in survival endpoints. In this analysis we aimed to explore factors associated with OS in the REAL3 population. Methods: Analysis performed in ITT population (n=553). OS was evaluated in relation to the baseline characteristics displayed in the table below. Cox regression was used to obtain HRs and 95% CIs. Factors with p 〈 0.2 were included in a forward stepwise model and factors with p 〈 0.1 were regarded as significant in the final model. OS was also assessed using the RMH Prognostic Index score which comprises 4 adverse variables: PS 2; liver mets; peritoneal mets; ALP 〉 100 U/L. Results: Results of the univariate analysis are shown in the table below. In multi-variate analysis, the factors which remained statistically significant for OS were: PS (p=0.080): 1 vs 0 HR 1.24 (95% CI 0.99-1.57); 2 vs 0 HR 1.57 (95%CI 0.97-2.54) Disease extent (p=0.054): Met disease vs LA HR 1.42 (95% CI 0.99-2.02) Baseline global health score (p=0.005): Low vs high HR 1.52 (95% CI 1.16-2.00); middle vs high HR 1.45 (95% CI 1.11-1.89) Patients with an RMH Prognostic Index score of 0 (good prognosis) had median OS of 13.1 mo. This compared to 9.5 mo in patients with 1-2 adverse features (intermediate prognosis) (HR 1.37, 95% CI 1.12-1.68; p=0.002) and 4.7 mo in patients with 3-4 adverse features (poor prognosis) (HR 4.02, 95% CI 1.96-8.22; p 〈 0.001). Conclusions: Baseline global quality of life may represent a useful adjunct to clinical parameters to guide prognostication in advanced OGA. These findings also validate the RMH Prognostic Index score in the REAL3 population. Clinical trial information: 2007-005976-15.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 18 ( 2023-06-20), p. 3339-3351
    Abstract: Efficacy and safety of niraparib + AAP for first-line treatment in patients with HRR+ mCRPC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 6_suppl ( 2018-02-20), p. 164-164
    Abstract: 164 Background: Germline mutations in DNA repair genes have been associated with poor prostate cancer outcomes in retrospectives studies. Such defects have been identified in 12% of mCRPC patients. Several studies are ongoing to assess the benefit of these patients from platinum-based chemotherapy and PARP inhibitors, but no conclusive data are available with regards to currently approved therapies for mCRPC, as Abiraterone or Enzalutamide. Methods: PROREPAIR-B (NCT03075735) is a prospective multicentre observational cohort study. Patients diagnosed with mCRPC, with unknown mutational status at study entry and who were going to start a first-line treatment for mCRPC were eligible. For this sub-analysis patients who received Abiraterone or Enzalutamide as first androgen receptor targeted therapy (ART) were selected. The endpoints of this sub-analysis included to assess the impact of BRCA1, BRCA2, ATM, PALB2 and other germline mutations in DNA repair genes on cause-specific survival (CSS), progression-free survival (PFS), time to PSA progression (bPFS) and response to the first ART received as 1 st or 2 nd line therapy. Results: 337 patients were eligible for this analysis. CSS from mCRPC was not significantly different between gDDR carriers and non-carriers. However, CSS from mCRPC in BRCA2 carriers was significantly shorter than in non-carriers (23.3 Vs 34.6 months, p = 0.02). CSS from first ART, PFS and response-rates were not significantly different between both groups. However, the bPFS was significantly shorter in patients harbouring gDDR mutations (7.3 Vs 3.8 months, p = 0.04), especially in BRCA2 carriers (7.3 Vs 3.0 months, p = 0.03). Conclusions: This is the first study to prospectively follow-up DNA repair germline mutations to determine the outcome on standard treatment for mCRPC. The results suggest that different gDDR defects may have different impact on mCRPC outcomes. Clinical trial information: NCT03075735.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21555-e21555
    Abstract: e21555 Background: Lung-ONE study aims to determine the clinical utility in making decisions on planned 2 nd line therapy in advanced NSCLC based on a comprehensive genomic profile (CGP) test as FoundationOne CDx or FoundationOne Liquid and describe alterations found on these patients. Methods: Lung-ONE included advanced/metastatic NSCLC patients being treated on first-line, with molecular diagnostic wild-type (or unknown) for at least ALK, EGFR, and ROS-1 genes. Patients treated with targeted therapies or immunotherapy were excluded. This interim analysis describes the findings of CGP from patients of Lung-ONE with driver genomic alterations (GAs) and the investigators decision to change the planned second line treatment or not. Patients continue being followed-up for up to 2 years. Results: As of November 15 2019, 152 patients were included. At the time of sampling, 90.7% had received ≥2 different chemotherapy regimens and other therapies. Main testing for ALK and ROS-1 was IHC in 91.4% and 73.8%, respectively; and for EGFR, it was qPCR in 99.3%. Planned 2nd-line based on routine molecular profile was chemotherapy and, mainly checkpoint inhibitors (61.7%). CGP was assayed on 102 (67.1%) tissue specimens and 50 (32.9%) blood samples. Of the 1,581 GAs identified in 141 patients, 541(34.2%) were potential drivers in 131. The most frequently mutated genes were TP53 in 72(55%) patients and KRAS in 52(40%). TMB and MSI signatures were calculated on 82 patients. 21% had 〈 = 16 mut/Mb. Other GAs of interest are presented in table. Therapeutic orientations were recommended for 116/152(76.8%) patients. In 39/151(25.8%) patients the GAs had approved drugs in NSCLC or other tumor types. CGP outcomes, would be used by 27% of oncologists to guide targeted 2nd-line. Conclusions: CGP detected mutations that are informative for choosing personalized treatment in 25%. CGP demonstrates the ability of detect druggable genomic alterations missed at diagnosis opening new treatment options. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 7 ( 2021-03-01), p. 723-733
    Abstract: Immunotherapy has revolutionized the treatment of advanced non–small-cell lung cancer (NSCLC). In two phase III trials (CheckMate 017 and CheckMate 057), nivolumab showed an improvement in overall survival (OS) and favorable safety versus docetaxel in patients with previously treated, advanced squamous and nonsquamous NSCLC, respectively. We report 5-year pooled efficacy and safety from these trials. METHODS Patients (N = 854; CheckMate 017/057 pooled) with advanced NSCLC, ECOG PS ≤ 1, and progression during or after first-line platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg once every 2 weeks) or docetaxel (75 mg/m 2 once every 3 weeks) until progression or unacceptable toxicity. The primary end point for both trials was OS; secondary end points included progression-free survival (PFS) and safety. Exploratory landmark analyses were investigated. RESULTS After the minimum follow-up of 64.2 and 64.5 months for CheckMate 017 and 057, respectively, 50 nivolumab-treated patients and nine docetaxel-treated patients were alive. Five-year pooled OS rates were 13.4% versus 2.6%, respectively; 5-year PFS rates were 8.0% versus 0%, respectively. Nivolumab-treated patients without disease progression at 2 and 3 years had an 82.0% and 93.0% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression-free at 5 years, respectively. Treatment-related adverse events (TRAEs) were reported in 8 of 31 (25.8%) nivolumab-treated patients between 3–5 years of follow-up, seven of whom experienced new events; one (3.2%) TRAE was grade 3, and there were no grade 4 TRAEs. CONCLUSION At 5 years, nivolumab continued to demonstrate a survival benefit versus docetaxel, exhibiting a five-fold increase in OS rate, with no new safety signals. These data represent the first report of 5-year outcomes from randomized phase III trials of a programmed death-1 inhibitor in previously treated, advanced NSCLC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 3_suppl ( 2015-01-20), p. TPS227-TPS227
    Abstract: TPS227 Background: The molecular characteristics of a pt’s tumour can determine their suitability for treatment with targeted drugs. Several molecular alterations are only seen in a small percentage of pts and so it is often necessary to screen many pts to identify those who may benefit from targeted therapies. Testing each pt for multiple biomarkers is also increasingly important. Targeted next generation sequencing (NGS) can rapidly interrogate tumours for actionable genetic aberrations and therefore facilitate a personalised treatment approach. FOrMAT aims to assess the feasibility of delivering validated NGS results (to accredited standards) in a clinically meaningful timeframe and how this could be adopted into routine clinical practice in the United Kingdom’s National Health Service. Methods: FOrMAT (ClinicalTrials.gov identifier NCT02112357) is a single-centre translational study in pts with locally advanced/metastatic GI tumours (including gastroesophageal, pancreatic, biliary tract and colorectal). Targeted capture sequencing is performed on archival or fresh biopsy samples to detect mutations, copy number variations and translocations in 45 genes which have prognostic, predictive or pharmacogenomic significance or are targets in current/upcoming clinical trials. Results are discussed by a Sequencing Tumour Board to establish if a pt is potentially suitable for a targeted therapy (e.g. within another clinical trial, as part of standard of care or via a compassionate access program). Changes to pts’ treatment are not mandated. The primary endpoint is the percentage of pts in whom a currently actionable molecular alteration was detected. Secondary endpoints include evaluation of the time required to obtain sequencing results. Blood samples will be collected at baseline and at the time of each tumour response assessment for analysis of molecular markers, including ctDNA and microRNA. Pts may also consent to optional biopsies for exploratory research into tumour heterogeneity and development of pt-derived organoids. The study aims to recruit 200 pts over 2 years. Recruitment started in February 2014 and to date 56 pts have been recruited. Clinical trial information: NCT02112357.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. 644-644
    Abstract: 644 Background: BRAF MT metastatic CRC (mCRC) is associated with a poor prognosis. For the first time, we report outcomes for BRAF MT mCRC at a single tertiary centre, compared to a matched control group, since introduction of routine somatic BRAF and RAS mutation testing. Methods: Pts with BRAF MT mCRC (diagnosed Oct 2010-Nov 2014) were compared to a matched group of BRAF wildtype (WT) pts treated in same time period who were randomly selected after matching for age, sex and stage. Demographic, tumour characteristic and treatment data were collected. Overall (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method and comparisons made using χ² test or Cox regression. Results: Of 503 pts tested, 59 (11.7%) had BRAF MT tumours (16 early stage, 16 recurrent and 27 de novo metastatic). Median age (years) at diagnosis was 68 (27-85) compared with 70 (29-85) for BRAF WT pts (p = 0.995). Median OS for pts with mCRC was 18.2 months (m) for BRAF MT and 41.1m for BRAF WT pts (HR 2.73 P 〈 0.01). For BRAF MT and BRAF WT pts with mCRC, median PFS on first-line treatment (1L) was 8.1m (n = 37) and 9.2m (n = 81) respectively (HR = 1.10 [P = 0.69]), PFS on 2L was 5.1m (n = 21) and 9.0m (n = 49) respectively (HR = 1.84 [P = 0.03] ) while PFS on 3L was 1.7m (n = 10) and 6.6m (n = 20) respectively (HR = 2.75 [P = 0.02]). Fluoropyrimidine based doublet regimens were used in 94.6%, 85.7% and 20% of BRAF MT pts in 1L, 2L and 3L respectively compared with 87.2%, 92.5% and 52.4% in BRAF WT pts. Pts with localised disease had a recurrence rate of 50% (16/32) for pts with BRAF MT compared with 52.4% (33/63) for BRAF WT pts (p = 0.83). Conclusions: In this case-control study, poor OS of pts with BRAF MT mCRC is associated with reduced clinical benefit beyond 1L. Sequential doublet chemotherapy remains a reasonable option in these pts. The role of BRAF mutation in predicting recurrence of early CRC warrants further study. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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