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F. Shepherd



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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
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      MINI05.13 - Treatment of EGFR/ALK-Driven Non-Small Cell Lung Cancer (NSCLC) Brain Metastases: Impact of First-Line Whole Brain Radiotherapy on Outcome (ID 1251)

      F. Shepherd

      • Abstract
      • Presentation
      • Slides

      Background:
      Brain metastases (mets) in EGFR/ALK-driven NSCLC are common, and frequently pose treatment dilemmas. Effective systemic therapy with tyrosine kinase inhibitors (TKIs) controls extracranial disease in up to 70% of patients, but often radiotherapy is required for intracranial control. As whole brain radiation (WBRT) may be associated with neurocognitive toxicity, we aimed to evaluate the impact of molecularly targeted therapy and stereotactic radiotherapy (SRS) for EGFR/ALK-driven NSCLC on intracranial disease control with and without WBRT.

      Methods:
      This retrospective analysis included patients treated with EGFR/ALK-positive NSCLC at Princess Margaret Cancer Centre from 1998-2015, with brain mets at lung cancer diagnosis or during treatment/follow-up. Demographic data were collected from electronic patient records. Time to intracranial progression (TTIP) and overall survival (OS) were calculated from date of diagnosis of brain mets, using the cumulative incidence function and Kaplan-Meier methods respectively; differences between groups were tested with Gray’s or log-rank test.

      Results:
      From 1998-2015, 162 patients with brain mets from EGFR/ALK-driven NSCLC were identified: 138 in the EGFR cohort, 23 in the ALK cohort and one included in both cohorts for analysis, whose tumour carries both an EGFR mutation and ALK rearrangement. Table 1 contains clinical characteristics and treatment details. In the EGFR cohort, initial brain mets treatment consisted of systemic therapy alone in 19 patients (17 TKI, 2 chemotherapy), SRS +/- surgery in 27 patients and WBRT +/- SRS/surgery in 88 patients. 1-year intracranial progression rates were 26%, 32% and 12%, respectively, and median TTIP was 18, 16 and 40 months [p=0.12]. Median OS was 26, 27 and 34 months respectively [p=0.49]. In the ALK cohort, initial brain mets treatment consisted of systemic therapy alone in 4 patients (1 TKI, 3 chemotherapy), SRS/surgery alone for 4 patients and WBRT +/- SRS/surgery for 15 patients. 1-year intracranial progression rates were 50%, 50% and 13%, respectively, and median TTIP was 18, 14 and 69 months [p=0.028]. Median OS was 35 months, not reached and 51 months, respectively [p=0.75]. Multivariable analysis for the whole group showed that age [p=0.021], number of brain mets [p=0.012] and extracranial control [p=0.008] were significantly associated with OS, but not WBRT [p=0.61].

      Conclusion:
      In this cohort of patients with brain mets from EGFR/ALK-driven NSCLC, patients treated with WBRT trended to longer TTIP. Although not statistically significant, our data also show a trend towards longer survival in patients who received WBRT. These observations require further validation in this patient population.

      EGFR (N=139) ALK (N=24)
      Median Age (Range) 59(29-86) 53(31-77)
      Female Sex 93(67%) 15(62%)
      Ethnicity Asian Caucasian Other 58(42%) 63(45%) 18(13%) 7(29%) 13(54%) 4(17%)
      Smoking Never Smoker Former/Current Smoker Unknown 108(77%) 30(22%) 1(1%) 19(79%) 5(21%) 0
      ECOG PS (Diagnosis) 0 1 2-4 66(48%) 67(48%) 6(4%) 7(29%) 14(58%) 3(13%)
      Brain Mets at Stage IV diagnosis 93(67%) 13(52%)
      Number of Brain Mets 1 2-4 5+ N/A 32(23%) 39(28%) 62(45%) 6(4%) 9(38%) 6(24%) 9(38%) 0
      Symptomatic Brain Mets No Yes 78(56%) 61(44%) 16(67%) 8(33%)
      Initial Brain Mets treatment WBRT WBRT+SRS/Surgery SRS+/-Surgery Systemic Therapy None 71(51%) 17(12%) 27(19%) 19(14%) 5(4%) 13(54%) 3(12%) 4(17%) 4(17%) 0


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    MINI 14 - Pre-Clinical Therapy (ID 119)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI14.12 - Genomic Profiling of Patient-Derived Xenografts Identify Passenger Aberrations Associated with Better Prognosis in Non-Small Cell Lung Cancer (ID 1735)

      F. Shepherd

      • Abstract
      • Slides

      Background:
      Patient-derived tumor xenografts (PDXs) increasingly are being used as preclinical models to study human cancers, test novel therapeutics, and identify potential biomarkers, as they more accurately model human cancers than established tumor cell line cultures. However, uncertainty remains as to how well the genomic characteristics of patient non-small cell lung cancer (NSCLC) are recapitulated in these PDX models.

      Methods:
      PDXs were established by implantation of surgically resected NSCLC patient tumors into the subcutaneous or sub-renal capsule of non-obese diabetic severe combined immune deficient (NOD-SCID mice. Comprehensive genomic profiling including exome, gene copy number, DNA methylation and mRNA expression were conducted on 36 independent PDX models, their matched patient tumors and normal lung tissue. Publicly available cell line and TCGA data were used for comparison. Integrative analysis was performed to identify genomic alterations in PDXs that are associated with significant clinical outcomes in patients.

      Results:
      From 441 resected NSCLC tumors, 127 serially transplantable and stable PDX models were established. Among 264 NSCLC patients with at least 3-years follow-up, patients whose tumor formed stable PDXs (versus those who did not) showed significantly worse disease free (HR=3.12, 95% CI =2.02-4.83, P<0.0001) and overall survival (HR=4.08, 95% CI =2.16-7.73, P<0.0001), after multivariable adjustment for clinical pathological factors. Genomic and transcriptomic profiling of 36 PDXs showed greater similarity in somatic alterations between PDX and primary tumors than with published cell line data. In addition to known mutations, we found at least 16 non-synonymous somatic mutations in known oncogenes and tumor suppressors that have never been reported. All these mutations had higher observed variant allele frequency in PDXs compared to their matched patient tumors, suggesting that these were tumor sub-clones selected or enriched for growth in the PDXs. Tumor models characterized by a higher number of somatic alterations among 865 frequently altered genes were associated with better overall patient survival (HR=0.15, p=0.00015) compared to patients with corresponding PDXs characterized by higher alteration number; this was validated in the TCGA lung cancer dataset patients (HR=0.28, p=0.000022). These 865 genes were enriched for those encoding for proteins involved in cell adhesion and interactions with the extracellular matrix, and a quarter of the genomic alterations would putatively form neo-antigens implicating a potential role of immune response in the observed improved patient survival.

      Conclusion:
      PDXs are close preclinical models of patient tumors. Further investigations of passenger mutations may clarify their clinical impact on interactions between tumor cells, stroma, immune microenvironment and patient prognosis.

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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: 1
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      MINI16.08 - AZD9291 in Pre-Treated T790M Positive Advanced NSCLC: AURA2 Phase II Study (ID 1406)

      F. Shepherd

      • Abstract
      • Presentation
      • Slides

      Background:
      The epidermal growth factor receptor (EGFR) T790M mutation is found in about half of patients who have developed resistance to EGFR-tyrosine kinase inhibitors (TKIs), gefitinib or erlotinib. AZD9291 is an oral, potent, irreversible EGFR-TKI selective for both EGFR-sensitizing (EGFRm) and T790M resistance mutations. In the Phase I AURA study, AZD9291 80 mg (dose selected for further evaluation) was found to be clinically active, with an acceptable tolerability profile. This ongoing AURA2 Phase II study (NCT02094261) investigates the efficacy and safety of AZD9291 80 mg once daily after previous EGFR-TKI treatment in patients with EGFRm and T790M positive advanced NSCLC.

      Methods:
      AURA2 (NCT02094261) is a global, open-label, single-arm Phase II study. To be eligible, all patients had a mandatory tumor sample taken after disease progression on the most recent line of therapy, for confirmation of T790M positive status by central laboratory testing using the cobas™ EGFR Mutation Test. Further inclusion criteria included measurable disease, World Health Organization performance status (WHO PS) 0 or 1, and acceptable organ function; stable brain metastases were allowed. Patients receive AZD9291 at 80 mg once daily 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), and safety. Planned enrollment was 175 patients to give an ORR with 95% confidence interval (CI) within ±8%. The data cut-off was January 9, 2015.

      Results:
      Recruitment is complete and 210 patients were enrolled; 12 patients did not have measurable disease at baseline by ICR and are excluded from the evaluable-for-response set. By central testing, in addition to T790M, patients had background EGFR mutation: Ex19del, 65%; L858R, 32%; other, 3%. Baseline characteristics: median age, 64 years; female, 70%; WHO PS 0/1, 40%/60%; Asian, 63%; second-/≥third-line, 32%/68%. Median treatment exposure was 4.0 months and 183 patients remain on treatment at the data cut-off. ORR by ICR was 64% (127/198; 95% CI 57, 71) and DCR was 90% (95% CI 85, 94). Investigator-assessed ORR was 64% (135/210; 95% CI 57, 71). Median DoR and median PFS have not been reached (maturity 6% and 20%, respectively). The estimated proportion of patients who are alive and progression free is 82% and 70% at 3 and 6 months, respectively. The most common all-causality adverse events (AEs) were diarrhea, 34% (1% Gr≥3) and grouped rash terms 40% (0.5% Gr≥3); 38 (18%) patients experienced Gr≥3 AEs. Interstitial lung disease grouped terms were reported in four (1.9%) 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:
      AZD9291 80 mg once daily demonstrates clinical activity and manageable tolerability in patients with EGFRm, T790M mutation positive advanced NSCLC that has progressed on or after EGFR‑TKI treatment. AZD9291 is being investigated in the randomized AURA3 Phase III study (NCT02151981) in comparison with platinum-based doublet chemotherapy.

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    MINI 29 - Meta Analyses and Trial Conduct (ID 156)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI29.12 - Patients with Advanced Non-Small Cell Lung Cancer: Are Research Biopsies a Barrier to Participation in Clinical Trials? (ID 663)

      F. Shepherd

      • Abstract
      • Presentation
      • Slides

      Background:
      The evolution of targeted therapy in non-small cell lung cancer (NSCLC) has led to growing complexity of clinical research and a heightened expectation of clinical benefit for participants. Clinical trials in NSCLC increasingly require mandatory tumour samples or research biopsies, both potential barriers for trial participation. We assessed the impact of performing research biopsies in advanced NSCLC on clinical trial enrollment.

      Methods:
      We conducted a retrospective chart review of patients with advanced NSCLC evaluated for systemic therapy clinical trials at the Princess Margaret Cancer Center from January 2007 to March 2015.

      Results:
      Of 55 clinical trials reviewed, 38 required tumor samples for enrolment. Six mandated fresh tumor biopsies, whereas archival samples were permitted for 32 trials. All studies were linked to investigational therapy except one trial of molecular profiling not linked to an investigational treatment. Confirmation of a pre-specified biomarker was required in 23 trials in order to receive investigational treatment. Trial participation was offered to 640 patients at 940 unique study encounters, with some patients enrolling in multiple trials. Of 549 encounters where study treatment was offered, 60% proceeded to receive study treatment. Those considering trials without mandatory tissue requirements were more likely to proceed to study enrolment than those considering trials with these requirements (83% vs. 55%, p<0.0001). Those considering trials permitting use of archival tissue were more likely to begin study treatment than those considering trials mandating fresh research biopsies (59% vs. 38%, p=0.0007). For trials requiring current tumour samples, 127 research biopsies were performed. Participants proceeded to study treatment in 51% of these encounters. Study treatment was not offered for the remaining encounters due to lack of the pre-specified biomarker (28%), insufficient biopsy tissue (6%) or non-biopsy related exclusion criteria (15%). Among all 549 trial encounters, the most common barriers to trial enrollment included lack of the pre-specified biomarker (35%), withdrawal of consent (20%), other study exclusion criteria (16%), insufficient biopsy tissue (10%), deteriorating clinical status (10%) and death (5%). Of 391 encounters for the molecular profiling trial, 72% successfully completed molecular profiling. Twenty-two percent had insufficient tissue for analysis and 3% died prior to completion of molecular profiling.

      Conclusion:
      With the evolution of personalized medicine, a growing number of NSCLC trials require tumour tissue for treatment eligibility. This has emerged as a significant barrier to clinical trial enrollment. Potential solutions include routine tissue banking at diagnosis, facilitating use of available diagnostic samples (e.g. fine needle aspirates) for trials, development of circulating DNA assays for trials, and more resources for timely tissue acquisition.

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    ORAL 06 - Next Generation Sequencing and Testing Implications (ID 90)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      ORAL06.03 - Genome-Wide Gene Copy Number Analysis by OncoScan<sup>TM</sup> FFPE Assay in 976 Resected NSCLC From LACE-Bio2 (ID 1561)

      F. Shepherd

      • Abstract
      • Presentation
      • Slides

      Background:
      Genome wide SNP array studies have identified systematic gene copy number aberrations (CNA) in non-small cell lung cancer (NSCLC), but their prognostic implication is unknown. This study aimed to investigate associations between CNAs and survival using the LACE-Bio bio-bank. The LACE-Bio consortium includes large clinical trials comparing adjuvant platinum-based chemotherapy to observation after complete resection of stage I-III NSCLC.

      Methods:
      DNA was extracted from FFPE tumor samples from 3 pivotal adjuvant chemotherapy trials (CALGB 9633, IALT, JBR.10); 1013 samples were profiled using Affymetrix OncoScan[TM] arrays with over 300,000 probes and normalized relative to a pool of normal tissues. Segmentation was performed using the CBS algorithm and minimally recurrent regions (MCR) across the series identified by CGHregions. All analyses were performed on the level of MCRs. CNAs were correlated with clinicopathological factors and adjusted for the False Discovery Rate (FDR). The primary endpoint, disease-free survival (DFS), was assessed via univariate Cox models stratified by trial and adjusted for treatment, age, sex, PS, histology, T, and N stage.

      Results:
      Among 976 successfully profiled samples, 414 (42%) were adenocarcinoma (ADC), 430 (44%) squamous cell carcinoma (SCC) and 132 (14%) other NSCLC; 710 (73%) were male. Across the 431 MCRs identified, patients had on average 94 (SD 69) CNAs: 51 gains and 43 losses. A gain or loss was observed in at least 10% of patients for 177 and 166 regions respectively. The most common gains (up to 48%) were on chromosomes 1p, 3q, 5p, 6p, and 22q. The most common losses (up to 40%) were on chromosomes 3p, 8p and 9p. The size of 253 of the 431 MCRs (59%) was smaller or equal to 3Mb (and 79% ≤10 Mb). Sensitivity analyses on the subset of samples with optimal quality (n=777, defined by MAPD<0.3) gave consistent results. The CNA frequency of 195 regions was significantly different with FDR≤0.05 between ADC and SCC (of which 49% regions of size ≤3Mb and 71% ≤10Mb); the most significant were more gains in 3q, 22q and 12 in SCC and more losses in 3p, 4, 5q in SCC. With a median follow-up of 5.3 years, 510 DFS events and 451 deaths were recorded. In univariate analyses for DFS, 13 regions in loci 19p11–13, 7p12, 9p21, 15q14 had a raw p-value <0.005 (FDR<0.13, the top 8 corresponded to FDR≤0.05); 9 of those 13 regions were of size ≤3Mb (12 regions ≤10Mb). In adjusted analyses, 10 of the 13 regions retained raw adjusted p-values ≤0.005 (FDR≤0.15). Losses of focal regions including CDKN2A/B and STK11 (≤3Mb) were associated with poorer DFS: the hazard ratio (HR) for a 2-fold copy number decrease in region 9p21.3 (including CDKN2A/B) was 1.50 (95% CI: 1.2–1.9, P<0.001, FDR=0.02), and the HR for a 2-fold copy number decrease in 19p13 (including STK11) was 2.4 (1.3–4.3, P=0.005, FDR=0.15). Similar results were obtained for overall survival and lung-cancer specific survival. Results of histology-specific analyses will be presented.

      Conclusion:
      These large-scale genome-wide analyses of gene CNA provide new candidate prognostic markers for stage I-III NSCLC.

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    ORAL 21 - Biology - Moving Beyond the Oncogene to Oncogene-Modifying Genes (ID 118)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      ORAL21.05 - p53/KRAS Mutation Status Does Not Predict Sensitivity to Chemotherapy in NSCLC PDXs (ID 2459)

      F. Shepherd

      • Abstract
      • Presentation
      • Slides

      Background:
      The LACE-Bio group assessed the prognostic and predictive values of KRAS and p53 mutations in 1543 completely resected non-small cell lung cancer (NSCLC) tumors. The predictive value of combined KRAS/p53 mutations for survival benefit from adjuvant chemotherapy was evaluated on 49 patients and chemotherapy was deleterious in this group compared to observation (HR 2.49 CI 95% [1.10 – 5.66], p=0.03). Patients with tumors harboring combined KRAS/p53 mutations had a worse outcome when treated with adjuvant chemotherapy compared patient with double wild type (WT) tumors (HR 3.03 (95% CI [1.29 – 7.15], p=0.01, interaction p=0.06). We have compared the chemo-sensitivity of patient derived xenografts (PDXs) with double p53/KRAS mutations, single p53, single KRAS mutation or double WT. 0

      Methods:
      Surgically resected early stage lung adenocarcinomas (ADC) were implanted into non-obese diabetic severe combined immune deficient (NOD-SCID) mice. Fourteen lung ADC PDXs with various p53/KRAS status were revived and implanted: 11 engrafted and were expanded for comparison of treatment vs control. For each model, 6 replicates were included in treatment and control arms. Chemotherapy (cisplatin 3 mg/kg and vinorelbine 7 mg/kg intraperitoneally weekly) was initiated in the PDXs at tumor volumes of 150 mm[3].

      Results:
      Four models were p53/KRAS double mutant, 4 p53 mutant, 2 KRAS mutant and 1 double WT. The 4 double mutant PDXs responded to chemotherapy, 2 with reduced (SD) and 2 inhibited (PR) growth. Among the 4 PDXs with p53 mutation only, 2 responded (1 PR and 1 SD) and 2 were resistant. Among the 2 PDXs with KRAS mutation only, 1 had a complete response, but relapsed at treatment arrest and 1 achieved PR. The double WT PDX was highly sensitive to chemotherapy (PR) but also relapsed at treatment arrest.

      Conclusion:
      Among these 11 PDXs, the p53/KRAS mutation status did not predict chemo-sensitivity to cisplatin/vinorelbine, one of the most active adjuvant chemotherapy regimens in NSCLC. As these PDXs were molecularly profiled, we currently are investigating other biomarkers that might predict their sensitivity or resistance to chemotherapy.

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    P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P2.04-026 - Second Generation EGFR TKIs Inhibit Tumor Growth in a Chemo-Resistant Squamous Cell Lung Cancer Patient Derived Xenograft Model (ID 1265)

      F. Shepherd

      • Abstract
      • Slides

      Background:
      In clinical trials testing the efficacy of first generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), occasional responses were observed in patients with lung squamous cell carcinomas (LSCC) (Shepherd FA, et al. New Engl J Med 2005) and survival benefit was confirmed for erlotinib in a subset analysis of male, ever-smokers with LSCC (Clark GM, et al. Clin Lung Cancer 2006). Currently, the LUX-Lung 8 phase III clinical trial is comparing afatinib versus erlotinib in the second-line setting for LSCC after cisplatin-based chemotherapy (Goss GD, et al. ESMO 2014). Preclinical data indicate that high EGFR protein expression may be predictive of response to erlotinib in EGFR wild type LSCC (Cranston et al, AACR 2013). Herein we assessed and compared the anti-tumor efficacy of different EGFR inhibitors in chemo-resistant squamous cell lung cancer patient derived xenograft (PDX) models with high EGFR expression and EGFR amplification.

      Methods:
      The cryopreserved PDX model established from a resected early stage LSCC was revived in non-obese diabetic severe combined immunodeficient mice (NOD SCID), expanded and subsequently treated with chemotherapy (cisplatin 3 mg/kg and vinorelbine 7 mg/kg intraperitoneally [IP]), cetuximab 20 mg/kg IP, and daily oral schedules were followed for erlotinib 50 mg/kg, afatinib 20 mg/kg, dacomitinib 3 mg/kg. For each model, 6 mice were used in each of the different treatment and the control arms. Treatment was initiated in the PDXs at a tumor average volume of 150 mm[3].

      Results:
      The PDX was derived from a 57 year old male, smoker, following right pneumonectomy for a stage IIIB (T4N1M0) LSCC. This patient received adjuvant cisplatin/vinorelbine, but relapsed three weeks after the end of cycle 4 and died a week later. The tumor had a high EGFR expression by immunohistochemistry (H score = 300) and EGFR amplification (clusters) by fluorescent in situ hybridization. The PDX was EGFR wild type by Illumina exome sequencing and OncoCarta[TM ]MassArray mutation screen (Sequenom), also was refractory to cisplatin/vinorelbine. Reduced growth rate (stable disease, SD) was obtained with erlotinib and cetuximab. Treatment with afatinib and dacomitinib resulted in tumor growth inhibition (partial response, PR). The PDX developed resistance to dacomitinib after 100 days of treatment, but continued to be inhibited by afatinib after 215 days of treatment.

      Conclusion:
      This study shows the efficacy of second generation especially afatinib irreversible EGFR TKIs in a chemoresistant LSCC PDX, with high wild type EGFR expression and EGFR amplification. Our results lend further support to the LUX-Lung 8 trial, and also the use of PDX to model therapeutic responses in lung cancer.

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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P3.04-044 - EGFR and ALK Status Influence Health Utility and Global Quality of Life Scores in Patients with Metastatic Lung Cancer (ID 1613)

      F. Shepherd

      • Abstract
      • Slides

      Background:
      EGFR mutations and EML4-ALK rearrangements play important roles in prognosis and response to treatment. While extending survival is a main goal of treatment, improving symptoms, well-being, and quality of life is an equally important priority.

      Methods:
      At Princess Margaret Cancer Centre, a cross-sectional study evaluated 224 outpatients with metastatic lung cancer who completed demographic and EQ5D-3L questionnaires generating health utility scores (HUS, 0-1) and a visual analogue scale (VAS) slider (0-100). Patients rated their ECOG performance status (0-4), and described their health over the last month from 1 (excellent) to 5 (poor). Results were correlated with clinical and demographic data. Our objective was to compare HUS and global quality of life by mutational status. Patients with EGFR mutations and ALK rearrangements were enriched through targeted enrolment, while patients with neither alteration were selected randomly from the same outpatient clinics.

      Results:
      94 patients (42%) had an EGFR mutation, 23 (10%) an ALK rearrangement and 107 (48%) had neither (“wildtype”) in their tumor. Participation rate was 87%. Characteristics of the populations were as expected, with higher rates of never smokers in patients with EGFR or ALK alterations (p<0.0001), greater proportion of Asians (p=0.0004), and higher proportion of adenocarcinoma (p<0.0001). Current systemic treatment differed among groups, as the majority of patients with driver mutations were receiving targeted agents at the time of assessment (77% EGFR and 65% ALK vs 7% wildtype). Conversely, wildtype patients were more likely on chemotherapy (6% vs 17% vs 38%) or not on treatment (17% vs 17% vs 47%, p<0.0001). Patients filled questionnaires on average 25 months after initial diagnosis of lung cancer. Patients with EGFR mutations (97%) or ALK rearrangements (100%) were more often ECOG performance status 0-1 at the time of diagnosis of stage IV disease than wildtype individuals (86%, p=0.02). For quality of life analysis, we regrouped the patients with EGFR/ALK alterations (n=117). Their mean HUS was better than for wildtype patients (0.80 vs 0.71, p=0.0003), their mean VAS slider was higher (66.9 vs 60.8, p=0.0381) and their mean self-rated ECOG scores was better (0.90 vs 1.26, p=0.022).

      Conclusion:
      In a clinical population, patients with metastatic lung cancer harboring EGFR and ALK alterations report superior HUS and global quality of life scores when compared with patients without these molecular changes, during the course of their therapy. This is reflected in higher proportion of patients on active therapy, particularly with molecularly targeted agents, and with improved self-reported performance scores. Health utility values used in economic analyses of metastatic lung cancer patients in clinical practice should be specific for different mutations.

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    YIS - Young Investigator Session incl. Q & A with Longstanding IASLC Members (ID 238)

    • Event: WCLC 2015
    • Type: Young Investigator Session
    • Track: Other
    • Presentations: 1
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      YIS.07 - Q & A with Longstanding IASLC Members (ID 3517)

      F. Shepherd

      • Abstract
      • Slides

      Abstract not provided

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