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Brian B Lentrichia
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OA 05 - Next Generation TKI (ID 657)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:James Chih-Hsin Yang, Fiona Blackhall
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 301 + 302
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OA 05.02 - Osimertinib vs SoC EGFR-TKI as First-Line Treatment in Patients with EGFRm Advanced NSCLC (FLAURA): Plasma ctDNA Analysis (ID 8978)
15:55 - 16:05 | Author(s): Brian B Lentrichia
- Abstract
- Presentation
Background:
FLAURA (NCT02296125) is a Phase III, double-blind, randomized study assessing efficacy and safety of osimertinib vs standard of care (SoC) EGFR-TKI as first-line treatment for patients with EGFRm advanced NSCLC. Concordance between tissue and plasma testing for EGFRm (Ex19del/L858R), and progression-free survival (PFS) by baseline plasma EGFRm status were evaluated.
Method:
Eligible patients: ≥18 years (Japan ≥20 years); Ex19del/L858R mutation-positive lung adenocarcinoma; no prior systemic anti-cancer/EGFR-TKI therapy for advanced NSCLC. Randomization: 1:1 to osimertinib 80 mg once daily (qd) orally (po) or SoC (gefitinib 250 mg or erlotinib 150 mg, qd po). At baseline, patients provided tumor tissue samples for central analysis of EGFRm status (cobas EGFR Mutation Test) and blood samples for retrospective analysis of EGFRm status by plasma ctDNA (cobas EGFR Mutation Test v2). PFS by baseline plasma EGFRm status was assessed. Comparison of EGFRm status between baseline tumor tissue and evaluable ctDNA samples was an exploratory endpoint.
Result:
Globally, 556 patients were randomized: osimertinib, n=279; SoC, n=277. Good concordance was observed between central laboratory tissue and plasma testing for EGFRm in the screened population (see table). In plasma EGFRm-positive patients (n=359), osimertinib (n=183) reduced the risk of progression or death by 56% vs SoC (n=176), hazard ratio (HR) 0.44 (95% CI 0.34, 0.57). This was consistent with the overall PFS result observed with osimertinib vs SoC in the full analysis set (FAS; tumor tissue EGFRm-positive by local/central testing), HR 0.46 (95% CI 0.37, 0.57); p<0.0001 and in plasma EGFRm-negative patients (n=124: osimertinib, n=60; SoC, n=64), HR 0.48 (95% CI 0.28, 0.80).Figure 1
Conclusion:
In the subgroup of plasma EGFRm-positive patients, clinical benefit of osimertinib was superior to SoC, consistent with the overall FLAURA FAS. These results, and good concordance between tissue and plasma testing for EGFRm, support the utility of plasma EGFRm testing for selecting patients eligible for first-line osimertinib treatment.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-068 - Investigation of Low Plasma/Tissue EGFR Concordance in Russia: Follow-up to the IGNITE Global Diagnostic Study (ID 10446)
09:30 - 09:30 | Presenting Author(s): Brian B Lentrichia
- Abstract
Background:
IGNITE was a large multi-national, non-comparative, non-interventional diagnostic study whose objective was to in part determine the concordance in EGFR mutation status between tissue/cytology and plasma testing in the real world setting[1]. Locally advanced or metastatic NSCLC patients were enrolled from 9 countries in Asia-Pacific including Russia. A very significant difference was observed in performance of plasma testing in Russia (PPV=39.3%) vs. Asia Pac (PPV=92.5%) vs tissue results with only 51/84 ctDNA EGFR mutation positive results from Russian labs confirmed by the corresponding tissue result. No single lab appeared to contribute predominantly to the questionable overall performance. 1. Han, B et al.; ‘Determining the prevalence of EGFR mutations in Asian and Russian patients (pts) with advanced non-small-cell lung cancer (aNSCLC) of adenocarcinoma (ADC) and non-ADC histology: IGNITE study’ (ELCC 2015 Abstract No. 96O).
Method:
142 of the 941 evaluable plasma samples from Russia were selected to include originally discordant samples and a similar number of concordant positive and concordant negative samples. All samples were shipped to an experienced lab and re-tested for TKI sensitizing mutations using the QIAamp Circulating Nucleic Acid Kit and the Therascreen® EGFR Plasma RGQ PCR test (Qiagen). The central laboratory was blinded to the origin of the samples and original EGFR mutation result.
Result:
Adhering to package insert defined criteria for the internal control, 38 of 112 (34%) of cases were re-classified (19 to pos. and 19 to neg.). By independent clinical laboratory interpretation of the results, 55 of 142 (39%) cases were re-classified (25 to pos. and 30 to neg.). A marked improvement was seen in concordance with the local tissue result after re-testing from 38% to 69% with the false positive rate decreasing from 18.8% to 3.6%. Re-classification of 17 (81%) original ‘false positive’ and 17 (35 %) original ‘false negative’ plasma results validates the original tissue results and appropriate collection and handling of plasma.
Conclusion:
Low concordance between original tissue and plasma EGFR status for the TKI sensitizing mutations observed in the Russian cohort from the IGNITE study was primarily due analytical issues in plasma test methodology. The contribution of the specific analytical process (extraction, testing or analysis) could not be determined. This follow-up study has been communicated back to the Russian laboratories resulting in the appropriate validation and proficiency programs being put in place to ensure quality plasma EGFR ctDNA testing.
