Resected EGFR Research Articles

1215P United Kingdom (UK) real world study of adjuvant osimertinib in resected EGFR mutated lung cancer

1215P United Kingdom (UK) real world study of adjuvant osimertinib in resected EGFR mutated lung cancer

Early-Stage Non-Small Cell Lung Cancer: New Challenges with Immune Checkpoint Blockers and Targeted Therapies.

The recent advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockers (ICBs) in early-stage non-small cell lung cancer (NSCLC) has dramatically modified treatment strategies by improving the prognosis in this setting. Osimertinib and alectinib, both TKIs, have shown significant improvements in outcomes for patients with resected EGFR- and ALK-positive NSCLC, respectively, changing the standard of care in these subgroups. More recently, the LAURA trial showed the efficacy of osimertinib after chemoradiotherapy in patients with unresectable stage III NSCLC harboring EGFR mutations. Numerous trials are still ongoing to investigate neoadjuvant/perioperative TKIs in several oncogene-driven NSCLC. In addition, several ICBs have been tested and approved as adjuvant (atezolizumab and pembrolizumab), neoadjuvant (nivolumab), and perioperative treatments (pembrolizumab) for patients with resectable early-stage NSCLC. Despite these advances, many challenges remain regarding the use of TKIs and ICBs in this setting, including the optimal duration of adjuvant TKI or induction ICB therapy, the role of minimal residual disease to identify patients at high-risk of disease relapse and to guide adjuvant treatment decisions, and the role of adjuvant chemotherapy in resected oncogene-driven NSCLC. Furthermore, potential predictive biomarkers for efficacy are needed to eventually intensify the entire perioperative strategies. This review aims to summarize and discuss the available evidence, the ongoing trials, and the challenges associated with TKI- and ICB-based approaches in early-stage NSCLC.

The efficacy of postoperative radiotherapy in resected pⅢA-N2 EGFR mutant and wild-type lung adenocarcinoma

The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1months; p= 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p= 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2months; p= 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p= 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

84 National Real World Study of Adjuvant Osimertinib in Resected EGFR Mutated Lung Cancer

84 National Real World Study of Adjuvant Osimertinib in Resected EGFR Mutated Lung Cancer

EE72 A Cost-Effectiveness Analysis of Adjuvant Osimertinib in Patients with Resected EGFR Mutation-Positive Non-Small Cell Lung Cancer in Portugal

EE72 A Cost-Effectiveness Analysis of Adjuvant Osimertinib in Patients with Resected EGFR Mutation-Positive Non-Small Cell Lung Cancer in Portugal

Brief Report: Circular Runt-related transcription factor (circRUNX1) as potential biomarker for cancer recurrence in EGFR mutation-positive surgically resected NSCLC

IntroductionAs recently evidenced by the ADAURA trial, most patients with stages IB to IIIA of resected EGFR-mutant lung adenocarcinoma benefit from osimertinib as adjuvant therapy. Nevertheless, predictive markers of response and recurrence are still an unmet need for more than 10% of these patients. Some circular RNAs (circRNAs) have been reported to play a role in tumor growth and proliferation. In this project, we studied circRNA expression levels in formalin-fixed, paraffin-embedded lung tumor samples to explore their biomarker potential and develop a machine learning (ML)-based signature that could predict the benefit of adjuvant EGFR tyrosine kinase inhibitors in patients with EGFR-mutant NSCLC. MethodsPatients with surgically resected EGFR mutant-positive, stages I to IIIB NSCLC were recruited from February 2007 to December 2015. Formalin-fixed, paraffin-embedded tumor samples were retrospectively collected from those patients with a follow-up period of more than or equal to 36 months (N = 76). Clinicopathologic features were annotated. Total RNA was purified and quantified prior nCounter processing with our circRNA custom panel. Data analysis and ML were performed taking into consideration circRNA expression levels and recurrence-free survival (RFS). RFS was defined from the day of surgery to the day when recurrence was detected radiologically or the death owing to any cause. ResultsOf the 76 patients with EGFR mutation-positive NSCLC included in the study, 34 relapsed within 3 years after resection. The median age of the relapsing cohort was 71.5 (range: 49–89) years. Most patients were nonsmokers (n = 21; 61.8%) and of female sex (n = 21; 61.8%). Most cases (n = 17; 50%) presented an exon 21 mutation, whereas 15 and four patients had an exon 19 and exon 18 mutation, respectively. Differential expression analysis revealed that circRUNX1, along with circFUT8 and circAASDH, was up-regulated in relapsing patients (p < 0.05 and >2 fold-change). A ML-based circRNA signature predictive of recurrence in patients with EGFR mutation-positive NSCLC, comprising circRUNX1, was developed. Our final model including selected 6-circRNA signature with random forest algorithm was able to classify relapsing patients with an accuracy of 83% and an area under the receiver operating characteristic curve of 0.91.RFS was significantly shorter not only for the subgroup of patients with high versus low circRUNX1 expression but also for the group classified as recurrent by the ML circRNA signature when compared with those classified as nonrecurrent. ConclusionsOur findings suggest that circRUNX1 and the presented ML-developed signature could be novel tools to predict the benefit of adjuvant EGFR tyrosine kinase inhibitors with regard to RFS in patients with EGFR-mutant NSCLC. The training and validation phases of our ML signature will be conducted including bigger independent cohorts.

Comparative Analysis of the Prognostic Significance of IDH,TERT, EGFR and MGMT Status in Patients with Adult Non-H3-Altered Grade 4 Gliomas: A Prospective Cohort Study

IntroductionGliomas continue to have a dismal prognosis. A myriad of genetic alterations has been described in this subset of tumors over the last decades. The integrative interpretation of the biomarker constellation for individual patients remains unclear. This study aims to evaluate the impact of some known genetic factors as prognostic biomarkers in grade 4 gliomas. MethodsAdult non-H3-altered grade 4 gliomas who underwent maximal safe resection accompanied by adjuvant therapy were successively enrolled since January 2019 till January 2021. Patient data were documented preoperatively and during the follow-up visits. The genetic profiling of the tumors included IDH-1 and IDH-2 mutation, MGMT promoter methylation rate, EGFR gene amplification and TERT promoter (TERTp) mutation. ResultsMean Overall survival (OS) and Progression-free survival (PFS) were 14.45±5.13 months (3-24 months) and 10.66±4.87 months respectively. TERTp-mutant group had a significantly lower OS (10.9 vs 15.9) and PFS (6.9 vs 12.3) than TERTp wildtype group. In the TERT-mutant group, those with concomitant IDH wildtype tumor had higher OS and PFS, comparable to those with both TERTp and IDH wildtype tumors. In multivariate analysis, IDH mutation and TERTp wildtype status were predictive of longer OS and PFS. While IDH and absence of TERTp mutation were associated with KPS>80 across the follow-ups, their predictive values were inferior to preoperative KPS scores. ConclusionTERTp mutation and IDH-wildtype status were associated with worse OS and PFS and lower follow-up KPS score in surgically resected gliomas, while MGMT and EGFR status did not have considerable prognostic value in this study.

Differential expression analysis of circRUNX1 in patients with early resected EGFR-mutant NSCLC.

8529 Background: In the ADAURA study, patients with stage IB-IIIA of resected EGFR mutated lung adenocarcinoma receiving adjuvant osimertinib had a 2-year survival of 89% versus 52% in the placebo group (p&lt;0.001), however, predictive markers of response and recurrence are still needed. Circular RNA (circRNA) is a type of RNA which forms a covalently closed continuous loop. Some circRNAs have been reported as essential for tumor cell proliferation through functions distinct from the canonical linear RNA. In this project, we studied circRNA expression levels in formalin-fixed paraffin-embedded (FFPE) lung tumor samples in order to explore potential biomarkers that could predict the benefit of adjuvant EGFR TKIs in EGFR-mutant NSCLC patients. Methods: FFPE tumor samples from patients with EGFR-mutant, stage I-IIIB NSCLC (n=79) were collected. RNA was purified using the High Pure FFPET RNA Isolation Kit (Qiagen) and quantified by Nanodrop 2000 (Thermo Scientific). A total of 250 ng of RNA were subjected to overnight hybridization and downstream nCounter processing (NanoString) following manufacturer’s instructions for our circRNA custom panel. Differential expression analysis was performed using Excel (Microsoft) and Prism GraphPad (Dotmatics) software. Results: Analysis of the 79 samples included in the study shown a cluster of 3 circRNAs significantly upregulated (p&lt;0.05 and &gt;2 fold-change) in EGFR mutation-positive NSCLC relapsing withing the 36 months after resection, including circRUNX1, circFUT8 and circAASDH. Disease-free survival (DFS) was significantly shorter for the subgroup of patients with high versus low circRUNX1 expression. Additional multivariate analysis identified circRUNX1 expression and tumor stage as the only statically significant prognostic factors (circRUNX1 hazard ratio = 4.480, confidence interval = 2.172-9.239, P &lt; 0.001; pathological stage hazard ratio = 2.237, confidence interval = 1.183- 4.231, P = 0.008). Conclusions: CircRUNX1 could be a novel biomarker to predict the benefit of adjuvant EGFR TKIs with regards to DFS in EGFR-mutant resected NSCLC patients.

Evaluation of Cost-Effectiveness of Adjuvant Osimertinib in Patients with Resected EGFR Mutation-Positive Non-small Cell Lung Cancer.

For many patients with resected epidermal growth factor receptor mutation-positive (EGFRm) non-small cell lung cancer (NSCLC), current standard of care (SoC) is adjuvant chemotherapy; however, disease recurrence remains high. Based on positive results from ADAURA (NCT02511106), adjuvant osimertinib was approved for treatment of resected stage IB‒IIIA EGFRm NSCLC. The aim was to assess the cost-effectiveness of adjuvant osimertinib in patients with resected EGFRm NSCLC. A five-health-state, state-transition model with time dependency was developed to estimate lifetime (38 years) costs and survival of resected EGFRm patients treated with adjuvant osimertinib or placebo (active surveillance), with/without prior adjuvant chemotherapy, using a Canadian Public Healthcare perspective. Transitions between health states were modeled using ADAURA and FLAURA (NCT02296125) data, Canadian life tables, and real-world data (CancerLinQ Discovery®). The model used a 'cure' assumption: patients remaining disease free for 5 years after treatment completion for resectable disease were deemed 'cured.' Health state utility values and healthcare resource usage estimates were derived from Canadian real-world evidence. In the reference case, adjuvant osimertinib treatment led to a mean 3.20 additional quality-adjusted life-years (QALYs; (11.77 vs 8.57) per patient, versus active surveillance. The modeled median percentage of patients alive at 10 years was 62.5% versus 39.3%, respectively. Osimertinib was associated with mean added costs of Canadian dollars (C$)114,513 per patient and a cost/QALY (incremental cost-effectiveness ratio) of C$35,811 versus active surveillance. Model robustness was demonstrated by scenario analyses. In this cost-effectiveness assessment, adjuvant osimertinib was cost-effective compared with active surveillance for patients with completely resected stage IB‒IIIA EGFRm NSCLC after SoC.

Economic evaluations of adjunctive osimertinib treatment in surgically resected epidermal growth factor receptor positive (EGFR+) non-small cell lung cancer (NSCLC): Analysis for stage 1B disease.

e20502 Background: Patients with stage 1B non-small cell lung cancer (NSCLC) who receive surgical resection are at continued risk of disease recurrence and death after the surgery. Osimertinib, a tyrosine kinase inhibitor indicated for epidermal growth factor receptor positive (EGFR+) NSCLC, has been used post-operatively as adjunctive therapy to improve clinical outcomes in surgically resected EGFR+ stage 1B NSCLC. We evaluated the cost effectiveness/utility of adjunctive osimertinib treatment post-surgically in stage 1B. Methods: A two state partitioned survival model with disease free survival (DFS) and disease recurrence or death was specified (US payer perspective). Kaplan-Meier DFS curves were fitted to parametric functions. A 5 year time horizon was adopted and a 3% discount rate was applied to costs and utilities after year 1. Wholesale acquisition costs for treatments were sourced from Redbook, adverse event costs (grade 3/4; all grades for immunotherapy related AEs) utilized published data, and monitoring costs were based on Physician Fee Schedules (US $2021). We estimated incremental costs, DFS life years (DFSLY), and DFS quality adjusted life years (DFSQALY). Based on DFSLY and DFSQALY gained (g), incremental cost effectiveness/utility ratios (ICER/ICUR) were determined in base case analyses (BCA) and probabilistic sensitivity analyses (PSA). Results: Exponential regression was utilized to extrapolate the osimertinib DFS Kaplan-Meier curve, while Weibull regression was applied for extrapolation of the placebo DFS curve. Shown in the table below, the BCA (PSA) revealed incremental cost of $774,710 ($775,941) and ncremental DFSLY of 0.813 (0.954), yielding an ICER of $952,797/DFSLYg ($813,162/DFSLYg); and incremental DFSQALY of 0.576 (0.676), yielding an ICUR of $1,345,340/DFSQALYg (1,147,793/DFSQALYg). Conclusions: In surgically resected stage 1B EGFR+ NSCLC, the model estimated incremental benefits of 0.813 (0.954) LYg and 0.576 (0.676) QALYg, however at marked incremental cost. As adjunctive osimertinib treatment is indicated in EGFR+ NSCLC disease stages 2 and 3A, the present stage 1B cost effectiveness/utility results should be compared to those for stages 2 and 3A.[Table: see text]

Economic evaluations of adjunctive osimertinib treatment in surgically resected epidermal growth factor receptor-positive (EGFR+) non-small cell lung cancer (NSCLC): Analysis for stage 2 disease.

e20506 Background: Following surgical resection, patients with NSCLC require monitoring due to the risk of recurrence. Studies have demonstrated the clinical benefit of osimertinib, a tyrosine kinase inhibitor, as adjunctive therapy in surgically resected EGFR+ NSCLC, including in stage 2 disease. We performed a cost effectiveness/utility analysis of adjunctive osimertinib therapy in stage 2 disease following surgical resection. Methods: A two state partitioned survival model differentiating disease free survival (DFS) from disease recurrence and death was specified (US payer perspective). Parametric functions were fit to digitized overall survival (OS) and DFS curves. A 5 year time horizon was specified, with a 3% discount rate applied to costs and utilities beyond year 1. Costs of treatment (wholesale acquisition cost), adverse events (grade 3/4 except all grades for immunotherapy related AEs), and monitoring were sourced from, respectively, Redbook, literature, and Physician Fee Schedules (US $2021). DFS life years (DFSLY) and quality adjusted life years (DFSQALY), incremental cost effectiveness/utility ratios (ICER/ICUR) in terms of DFSLY and DFSQALY gained (g) were estimated in base case analyses (BSA) and probabilistic sensitivity analyses (PSA). Results: Exponential regression was used to extrapolate osimertinib and placebo Kaplan-Meier curves. As detailed below, in BCA (PSA) the incremental cost of osimertinib over placebo was $778,315 ($778,202). The incremental DFSLY was 1.740 (1.738), which yielded ICER of $447,349/DFSLYg ($447,768/DFSLYg). The incremental DFS QALY was 1.234 (1.232), yielding ICUR of $630,910/DFSQALYg ($631,498/DFSQALYg). Conclusions: As to disease recurrence in stage 2 surgically resected EGFR+ NSCLC, our model associated adjunctive osimertinib therapy with incremental clinical gains of 1.740 (1.738) DFSLY and 1.234 (1.232) DFSQALY compared to placebo, however at marked incremental cost. As adjunctive osimertinib treatment is indicated in EGFR+ NSCLC disease stages 1B and 3A, the present stage 2 cost effectiveness/utility results should be compared to those for stages 1B and 3A.[Table: see text]

Economic evaluations of adjunctive osimertinib treatment in surgically resected epidermal growth factor receptor positive (EGFR+) non-small cell lung cancer (NSCLC): Analysis for stage 3A disease.

e20505 Background: Patients with surgically resected EGFR+ NSCLC remain at risk of recurrence after surgery. Osimertinib, a tyrosine kinase inhibitor, had been assessed clinically as adjunctive therapy in surgically resected EGFR+ NSCLC including stage 3A. We conducted a cost effectiveness/utility analysis of adjunctive osimertinib therapy in stage 3A surgically resected EGFR+ NSCLC. Methods: We specified a two state partitioned survival model of disease free survival (DFS) versus disease recurrence and death in a), with a 5 year time horizon (US payer perspective). DFS and overall survival curves were extrapolated per parametric functions. A 3% discount rate was utilized to costs and utilities beyond year 1. Costs of therapies (wholesale acquisition cost), adverse events (AE; grade 3/4; all grades for immunotherapy related AEs), and monitoring costs were based on Redbook, publications, and Physician Fee Schedules, respectively (US $2021). Costs, DFS life years (DFSLY) and DFS quality adjusted life years (DFSQALY) were used to determine the incremental cost effectiveness/utility ratios (ICER/ICUR) of the additional cost needed to gain (g) a DFSLY and DFSQALY in base case (BSA) and probabilistic sensitivity analyses (PSA). Results: Exponential regression was used to extrapolate the Kaplan-Meier curves of osimertinib and placebo,. As shown in the table, the BCA (PSA) estimated the incremental cost at $669,369 ($670,274). The incremental DFSLY was 1.895 (1.899), yielding ICER of $353,125/DFSLYg ($352,963/DFSLYg). The incremental DFS QALY was 1.35, yielding an ICUR of $497,905/DFSQALYg ($497,676/DFSQALYg). Conclusions: In stage 3A surgically resected EGFR+ NSCLC, adjunctive osimertinib therapy showed incremental benefits of 1.895 (1.899) DSFLYg and 1.344 (1.349) QALYg compared to placebo, however at marked incremental cost. As adjunctive osimertinib treatment is indicated in EGFR+ NSCLC disease stages1B and 2, the present stage 3A cost effectiveness/utility results should be compared to those for stages 1B and 2.[Table: see text]

Natural history of curatively resected stage IB-IIIA EGFR mutation (+) NSCLC: Clinicopathologic and molecular prognostic factors (ROOT-EGFR-ADJ).

8529 Background: Surgery is the primary therapy for patients with early-stage NSCLC. However, five-year recurrence rates were 45%, 62%, and 76% for pathologic stage (pStage) IB, II, and III respectively. In the ADARUA study, adjuvant osimertinib significantly improved DFS in patients with completely resected EGFR mutation (+) NSCLC. Though marked improvement of DFS is encouraging, OS is not mature yet and several questions remain unanswered; Does this DFS benefit translate to cure? Do all patients need to receive adjuvant Osiemrtinib? In order to address these questions we reviewed the clinical records of pStage IB-IIIA EGFR mutant NSCLC. Methods: From January 2008 and August 2020, total 2,340 patients with pStage IB-IIIA, non-SQ NSCLC underwent curative surgery at Samsung Medical Center. Using innovative in-house algorithm to retrieve medical big data-based cohort called ROOT (Realtime autOmetically updated data warehOuse in healTh care) detailed clinical data were analyzed to investigate any prognostic factors of recurrence. In order to identify any molecular prognostic factors, we did a comprehensive genomic analysis (WTS/WES)in a subset of patients with matched case-control. Results: Total 1,811 patients with pStage IB-IIIA, non-SQ EGFR mutation (+) NSCLC were included (367 patients : no EGFR mutation test). Median follow-up duration was 38.8 (range: 0.5 -156.2). Patient demographics; Deletion 19 was 52.7%, L858R was 47.3%. Female was 64.7% and never smoker was 72%. Stage IB, IIA, IIIA was 50.4%, 26.5%, and 23.2%. Among them, 6.7% of pStage IB, 72.8% of pStage II, and 88.7% of pStage IIIA received adjuvant chemotherapy. Median DFS were 74.0 months (95% CI 63.2-84.8), 48.6 months (95% CI: 40.2-57.0), and 22.4 months (95%: 19.5-25.3) for pStage IB, II, and IIIA, respectively. The median OS were 132.1 months (95% CI: 101.3-162.8), 124.3 months (95% CI: 61.8-186.9), and 82.1 months (95% CI: 71.2-93.1) for pStage IB, II, and IIIA, respectively. In univariate analysis, pStage, poorly differentiation, histologic subtype (micropapillary, solid), lymphatic invasion, vascular invasion, and pleural invasion were related with high recurrence rate statistically. In multivariate analysis, pStage, vascular invasion, and pleural invasion were related with recurrence statistically. To detect molecular factors, 76 patients performed the matched case -control (included pStage, type of EGFR mutation, and sex) analysis (WES/WTS). Conclusions: This study showed that the median DFS of pStage II-IIIA EGFR mutation (+) NSCLC was 31.9 months. With approximately 55% of patients with pStage II-IIIA EGFR mutation (+) NSCLC experienced recurrence at the 3rd year, we need to find the appropriate subset who need 3-year adjuvant osimertinib by comprehensive predictive marker for cure. Updated and detail exploratory biomarker outcome will be presented at the annual meeting.

Cost evaluation of adjunctive osimertinib use in resected epidermal growth factor receptor-positive non-small cell lung cancer.

8525 Background: About 30% of patients with epidermal growth factor receptor positive (EGFR+) non small cell lung cancer (NSCLC) are eligible for surgical resection. Osimertinib, a first line therapy for advanced EGFR+ NSCLC (stages 1B, 2, 3A), has shown clinical efficacy compared to placebo as an adjunctive therapy post resection. We evaluated the cost effectiveness/utility of this regimen. Methods: A two health state Markov model was built (disease free vs. disease recurrence or death). Disease free survival (DFS) curves were digitized and fitted to exponential function. 3 year timeline as patients received osimertinib for 3 years in published data. US payer perspective and 3% discount rate were applied. Drug costs were per Redbook whole acquisition cost and monitoring costs were from published data (US$ 2020). No adverse events &gt; 5% were reported hence none were included. Life years (LY) and quality adjusted life years (QALY) were estimated for each stage. Incremental cost-effectiveness and utility ratios (ICER/ICUR) for LY and QALY gained were estimated in base case (BCA) and probabilistic sensitivity analyses (PSA). Results: Shown in the table are BCA and (PSA) results. Using LY as outcome, for stage 1B, incremental DFSLY of 0.40 (0.39) and incremental cost of $500,782 ($501,034) yielded an ICER/DFSLYG of ̃$1.3 million (M) (̃$1.2 M). For stage 2, incremental DFSLY of 0.79 (0.79) and incremental cost of $503,144 ($503,092) resulted in an ICER/DFSLYG of $636,913 ($638,278). For stage 3A, incremental of DFSLY of 0.18 (0.07) and incremental cost of $322,356 ($293,377) yielded an ICER/DFSLYG of ̃$1.2 M (̃1.2 M). The incremental costs are the same for QALY outcomes. Using QALY as outcome, for stage 1B, incremental of DFSQALY of 0.26 (0.27) yielded an ICUR/DFSQALY of ̃$1.9 M. In stage 2, incremental DFSQALY of 0.53 (0.53) resulted in an ICUR/DFSQALY of $950,616 ($952,654). For stage 1C, incremental DFSQALY of 0.18 (0.07) yielded an ICUR/DFSQALY of ̃$1.8 M (̃$3.7 M). Conclusions: The ICERs and ICURs indicate that cost effectiveness varies markedly across stages of disease. Stage 2 showed the lowest cost to outcome association. In general, the cost burden of adjunctive maintenance therapy with osimertinib in resected EGFR+ NSCLC is substantial relative to the observed clinical benefit. The incremental benefit of osimertinib in stage 2b is more evident than the ones in 1B and 3A.[Table: see text]

Prevalence of EGFR mutation testing in early-stage lung cancer: Implications of the ADAURA trial for clinical practice.

e20507 Background: It is reported that about 20% of patients with resected NSCLC adenocarcinoma harbor an EGFR driver mutation in the United States. Up to the recent approval of osimertinib in the adjuvant setting for resected EGFR + NSCLC based on the ADAURA trial, routine molecular profiling of early-stage lung cancer had not been standard of care. We hypothesize that there is a significant proportion of patients with resected adenocarcinoma with unknown EGFR status who could benefit from treatment that are missed with our current testing practices. Methods: We performed a retrospective analysis of Stage IB-IIIA lung adenocarcinomas resected at the University of Miami from 2014 to 2019. Eligible patients were identified from the Cancer Registry and information on EGFR mutation testing and treatment was obtained from chart review. We evaluated the prevalence of EGFR mutation testing in this population and outcomes based on EGFR mutation status. Disease free survival (DFS) and clinico-pathologic characteristics were evaluated. We estimated the number of patients that would have been eligible for EGFR testing and adjuvant osimertinib therapy in the pre-ADAURA era in our patient cohort. Results: A total of 120 patients had resected stage IB-IIIA adenocarcinoma during this five-year period (Stage IB 42.5%; Stage IIA 13.3%; Stage IIB 25%; Stage IIIA 19.2%) with a median age of 66 years. Most were females (59%), NHWs (51.5%), Hispanics (46.9%), and former smokers (66.7%). Out of patients with Stage IB-IIIA NSCLC with adenocarcinoma, 42.5% completed recommended adjuvant platinum-based chemotherapy. Only 40% of patients were referred for EGFR testing during this study period. The prevalence of EGFR mutations in this population was 10.8% (13 /120), but 59% of cases had no available EGFR testing. The most prevalent mutation was L858R (53.8%) followed by exon-19 deletions (30.8%). A total of 6 patients received an EGFR TKI therapy during the follow up period (2 in the adjuvant setting). With a median follow up of 12 mos, the rate of recurrence by stage was: Stage IB (3.9%); Stage IIB (10%); Stage IIIA (13%). Median time to disease progression or death was 13 months in this subgroup. There was no difference in disease free survival for patients with EGFR testing and those without results available in this short follow up period. Conclusions: Based on this retrospective review, up to 60% of patients with early-stage NSCLC with non-squamous histology have no available EGFR testing in the pre-ADAURA era. Of the anticipated 20% of patients with expected EGFR mutations based on historical controls, we have only identified half of patients that would have been eligible for adjuvant osimertinib. This study establishes the importance of upfront EGFR mutation testing in all NSCLC patients, not only to prognosticate, but also to identify the subset of patients who could benefit from adjuvant EGFR therapy.

67P Clinical outcomes of resected EGFR positive stage I-III NSCLC patients in the Midlands, UK

67P Clinical outcomes of resected EGFR positive stage I-III NSCLC patients in the Midlands, UK

OA06.04 Postoperative Chemotherapy Use and Outcomes from ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR Mutated NSCLC

OA06.04 Postoperative Chemotherapy Use and Outcomes from ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR Mutated NSCLC

OA06.03 Patient-Reported Outcomes from ADAURA: Osimertinib as Adjuvant Therapy in Patients with Resected EGFR Mutated (EGFRm) NSCLC

OA06.03 Patient-Reported Outcomes from ADAURA: Osimertinib as Adjuvant Therapy in Patients with Resected EGFR Mutated (EGFRm) NSCLC

LBA1 Osimertinib adjuvant therapy in patients (pts) with resected EGFR mutated (EGFRm) NSCLC (ADAURA): Central nervous system (CNS) disease recurrence

LBA1 Osimertinib adjuvant therapy in patients (pts) with resected EGFR mutated (EGFRm) NSCLC (ADAURA): Central nervous system (CNS) disease recurrence

Src-Homology 2 Domain-Containing Phosphatase 2 in Resected EGFR Mutation-Positive Lung Adenocarcinoma

IntroductionEGFR mutation-positive lung adenocarcinoma (LUAD) displays impaired phosphorylation of ERK and Src-homology 2 domain-containing phosphatase 2 (SHP2) in comparison with EGFR wild-type LUADs. We hypothesize that SHP2 expression could be predictive in patients positive with resected EGFR mutation versus patients with EGFR wild-type LUAD. MethodsWe examined resected LUAD cases from Japan and Spain. mRNA expression levels of AXL, MET, CDCP1, STAT3, YAP1, and SHP2 were analyzed by quantitative reverse transcriptase polymerase chain reaction. The activity of SHP2 inhibitors plus erlotinib were tested in EGFR-mutant cell lines and analyzed by cell viability assay, Western blot, and immunofluorescence. ResultsA total of 50 of 100 EGFR mutation-positive LUADs relapsed, among them, patients with higher SHP2 mRNA expression revealed shorter progression-free survival, in comparison with those having low SHP2 mRNA (hazard ratio: 1.83; 95% confidence interval: 1.05–3.23; p = 0.0329). However, SHP2 was not associated with prognosis in the remaining 167 patients with wild-type EGFR. In EGFR-mutant cell lines, the combination of SHP099 or RMC-4550 (SHP2 inhibitors) with erlotinib revealed synergism via abrogation of phosphorylated AKT (S473) and ERK1/2 (T202/Y204). Although erlotinib translocates phosphorylated SHP2 (Y542) into the nucleus, either RMC-4550 alone, or in combination with erlotinib, relocates SHP2 into the cytoplasm membrane, limiting AKT and ERK1/2 activation. ConclusionsElevated SHP2 mRNA levels are associated with recurrence in resected EGFR mutation-positive LUADs, but not in EGFR wild-type. EGFR tyrosine kinase inhibitors can enhance SHP2 activation, hindering adjuvant therapy. SHP2 inhibitors could improve the benefit of adjuvant therapy in EGFR mutation-positive LUADs.