Severity: Warning
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Filename: drivers/Session_files_driver.php
Line Number: 177
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File: /var/www/html/index.php
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Function: require_once
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Filename: Session/Session.php
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File: /var/www/html/index.php
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Function: require_once
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
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Function: require_once
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Filename: models/Detail_model.php
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File: /var/www/html/application/models/Detail_model.php
Line: 71
Function: strpos
File: /var/www/html/application/controllers/Detail.php
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Function: insertAPISummary
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Function: require_once
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Message: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated
Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace
File: /var/www/html/application/controllers/Detail.php
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Function: formatAIDetailSummary
File: /var/www/html/index.php
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Function: require_once
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Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 257
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File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 258
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
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Function: file_get_contents
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Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
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Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
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Function: pubMedSearch_Global
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Function: pubMedGetRelatedKeyword
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File: /var/www/html/application/helpers/my_audit_helper.php
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Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: pubMedGetRelatedKeyword
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Function: require_once
Introduction: Osimertinib is an oral, central nervous system-active, EGFR tyrosine kinase inhibitor (TKI) for the treatment of EGFR T790M-positive advanced NSCLC. Here we have evaluated EGFR mutation frequencies in two phase II studies of osimertinib (AURA extension and AURA2).
Methods: After progression while receiving their latest line of therapy, patients with EGFR mutation-positive advanced NSCLC provided tumor samples for mandatory central T790M testing for the study selection criteria. Tumor tissue mutation analysis for patient selection was performed with the Roche cobas EGFR Mutation Test (European Conformity-in vitro diagnostic, labeled investigational use only) (Roche Molecular Systems, Pleasanton, CA). Patients should not have been prescreened for T790M mutation status. The cobas test results were compared with those of the MiSeq next-generation sequencing system (Illumina, San Diego, CA), which was used as a reference method.
Results: Samples from 324 and 373 patients screened for AURA extension and AURA2, respectively, produced valid cobas test results. The T790M detection rates were similar between AURA extension and AURA2 (64% and 63%, respectively). The pooled T790M rate was 63%, with no difference by ethnicity (63% for Asian and non-Asian patients alike) or immediately prior treatment with an EGFR TKI (afatinib, 69%; erlotinib, 69%; and gefitinib, 63%). A higher proportion of patients had T790M detected against a background of exon 19 deletions versus L858R mutation (73% versus 58% [p = 0.0002]). In both trials the cobas test demonstrated high sensitivity (positive percent agreement) and specificity (negative percent agreement) for T790M detection when compared with the next-generation sequencing reference method: positive percent agreement of 91% versus 89% and negative percent agreement of 97% versus 98%.
Conclusions: In both trials, the rate of detection of T790M mutation in patients with advanced NSCLC was approximately 63% and was unaffected by immediately prior treatment with an EGFR TKI or ethnicity.
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Source |
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http://dx.doi.org/10.1016/j.jtho.2017.05.002 | DOI Listing |
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