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P.A. Jänne
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MINI 05 - EGFR Mutant Lung Cancer 1 (ID 103)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:Y. Yatabe, R. Perez-Soler
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 2a-3b
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MINI05.08 - Comparison of the Efficacy of Dacomitinib v Erlotinib for NSCLC Pts with Del 19/L858R (ID 775)
16:45 - 18:15 | Author(s): P.A. Jänne
- Abstract
- Presentation
Background:
To date there have been limited randomized comparisons of EGFR tyrosine kinase inhibitors (TKI) in EGFR mutant NSCLC. Dacomitinib is a potent, irreversible EGFR inhibitor that demonstrated robust activity in a phase 2 study for patients with common activating EGFR mutations. Additionally, preclinical data suggests greater activity in patients with common EGFR activating mutations in exon 19 or 21. ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) each compared the clinical activity of dacomitinib (D) versus erlotinib (E) in advanced NSCLC including patients with common activating EGFR mutations; pooled results are presented.
Methods:
Patients (pts) with locally advanced/metastatic NSCLC were randomized following progression with 1 or 2 prior chemotherapy regimens to treatment with dacomitinib (D) (45 mg PO QD) or erlotinib (E) (150 mg PO QD). The Phase 2 study (A7471028) was open label while the Phase 3 ARCHER 1009 study was double-blind and double dummy. Archived tumor tissue, ECOG performance status (PS) of 0-2, adequate organ function and informed consent were required. Results of the two studies were previously reported individually. Analyses were performed by pooling patients with common EGFR activating mutations from both studies to compare efficacy of D versus E.
Results:
121 patients with any EGFR mutation were enrolled into the two studies with 1 patient randomized but not treated; 101 (53 on D) pts had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median PFS was 14.6 months (95%CI 9.0–18.2) for D and 9.6 months (95%CI 7.4–12.7) for E and unstratified HR 0.717 (95%CI 0.458–1.124) with 1-sided p=0.073. The median OS was 26.6 months (95%CI 21.6–41.5) for D and 23.2 months (95%CI 16.0–31.8) for E and unstratified HR 0.737 (95%CI 0.431–1.259) with 1-sided p=0.132. The corresponding pooled analyses were conducted separately in exon 19 and exon 21. The adverse-event profile did not differ between the activating mutation subset and the overall population. Figure 1
Conclusion:
Dacomitinib may be associated with an improved PFS and OS compared to Erlotinib in patients with exon 19/21 EGFR mutations. A prospective P3 study comparing D to another EGFR TKI in 1L EGFR mutated NSCLC is ongoing to verify these observations (NCT01774721).
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MINI 08 - Prognostic/Predictive Biomarkers (ID 106)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:T.E. Stinchcombe, N. Pavlakis
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 4a-4f
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MINI08.04 - VeriStrat® and Epidermal Growth Factor Receptor Mutation Status in a Phase 1b/2 Study of Cabozantinib +/- Erlotinib in Non-Small Cell Lung Cancer (ID 552)
16:45 - 18:15 | Author(s): P.A. Jänne
- Abstract
- Presentation
Background:
VeriStrat is a blood-based multivariate proteomic test that predicts response to second line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy in non-small cell lung cancer (NSCLC). We report a retrospective blinded analysis of VeriStrat classification in plasma samples from a phase 1b/2 trial of cabozantinib (C) +/- erlotinib (E) in metastatic NSCLC patients who had all progressed after benefiting from EGFR TKI therapy. Cabozantinib inhibits the MET/hepatocyte growth factor (HGF) pathway, and VeriStrat may be a surrogate marker for this pathway.
Methods:
Patients enrolled into phase 1b (1A:60 mg C+150 mg E, 2A:60 mg C+100 mg E, 3A:100 mg C+100 mg E, 4A:100 mg C+50 mg E, 2B:40 mg C+150 mg E) and phase 2 (Arm A:100 mg C, Arm B:100 mg C+50 mg E). EGFR mutation (EGFRm) status was tested on archival tissue and/or plasma when available. The primary objective was to determine if pre-treatment VeriStrat (VS) classification, good or poor, was prognostic for patients treated with cabozantinib +/- erlotinib. Kaplan-Meier method and log-rank test was used to compare progression-free survival (PFS) of VS-good v. VS-poor patients. Outcomes were stratified by EGFRm status (mutated v. wild type WT/unknown UNK).
Results:
Of 79 evaluable patients, 71 were classified as VS-good and 8 as VS-poor. 55.7% had an activating EGFRm (majority exon 19 del/exon 21 L858R) and 12.7% had UNK EGFRm status. There were no significant differences in patient characteristics between VeriStrat-groups. VS-good patients had a statistically improved PFS: VS-good 3.7 mo. (95% CI 3.5-5.4) v. VS-poor 1.9 mo. (95% CI 1.1-3.4), p=0.014. This was still true after excluding 14 patients who had received cabozantinib alone (p=0.005). There was no difference in PFS for VS-good patients when stratified by EGFRm status. There was also no difference in PFS for VS-poor patients with WT/UNK EGFR v. VS-good patients irrespective of EGFRm status. However, VS-poor patients with WT/UNK EGFR had improved PFS compared to VS-poor patients with an EGFRm (3.1 mo. v. 1.6 mo., HR 0.15, 95% CI 0.03-0.68).
Conclusion:
VeriStrat is a strong prognostic marker in this study. This study suggests cabozantinib neutralized the worse prognosis of VS-poor patients with WT/UNK EGFR. Given the heterogeneity of treatment dosing, the small number of VS-poor patients, and a high proportion of unknown EGFRm (including T790M) status, this analysis should be considered exploratory.
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MINI 09 - Drug Resistance (ID 107)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:L. Villaruz, J. Minna
- Coordinates: 9/07/2015, 16:45 - 18:15, 205+207
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MINI09.08 - Secondary C805S Mutation in HER2 Gene Confers Acquired Resistance to HER2 Kinase Inhibitors in HER2 Mutant Lung Cancer (ID 2181)
16:45 - 18:15 | Author(s): P.A. Jänne
- Abstract
- Presentation
Background:
Activating mutations in the HER2 kinase domain are detected in 2-4% of non-small cell lung cancers (NSCLC), and are oncogenic in both in vitro and in vivo models. Current clinical strategies to target mutant HER2 include the use of covalent HER2 inhibitors afatinib, dacomitinib and neratinib; all of which have limited single agent activity. We evaluated how drug sensitive models of HER2 mutant lung cancer develop acquired resistance in vitro to gain biological insights and to predict how acquired resistance may develop in the clinic.
Methods:
Murin Ba/F3 cells expressing duplication/insertion of four amino acids (YVMA) between codon 775 and 776 in exon 20 of HER2 gene (A775_G776insYVMA (insYVMA)) were exposed to N-ethyl-N-nitrosourea mutagenesis and expanded in the presence of neratinib and dacomitinib. Total RNAs were extracted from resistant clones and sequencing of the HER2 tyrosine kinase domain was performed. Drug resistance was confirmed with cell growth assays and western blotting.
Results:
Total 5 clones for Neratinib and 7 clones for Dacomitinib were expanded from each 300 wells. Sequencing analysis revealed that all resistant clones retained original insertion mutation and acquired same substitution of Cysteine to Serine change in codon 805 (C805S) in exon 20 of HER2 gene. This mutation is analogous to the EGFR C797S mutation that mediates resistance to 3[rd] generation EGFR inhibitors. Next, we generated Ba/F3 cells co-expressing activating mutations; insYVMA and a dacomitinib hypersensitive insertion mutation (insertion of three amino acids (WLV) after codon 774 with deletion of M774 (M774del insWLV (insWLV))), in cis with the C805S mutation. Cell growth assay revealed these double mutants were resistant to all three second generation inhibitors for EGFR family; neratinib, dacomitinib, and afatinib, compared to parental cells which only have activating mutation. They were also resistant to 3[rd] generation EGFR inhibitors; WZ40002 and AZD9291. Phosphorylation of HER2 was not completely inhibited by these drugs. Resistant cells showed moderate sensitivity to mTOR inhibitor; rapamycin alone. Combination treatment with afatinib and rapamycin effectively inhibited growth of these cells.
Conclusion:
The C805S secondary HER2 mutation results in acquired resistance to covalent HER2 inhibitors in HER2 mutant NSCLC. Our results provide insights into drug resistance mechanisms and help predict likely clinical mechanisms of resistance to HER2 targeted therapies in HER2 mutant NSCLC.
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MINI 16 - EGFR Mutant Lung Cancer 2 (ID 130)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 3
- Moderators:G.J. Riely, M.C. Garassino
- Coordinates: 9/08/2015, 16:45 - 18:15, Four Seasons Ballroom F3+F4
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MINI16.06 - AZD9291 in Pre-Treated T790M Positive Advanced NSCLC: AURA Study Phase II Extension Cohort (ID 943)
16:45 - 18:15 | Author(s): P.A. Jänne
- Abstract
- Presentation
Background:
AZD9291 is an oral, potent, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), selective for both EGFR-TKI-sensitizing (EGFRm) and T790M resistance mutations. The Phase I AURA study was a dose escalation/expansion study in patients with EGFRm positive advanced non-small cell lung cancer (NSCLC) who had progressed after EGFR‑TKI treatment. The 80 mg once daily (qd) dose was chosen for further evaluation in a Phase II extension cohort of the AURA study, and in an additional Phase II study (AURA2). Here we report efficacy and safety of AZD9291 from the AURA study Phase II extension cohort (NCT01802632) in patients pre-treated with EGFR-TKI and with centrally confirmed T790M positive advanced NSCLC.
Methods:
Eligible patients had measurable disease, World Health Organization performance status (WHO PS) 0 or 1, and acceptable organ function; stable brain metastases were allowed. A mandatory tumor sample was taken after disease progression on the most recent line of therapy, for prospective confirmation of T790M positive status by central laboratory testing (cobas™ EGFR Mutation Test). Patients received AZD9291 at 80 mg qd until disease progression. The primary endpoint was objective response rate (ORR) according to RECIST 1.1 (assessed by independent central review, ICR). Secondary objectives included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), investigator-assessed ORR, and safety. Planned enrollment was 175 patients to give an estimate of the ORR with 95% CI within ±8%. Data cut-off was January 9, 2015 after all patients should have undergone the second tumor assessment.
Results:
201 patients were dosed in the extension cohort of the study; two patients without measurable disease at baseline by ICR were excluded from the evaluable-for-response set. By central testing, EGFR mutation subtypes were: T790M, 98%; Ex19del, 71%; L858R, 25%; other, 3%. Median age was 62 years; female, 66%; Asian, 57%; WHO PS 0/1/2, 34%/66%/1%; second/≥third-line, 30%/70%. At the data cut-off, median treatment exposure was 4.9 months and 168 patients remain on treatment. ORR by ICR was 58% (115/199; 95% CI 51, 65) and DCR was 92% (95% CI 87, 95). ORRs were similar across lines of therapy (second-line, 59.0% [36/61] vs ≥third-line, 57.2% [79/138]). Investigator-assessed ORR was 68% (137/201; 95% CI 61, 75). Median DoR and median PFS have not been reached (maturity 2% and 21%, respectively). The most common all-causality adverse events (AEs) were diarrhea, 41% (0.5% Gr≥3) and grouped rash terms 37% (0.5% Gr≥3); 42 (21%) patients experienced Gr≥3 AEs. Interstitial lung disease grouped terms were reported in five (2.5%) patients, one of which was fatal (0.5%) and considered possibly causally related to AZD9291 by the investigator. Eight patients (4%) discontinued treatment due to an AE. Updated results from a later data cut-off will be available for presentation.
Conclusion:
In the AURA study Phase II extension cohort, AZD9291 80 mg qd demonstrates clinical activity, manageable tolerability, and a low discontinuation rate in patients with centrally confirmed EGFR T790M positive advanced NSCLC that has progressed on or after EGFR‑TKI treatment. These data provide further validation of the results from the Phase I study cohorts.
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MINI16.07 - AZD9291 in Treatment-Naïve EGFRm Advanced NSCLC: AURA First-Line Cohort (ID 1232)
16:45 - 18:15 | Author(s): P.A. Jänne
- Abstract
- Presentation
Background:
AZD9291 is an oral, potent, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) selective for both EGFR-sensitizing (EGFRm) and T790M resistance mutations. It has shown anticancer activity and manageable tolerability in patients with EGFRm advanced NSCLC that had progressed after EGFR‑TKI treatment.
Methods:
In this first-line expansion cohort (AURA, NCT01802632), patients received AZD9291 at 80 or 160 mg/day, in sequential dose groups. EGFRm status was determined locally and/or by central testing using the cobas EGFR Mutation Test. Other inclusion criteria included measurable disease, World Health Organization performance status (WHO PS) 0 or 1, and acceptable organ function; stable brain metastases were allowed. Safety, tolerability, and anticancer activity were assessed in these cohorts, to evaluate AZD9291 in the first-line treatment setting. The data cut-off was December 2, 2014.
Results:
Sixty treatment-naïve patients were enrolled; 30 patients in each dose group (80 or 160 mg/day). By central testing, EGFR mutation subtypes were: L858R 40%; exon 19 deletion, 37%; other EGFR-sensitizing mutations, 3%; and T790M, 8%. Baseline median age was 63.5 years; 25% of patients were male; 57%/43% had WHO PS 0/1, respectively; 72% were Asian and 23% Caucasian. Median treatment exposure at the 80 and 160 mg dose levels was 260 and 171 days, respectively. Fifty-two out of 60 patients remained on treatment at the data cut-off. Anticancer activity of AZD9291 is shown in Table 1. One-third (33%) of patients experienced Grade ≥3 adverse events; two patients had Grade 3 diarrhea and one patient had Grade 3 skin rash. New data from a 2015 data cut of the AURA first-line expansion will be available for presentation.Table 1. Anticancer activity findings in AURA first-line expansion
Endpoint Finding Objective response rate: Overall 70% (95% CI 57, 81) AZD9291 80 mg/160 mg 60%/80% Disease control rate: Overall 97% (95% CI 89, 100) AZD9291 80 mg/160 mg 93%/100% Progression-free survival: Median Not yet reached 3-month/6-month 93%/87% Events to date 7/60 (12% mature)
Conclusion:
AZD9291 has a manageable tolerability profile and is associated with promising anticancer activity in treatment-naïve patients with EGFRm advanced NSCLC. A Phase III study (FLAURA, NCT02296125) has been initiated to assess the efficacy and safety of AZD9291 in comparison with a standard-of-care EGFR-TKI (gefitinib or erlotinib) in the first-line setting.
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MINI16.09 - Design, Execution, and Preliminary Biomarker Results from Paired Tumor Biopsy Cohorts of the AZD9291 AURA Trial (ID 941)
16:45 - 18:15 | Author(s): P.A. Jänne
- Abstract
Background:
Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) exhibits sensitivity to EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib; however, acquired resistance eventually develops in most patients. The most common mechanism of TKI resistance is a second-site mutation in the EGFR kinase domain, T790M. AZD9291 is an oral, potent, irreversible EGFR-TKI with potency against both T790M resistance and sensitizing EGFR mutations. In the ongoing Phase I AURA study (NCT01802632), AZD9291 induced durable responses in patients with acquired resistance to EGFR-TKIs. We report results of paired biopsy cohorts of the AURA trial, reviewing modulation of key molecular biomarkers of AZD9291 activity in patient tumor samples.
Methods:
Two cohorts of patients on the AURA trial were consented for collection of paired tumor biopsies. These patients had a pre-study tumor biopsy with T790M positive tumor status confirmed by central laboratory EGFR testing (Cobas™ EGFR Mutation Test). Following 8 to 15 days of once daily AZD9291 treatment (80 or 160 mg), a post-dose tumor biopsy was obtained. Baseline and post-dose tumor tissue was processed for routine histology and pathologic evaluation. More than 100 viable tumor cells per sample were required for subsequent biomarker scoring. Formalin-fixed paraffin-embedded tumor biopsies were profiled by immunohistochemistry with a suite of key pathway and tumor-relevant markers (phospho[p]-EGFR, pERK, pAKT, pS6, PD-L1, CD8). Matching plasma pharmacokinetic samples were also obtained for PK-PD correlations.
Results:
As of February 2015, 58 potential patients with an evaluable baseline biopsy were identified as candidates for post-dose biopsy collection. Sixteen of these patients did not proceed to an on-study biopsy as the identified lesions had regressed too substantially or were no longer considered suitable for re-biopsy, one patient was medically excluded from re-biopsy, and one patient’s sample was not available. In total, 40 patients supplied matched pre- and on-treatment biopsies. As of March 2015, paired tumor samples were available for QC from 26 of these 40 patients. Ten of these 26 biopsy specimens subsequently failed QC due to inadequate tumor content, leaving 16 paired tumor samples available for biomarker analyses, of which five have thus far been evaluated. AZD9291 treatment resulted in the inhibition of EGFR pathway components in the majority of post-treatment tumor biopsies. Tissue biomarker analyses are ongoing and updated data on evaluable biopsy pairs will be reported at the time of the congress.
Conclusion:
The completion of a paired biopsy cohort within the AURA trial was challenging due to the rapid onset of anti-tumor effects of AZD9291. Approximately 29% (17/58) of potentially eligible patients were unsuitable for the post-dose biopsy procedure due to tumor regression and 38% (10/26) of available post-dose biopsies were found to contain too little tumor for analysis. In the evaluable tumor pairs, pharmacodynamic modulation of the EGFR pathway was evident. Further biomarker analyses, including evidence of modulation of immune system markers, may help inform future combination strategies.
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ORAL 17 - EGFR Mutant Lung Cancer (ID 116)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:P. Meldgaard, E. Felip
- Coordinates: 9/08/2015, 10:45 - 12:15, Four Seasons Ballroom F3+F4
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ORAL17.07 - Mechanisms of Acquired Resistance to AZD9291 in EGFR T790M Positive Lung Cancer (ID 1365)
10:45 - 12:15 | Author(s): P.A. Jänne
- Abstract
Background:
AZD9291 is an irreversible, mutant-selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) developed to have potency against both EGFR-sensitizing mutations and T790M. In the ongoing Phase I study of AZD9291 (AURA, NCT01802632), the response rate in patients with T790M positive lung cancer with disease progression on previous EGFR-TKI was >60%, with a preliminary median progression-free survival of >10 months. The molecular mechanisms underlying acquired resistance to AZD9291 are currently under investigation.
Methods:
Plasma genotyping was performed on patients from AURA who had progressed on AZD9291 if they had detectable T790M pre-AZD9291, as assessed by tumor or plasma genotyping, and if they had plasma collected at progression available for analysis. Cell-free DNA (cfDNA) was extracted from plasma taken at progression. Droplet digital PCR (ddPCR) was performed for EGFR exon 19 deletions, L858R, T790M, and C797S. For further exploration, next-generation sequencing (NGS) of an amplicon panel was performed on available progression cfDNA. Lastly, targeted NGS was performed on available resistance biopsy specimens.
Results:
Plasma specimens were available following disease progression on AZD9291 from 40 patients with tumors positive for T790M through tumor (33) or plasma genotyping (7). Twenty-six progression cfDNA specimens were positive for an EGFR-sensitizing mutation by ddPCR, and were deemed eligible for initial resistance analysis. Of these, 12 (46%) had no detectable T790M in plasma despite presence of the EGFR-sensitizing mutation, suggesting overgrowth of an alternate resistance mechanism. Seven patients had detectable C797S on ddPCR (27%), all with detectable T790M; of 14 with detectable T790M at resistance, C797S was only detected with EGFR exon 19 deletions (7/9) and not L858R (0/5, p=0.02). Plasma NGS was performed on 12 cases with acquired resistance that were T790M positive pretreatment. Exon 19 deletion/T790M/C797S were detected in four cases, with two of these harboring two different DNA mutations encoding for C797S. One case lost T790M and exhibited HER2 copy number gain (6.3 copies); a tumor biopsy from a separate case underwent aCGH at Institute Gustave Roussy and was also found to have focal HER2 amplification with loss of T790M. Targeted NGS was performed on resistance biopsies from a total of 10 patients from four centers with T790M positive biopsies pre-AZD9291. Six cases maintained T790M, with three harboring exon 19 del/T790M/C797S. In four cases with loss of T790M, one harbored BRAF V600E and one harbored PIK3CA E545K.
Conclusion:
Complementary genomic analysis of plasma and tumor DNA provides insight into the diverse molecular mechanisms of acquired resistance to AZD9291 in EGFR-mutant lung cancer. Our studies show that a majority of cases maintained T790M at resistance, at times acquiring a new C797S mutation in those with EGFR exon 19 deletion. Loss of T790M at progression may be mediated by overgrowth of cells harboring HER2 amplification, BRAF V600E, or PIK3CA mutations. These data highlight the need for investigation of combination therapies to effectively prevent or treat the complexity of drug resistance in EGFR-mutant lung cancer.
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ORAL 38 - Liquid Biopsies (ID 147)
- Event: WCLC 2015
- Type: Oral Session
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:M.S. Tsao, J. Wang
- Coordinates: 9/09/2015, 16:45 - 18:15, Mile High Ballroom 2a-3b
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ORAL38.01 - A Prospective Study of Rapid Plasma Genotyping Utilizing Sequential ddPCR and NGS in Newly Diagnosed Advanced NSCLC Patients (ID 935)
16:45 - 18:15 | Author(s): P.A. Jänne
- Abstract
- Presentation
Background:
Plasma genotyping of cell-free DNA (cfDNA) has the potential to allow for noninvasive genotyping while avoiding the inherent shortcomings of tissue genotyping and repeat biopsies. We have developed a quantitative droplet digital PCR (ddPCR)-based plasma genotyping assay capable of detecting common EGFR and KRAS mutations in NSCLC (Oxnard et al., CCR 2014). Although rapid and highly specific, this assay lacks the ability to both multiplex and detect complex genomic alterations such as rearrangements. In this prospective study, we evaluate the test characteristics of ddPCR combined with plasma next-generation gene sequencing (NGS) as a new paradigm for plasma genotyping.
Methods:
Patients with newly diagnosed advanced NSCLC were eligible. All patients were required to have a biopsy available or planned for tissue genotyping which was used for gold standard comparison. Patients underwent an initial blood draw and immediate plasma ddPCR for EGFR exon 19 del/L858R and KRAS G12X. A subset of patients additionally underwent plasma NGS using a unique probe set designed by our group to detect rearrangements and mutations in 12 genes (EGFR, KRAS, ALK, ROS1, BRAF, RET, NRAS, ERBB2, MET, MEK1, PIK3CA and p53). This plasma NGS assay utilized a novel bias corrected NGS which minimizes off-target reads (Resolution Bio) performed on a desktop MiSeq platform. Test turnaround time (TAT) was measured in business days from date of blood draw until test reporting.
Results:
120 patients with newly diagnosed advanced NSCLC have been enrolled and 94 have completed tissue and plasma genotyping. Tumor genotype included 25 EGFR exon 19/L858R mutants, 17 KRAS G12X mutants, 24 rare genotypes and 15 others. Median TAT for plasma ddPCR was 3 days (range 1-5). Specificity of plasma ddPCR was 99% for EGFR exon 19 del/L858R (68/69) and 100% for KRAS (77/77). Sensitivity of plasma ddPCR was 76% for EGFR exon 19 del/L858R (19/25) and 71% for KRAS (12/17). Plasma NGS is ongoing with testing completed on 11 patients with a known tumor genotype. 8 had a genotype detected on plasma NGS: 2 ALK rearrangements, 1 ROS1 rearrangement, 1 RET rearrangement, an EGFR G719A mutation, a KRAS G12C and a combined KRAS G12C/PIK3CA mutation - all matched the tumor genotype. Preliminary plasma NGS turnaround time ranged from 5-10 business days.
Conclusion:
Rapid plasma genotyping using sequential plasma ddPCR (1-5 day TAT) followed by plasma NGS (5-10 day TAT) represents a new paradigm for noninvasive plasma genotyping. This approach capitalizes on the use of rapid ddPCR for common targetable mutations and the ability of plasma NGS using an augmented MiSeq platform to multiplex and detect complex alterations. This new model for plasma genotyping uses testing platforms that can readily be employed in most molecular pathology laboratories allowing for widespread adoption.
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PLEN 03 - Science Drives Lung Cancer Advances (ID 52)
- Event: WCLC 2015
- Type: Plenary
- Track: Plenary
- Presentations: 1
- Moderators:T. Mitsudomi, T. Mok
- Coordinates: 9/09/2015, 08:15 - 09:45, Plenary Hall (Bellco Theatre)
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PLEN03.03 - Molecular Mechanisms of Drug Resistance (ID 2045)
08:15 - 09:45 | Author(s): P.A. Jänne
- Abstract
Abstract not provided
