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H. Borghaei



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    ISS03 - Industry Supported Symposium: Non-Small Cell Lung Cancer: The Programmed Death-Ligand 1 (PD-L1) Receptor as a Target for Monotherapy and in Combination – Merck-Pfizer Alliance (ID 437)

    • Event: WCLC 2016
    • Type: Industry Supported Symposium
    • Track:
    • Presentations: 1
    • Moderators:S. Popat
    • Coordinates: 12/04/2016, 03:30 PM - 05:00 PM, Hall C2
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      ISS03.05 - Anti-PD-L1 Agents: Opportunities for Differentiation (ID 7041)

      H. Borghaei

      • Abstract
      • Slides

      Abstract not provided

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    MA07 - ALK-ROS1 in Advanced NSCLC (ID 385)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      MA07.02 - Updated Efficacy and Safety Data from the Phase 2 NP28761 Study of Alectinib in ALK-Positive Non-Small-Cell Lung Cancer (Now Available) (ID 4918)

      H. Borghaei

      • Abstract
      • Presentation
      • Slides

      Background:
      Alectinib, a CNS-active and highly selective ALK inhibitor, has efficacy in patients with ALK-positive NSCLC with and without previous crizotinib treatment. Updated efficacy and safety from the alectinib phase 2 North American NP28761 study (NCT01871805) of patients with ALK-positive NSCLC previously treated with crizotinib, with 15 months’ additional follow-up from the primary analysis and 9 months’ additional follow-up from the previous analysis are presented.

      Methods:
      Patients ≥18 years old with ALK-positive NSCLC (FDA-approved FISH test), disease progression following crizotinib, and ECOG PS ≤2 were enrolled. Patients received oral alectinib (600mg) twice daily until progression, death or withdrawal. Primary endpoint: overall response rate (ORR) by independent review committee (IRC; RECIST v1.1.) Secondary endpoints: investigator-assessed ORR; progression-free survival (PFS); overall survival (OS), CNS ORR (CORR); disease control rate (DCR); safety.

      Results:
      At the updated cut-off (22 January 2016) an additional 15 months' follow-up from the primary analysis, 87 patients were enrolled. Median follow-up: 17.0 months (range 1.1–28.6). ORR in the response evaluable population (REP; n=67) by IRC: 52.2% (95% CI 39.7–64.6), median duration of response: 14.9 months. Median PFS and OS: 8.0 and 22.7 months, respectively. Table 1 presents other efficacy endpoints. Grade ≥3 AEs were reported in 41% of the safety population (n=87); most common: elevated levels of blood creatine phosphokinase (8%), alanine aminotransferase (6%), aspartate aminotransferase (5%). Two patients withdrew due to AEs; 28% had AEs leading to dose modification/interruption. Mean dose intensity was 92.0%.

      IRC REP Responders, n CR, n (%) PR, n (%) SD, n (%) PD, n (%) Missing/NE, n (%) DCR, % (95% CI) n=67[*] 35 0 (0) 35 (52.2) 18 (26.9) 11 (16.4) 3 (4.5) 79.1 (67.4,88.1)
      Investigator REP Responders, n ORR, % (95% CI) n=87 [46[†]] 52.9 (41.9, 63.7)
      Measurable baseline CNS lesions (IRC)‖ Responders, n CORR, % (95% CI) Measurable/non-measurable baseline CNS lesions (IRC) Responders CORR,[‖] % (95% CI) n=16 12[‡] 75.0 (47.6, 92.7) n=52 21[§] 40.4 (27.0, 54.9)
      *n=20 did not have measurable disease per IRC and were not included in the IRC REP; [†]2 CR;[ ‡]4 CR;[ §]13 CR; [‖]non-measurable disease classified as CR, non-CR/non-PD or PD; NE=not evaluable/estimable

      Conclusion:
      Alectinib demonstrated durable responses, encouraging OS findings, good tolerability and an acceptable safety profile consistent with previous reports in this update of the NP28761 study with extended follow-up.

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    MA09 - Immunotherapy Combinations (ID 390)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 1
    • Now Available
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      MA09.02 - Pembrolizumab + Carboplatin and Pemetrexed as 1st-Line Therapy for Advanced Non–Small Cell Lung Cancer: KEYNOTE-021 Cohort G (Now Available) (ID 5787)

      H. Borghaei

      • Abstract
      • Presentation
      • Slides

      Background:
      Platinum doublet chemotherapy ± bevacizumab is standard first-line therapy for patients with advanced non–small cell lung cancer (NSCLC) without genetic aberrations. Single-agent pembrolizumab exhibits robust antitumor activity in PD-L1–positive advanced NSCLC. Cohort G of the multicenter, open-label, phase 1/2 multicohort KEYNOTE-021 study (ClinicalTrials.gov, NCT02039674) evaluated the efficacy and safety of pembrolizumab + carboplatin and pemetrexed compared with carboplatin and pemetrexed in patients with treatment-naive advanced nonsquamous NSCLC with any PD-L1 expression.

      Methods:
      Cohort G enrollment criteria included patients with stage IIIB/IV nonsquamous NSCLC, no activating EGFR mutation or ALK translocation, no prior systemic therapy, measurable disease, ECOG performance status 0-1, and adequate tumor sample for assessment of PD-L1 status, regardless of PD-L1 expression. Patients were randomized 1:1 to 4 cycles of pembrolizumab 200 mg Q3W + carboplatin AUC 5 (5 mg/mL/min) + pemetrexed 500 mg/m[2] Q3W or carboplatin AUC 5 (5 mg/mL/min) + pemetrexed 500 mg/m[2] Q3W alone, followed by maintenance pemetrexed ± pembrolizumab. Pembrolizumab was given for ≤35 cycles. Randomization was stratified by PD-L1 expression (positive [tumor proportion score, or TPS, ≥1%] vs negative [TPS <1%]). Crossover to pembrolizumab monotherapy was allowed for eligible patients who experienced disease progression (RECIST v1.1) on chemotherapy. Response was assessed by central imaging vendor review every 6 weeks for first 18 weeks, every 9 weeks through year 1, and every 12 weeks in year 2. The primary end point was objective response rate (ORR); secondary end points included progression-free survival (PFS), duration of response, and overall survival (OS). Comparison between arms was assessed using the stratified Miettinen and Nurminen method (ORR) and stratified log-rank test (PFS, OS).

      Results:
      As of January 2016, 123 patients (60 in the pembrolizumab + chemotherapy arm, 63 in the chemotherapy arm) had been enrolled in cohort G. Data on ORR, duration of response, safety, and preliminary PFS and OS results will be available by August 2016.

      Conclusion:
      The conclusion will be updated at the late-breaking submission stage.

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    MA16 - Novel Strategies in Targeted Therapy (ID 407)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 1
    • Now Available
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      MA16.10 - Lung-MAP (S1400) Lung Master Protocol: Accrual and Genomic Screening Updates (Now Available) (ID 3995)

      H. Borghaei

      • Abstract
      • Presentation
      • Slides

      Background:
      Lung-MAP (S1400), is a master protocol that incorporates genomic testing of tumors through a next generation sequencing (NGS) platform (Foundation Medicine) and biomarker-driven (matched) therapies for patients with squamous cell lung cancer (SCCA) after progression on first-line chemotherapy.

      Methods:
      The Lung-MAP trial, activated June 16, 2014, includes 3 matched- and 1 non-match study. Matched studies include: S1400B evaluating taselisib, a PI3K inhibitor, S1400C evaluating palbociclib, a CDK 4/6 inhibitor and, S1400D evaluating AZD4547, an FGFR inhibitor. The non-match study S1400I tests nivolumab + ipilimumab vs. nivolumab. Two studies have closed: S1400E evaluating rilotumumab an HGF monoclonal antibody + erlotinib closed 11/26/2014 and S1400A evaluating MEDI4736 in non-match pts, closed 12/18/2015.

      Results:
      From June 16, 2014 to June 15, 2016, 812 pts were screened and 292 pts registered to a study: 116 to S1400A, 27 to S1400B, 53 to S1400C, 32 to S1400D, 9 to S1400E and 55 to S1400I. Demographics: Screening was successful for 705 (87%) of screened eligible pts. Median age 67 (range 35-92); male 68%; ECOG PS 0-1 88%, PS 2 10%; Caucasian 85%, Black 9%, other 5%; never/former/current smokers 4%/58%/36%. Table 1 displays biomarker prevalence; 39% of pts matched; 33.9%, 4.8%, and 0.3% with 1, 2, and all 3 biomarkers, respectively. Tumor mutation burden (TMB) was available for 636 (90.4%) of eligible pts. The distribution of TMB is: 126 (19.8%) low (≤5 mutations Mb), 415 (65.1%) intermediate (6-19 mutations/Mb), and 96 (15.1%) high (≥20 mutations/Mb). The median TMB was 10.1.

      Conclusion:
      Genomic screening is feasible as part of this master protocol designed to expedite drug registration, confirm anticipated prevalence of targeted alterations in SCCA and reveal intermediate or high TMB in most (80.2%) pts. Treatment results are not yet available as patients continue to accrue. Clinical trial information: NCT02154490

      Total FGFR CDK PIK3CA
      FGFR (15.9%) 12.9% 2.4% 0.6%
      CDK (18.8%) 14.6% 1.8%
      PIK3CA (8.8%) 6.4%
      Biomarker prevalence and overlap.


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    OA03 - Immunotherapy Checkpoint Inhibitors in Advanced NSCLC (ID 367)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 2
    • Now Available
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      OA03.01 - First-Line Nivolumab Monotherapy and Nivolumab plus Ipilimumab in Patients with Advanced NSCLC: Long-Term Outcomes from CheckMate 012 (Abstract under Embargo until December 5, 7:00 CET) (Now Available) (ID 5364)

      H. Borghaei

      • Abstract
      • Presentation
      • Slides

      Background:
      Nivolumab, a programmed death 1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved efficacy and tolerability vs docetaxel in patients with advanced NSCLC that progressed on or after platinum-based chemotherapy and is approved in >50 countries in this patient population. We report efficacy and safety data from a phase 1 study (CheckMate 012; NCT01454102) evaluating first-line nivolumab in patients with advanced NSCLC.

      Methods:
      Patients (N=52) with advanced, chemotherapy-naive NSCLC (any histology) were treated with nivolumab monotherapy at 3 mg/kg IV Q2W until disease progression or unacceptable toxicity. Safety and tolerability was the primary study objective. Efficacy, as measured by objective response rate (ORR) and 24-week progression-free survival (PFS) rate per RECIST v1.1, was the secondary objective. Overall survival (OS) was an exploratory endpoint.

      Results:
      Treatment-related adverse events (TRAEs) were reported in 71% (any grade) and 19% (grade 3‒4) of patients. The most frequent select TRAEs (those with potential immunologic causes) by category were skin, endocrine, and gastrointestinal (Table). With a median follow-up of 14.3 months (range, 0.2 to 30.1), the confirmed ORR was 23% (12/52) and 8% (4/52) of patients had complete responses. Of the 12 responses, 8 (67%) were ongoing at the time of database lock; median duration of response was not reached. Median OS was 19.4 months (range, 0.2‒35.8+). The 24-week PFS rate was 41% (95% CI: 27‒54); 18-month OS rate was 57% (95% CI: 42‒70). Updated long-term data will be presented, including 2-year OS and will represent the longest follow-up to date for a PD-1/PD-L1 inhibitor for first-line advanced NSCLC. Updated data from patients treated with nivolumab plus ipilimumab (N = 77) will also be presented.

      Nivolumab monotherapy (N=52)
      Safety
      Any grade / grade 3‒4 TRAEs,[a] n (%) 37 (71) / 10 (19)
      Any grade / grade 3‒4 select TRAEs,[a,b] by category (≥10% of patients), n (%)
      Skin 13 (25) / 2 (4)
      Endocrine 7 (14) / 0 (0)
      Gastrointestinal 6 (12) / 1 (2)
      Any grade / grade 3‒4 TRAEs leading to discontinuation, n (%) 6 (12) / 6 (12)
      Efficacy
      Confirmed ORR,[c] n (%) [95% CI] 12 (23) [13‒37]
      CR 4 (8)
      PR 8 (15)
      SD 14 (27)
      PD 20 (38)
      Unable to determine[d] 6 (12)
      Median DOR, mo (range) NR (4.2‒25.8+)
      Ongoing responders, n/N (%) 8/12 (67)
      Median PFS, mo (range) 3.6 (<0.1+‒28.0+)
      24-week PFS, % (95% CI) 41 (27‒54)
      Median OS, mo (range) 19.4 (0.2‒35.8+)
      1-year OS, % (95% CI) 73 (59‒83)
      18-month OS, % (95% CI) 57 (42‒70)
      Efficacy and safety analyses, except for OS, were based on a March 2015 database lock; OS analyses were based on an August 2015 database lock.[a]No grade 5 events were reported.[b]AEs with a potential immunologic cause.[c]Includes patients with initial observations of CR and PR that were subsequently confirmed by repeat scans performed no earlier than 4 weeks after the original observation.[d]Includes patients who discontinued therapy because of disease progression before first assessment or patients only with assessments suggestive of, but that did not satisfy, the required minimum duration for SD. CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease; DOR = duration of response; NR = not reached.


      Conclusion:
      First-line nivolumab monotherapy in patients with advanced NSCLC had a similar safety profile as previously reported in second-line NSCLC and other tumors, was well tolerated, and demonstrated durable efficacy.

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      OA03.05 - Analysis of Early Survival in Patients with Advanced Non-Squamous NSCLC Treated with Nivolumab vs Docetaxel in CheckMate 057 (Abstract under Embargo until December 5, 7:00 CET) (Now Available) (ID 4392)

      H. Borghaei

      • Abstract
      • Presentation
      • Slides

      Background:
      Nivolumab significantly improved OS versus docetaxel in patients with previously treated advanced non-squamous NSCLC (CheckMate 057; NCT01673867). Kaplan−Meier OS curves for nivolumab and docetaxel crossed at ~7 months, suggesting non-proportional hazards between arms.

      Methods:
      Post-hoc analyses were conducted to explore relationships between baseline patient/disease characteristics, including PD-L1 expression, and death within the first 3 months of treatment (3motx). Additionally, the association between PD-L1 expression level and magnitude of clinical benefit was explored.

      Results:
      During the first 3motx, risk of death (rDt) was numerically higher with nivolumab versus docetaxel (59 versus 44 deaths among 292 and 290 patients, respectively). Early deaths were most commonly attributed to disease progression (no treatment-related deaths occurred). At 3motx, 80% of nivolumab-treated patients (233/292) and 85% of docetaxel-treated patients (246/290) were alive. After 3motx, the rDt was consistently higher in the docetaxel arm. In univariate analyses, no single baseline factor, including PD-L1 expression, EGFR mutation, ECOG PS, or smoking status, reliably characterized the rDt within the first 3motx with nivolumab. Among patients alive >3 months, the OS HR (95% CI) favored nivolumab in the overall population (0.59 [0.47−0.74]) and PD-L1 non-expressors (PD-L1 expression <1%; 0.66 [0.45−0.97]). In a multivariate analysis, factors associated with higher rDt within the first 3motx on nivolumab versus docetaxel were ECOG PS=1, time since last treatment <3 months, and/or progressive disease as best response to prior treatment combined with lower or no PD-L1 expression. However, the majority of nivolumab-treated patients with these attributes (including PD-L1 non-expressors), did not die within the first 3motx and experienced subsequent benefit. PD-L1 expression was a continuum, ranging from 1 to 100%, with increasing expression associated with enhanced ORR/OS benefit from nivolumab.

      Conclusion:
      In CheckMate 057, the benefit−risk profile of nivolumab versus docetaxel was favorable across the overall patient population. During the first 3motx, a small difference in the number of deaths (n=15) was observed; thereafter the OS rate consistently favored nivolumab (2-year OS was >2-fold higher with nivolumab versus docetaxel). Patients with poorer prognostic factors and/or more aggressive disease combined with lower or no PD-L1 expression appeared to be at higher rDt within the first 3motx on nivolumab versus docetaxel. With the exception of PD-L1 status, these are recognized prognostic factors. While PD-L1 expression may help inform individual treatment decisions, PD-L1 status alone is not considered an appropriate biomarker for nivolumab treatment selection in pre-treated advanced NSCLC, but rather should be considered in the context of other patient/disease characteristics.

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    OA10 - EGFR Mutations (ID 382)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Biology/Pathology
    • Presentations: 1
    • Now Available
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      OA10.04 - Discussant for OA10.01, OA10.02, OA10.03 (Now Available) (ID 7008)

      H. Borghaei

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    P2.03a - Poster Session with Presenters Present (ID 464)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 2
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      P2.03a-018 - A Phase I/II Study of Alisertib, an Oral Aurora Kinase Inhibitor, in Combination with Erlotinib in Patients with Recurrent or Metastatic NSCLC (ID 5197)

      H. Borghaei

      • Abstract

      Background:
      Erlotinib (E) is an oral reversible tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR), known to have efficacy in NSCLC. The aurora kinases are necessary for cell cycle regulation and may have altered function in certain cancers; alisertib (A) is an oral selective aurora kinase A inhibitor. Preclinical data suggested that the combination of an EGFR inhibitor and aurora kinase inhibitor may have synergistic effects in wild-type EGFR NSCLC patients, leading to this phase I/II trial.

      Methods:
      Using a 3 + 3 dose escalation design, A was increased over four dose levels from 30 mg - 50 mg twice daily. E was given daily at 100 mg in DL1 and 150 mg in DL2-4. A was given on days 1-7 of a 21 day cycle along with daily E. Key eligibility criteria: age > 18, histologically confirmed NSCLC, ECOG PS 0-1, prior appropriate first line therapy, acceptable organ function. Key exclusion criteria: EGFR mutation, prior treatment with an EGFR pathway inhibitor or aurora kinase inhibitor.

      Results:
      We report our experience with the phase I portion of this study and plans for the phase II portion. Eighteen patients were treated on four dose levels. Patient characteristics: Median age 61, M/F (8/10), 10/18 had received RT in addition to systemic therapy. 14/18 patients completed at least 2 cycles. Median number of cycles completed was 4.6. Common drug-related AEs of any grade were fatigue (89%), anemia (83%), leukopenia (78%), dyspnea (78%), diarrhea and anorexia (61% respectively). Drug-related Grade 3/4 AE included neutropenia and leukopenia (33% each), febrile neutropenia, lymphopenia and anemia (11% each). Two DLT occurred at DL4 (febrile neutropenia, neutropenia delaying a cycle by > 7 days, both in cycle 1). Disease responses were noted, including one patient with a PR who completed 10 cycles, and 5 patients who achieved SD.

      Conclusion:
      In patients with recurrent/metastatic NSCLC, the combination of A and E was tolerable. However, the maximum administered dose (E 150 mg daily + E 50 mg BID) led to two DLT, thus the MTD was declared at DL3 (E 150 mg + A 40 mg BID); anti-tumor activity was noted. Updated preclinical data from KRAS mutated and WT cell lines indicate activity of this combination in KRAS mutants whereas either drug alone is ineffective. Based on this data, a protocol amendment was submitted to allow only patients with KRAS mutations to be treated in the phase II portion of the study.

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      P2.03a-044 - Severe Adverse Events Impact Overall Survival (OS) and Costs in Elderly Patients with Advanced NSCLC on Second-Line Therapy (ID 5064)

      H. Borghaei

      • Abstract

      Background:
      Among elderly patients with advanced non-small cell lung cancer (aNSCLC), treatment beyond first-line therapy may be associated with higher risk of adverse events (AEs) due to patients’ poorer performance status and higher disease burden and comorbidities. This study assessed the impact of severe AEs during second-line (2L) therapy on OS and cost of care in elderly with aNSCLC.

      Methods:
      Patients aged ≥65 years, diagnosed with aNSCLC between 2007-2011 and receiving 2L chemotherapy/targeted therapy, were identified in the SEER-Medicare database (2006-2013). 57 AEs were identified by literature review and consultation with an oncologist. Severe AEs were operationalized as hospitalizations during which a diagnosis for ≥1 AEs was recorded. OS and all-cause healthcare costs post-initiation of 2L chemotherapy/targeted therapy were compared between patients with and without severe AEs.

      Results:
      Among 3967 patients initiating 2L, 1624 (41%) had ≥1 severe AEs where hypertension (26%), anemia (24%), and pneumonia (23%) were most commonly reported. Patients with and without severe AEs were similar in demographic and cancer characteristics at diagnosis and 2L treatment regimens; although patients with severe AEs had more comorbidities, notably anemia (69% vs 60%). Median OS for patients with severe AEs was almost half of that for patients without severe AEs (6 vs 11 months). After adjustment for potential confounders, patients with severe AEs had more than double risk of death than patients without severe AEs. Cost of caring for patients with severe AEs was more than twice higher than those patients without severe AEs ($16,135 vs $7,559 per-patient-per-month).

      OS With severe AEs cohort N = 1,624 Without severe AEs cohort N = 2,343
      Kaplan-Meier rates (95% CI)
      1 year post 2L initiation 26% (24 - 28) 46% (44 - 48)
      2 years post 2L initiation 11% (9-13) 23% (21-25)
      Median survival time (in months) 6 11
      Adjusted hazard ratio[1] (95% CI) 2.31 (2.16 - 2.47)
      [1] Patients with vs without severe AEs
      AE: adverse event; 2L: second line chemotherapy/targeted therapy; CI: confidence intervals


      Conclusion:
      Occurrence of severe AEs among elderly aNSCLC patients who are receiving 2L chemotherapy/targeted therapy is associated with worse clinical outcomes and a higher economic burden. Results of this analysis suggest that better tolerated therapies may improve outcomes for patients and reduce cost to the healthcare system.

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    P2.03b - Poster Session with Presenters Present (ID 465)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.03b-048 - Access to Biomarker Testing in Patients with Advanced Non-Small Cell Lung Cancer (ID 4461)

      H. Borghaei

      • Abstract

      Background:
      Access to biomarker testing is critical for selecting appropriate treatment for patients with advanced non-small cell lung cancer (aNSCLC). This study assessed rates and patterns of biomarker testing among patients with aNSCLC.

      Methods:
      Patients aged ≥65 years diagnosed with aNSCLC between 2007-2011 were identified in the SEER-Medicare database and were followed for ≥4 months post-diagnosis (n = 9,651). Patients’ first biopsy within ±8 weeks of diagnosis was defined as the index date. Biomarker tests included procedure codes for gene analyses to test for EGFR, ALK, and other mutations. IHC tests, which are mostly used for diagnosis, were excluded. The use of biomarker tests was assessed from the index date until the end of data availability (12/31/2013) or end of Medicare Parts A, B and D eligibility. Analyses were replicated in the subgroup with cancer stages IIIB-T4 or IV and adenocarcinoma, adenosquamous or unknown type of NSCLC histology (n = 6,193).

      Results:
      Of 9,651 patients observed for a median of 11 months, 18% had a biomarker test during the follow-up. The use of biomarker testing increased from 5% in 2007 to 35% in 2011, and was higher among patients who saw a cancer specialist as compared to those who did not see a cancer specialist. When comparing the patients with and without a biomarker test diagnosed in 2011 (i.e., the most recent year in the data) in the full study sample, a higher proportion of patients without a biomarker test were males (51 vs 43%), non-Hispanic Blacks (13 vs 5%), resided in areas with higher poverty (27 vs 15%) and lower education levels (26 vs 17%), and had larger tumors at diagnosis (median 41 vs 38 mm; p <.05 for all). In addition, a lower proportion of them were married (44 vs. 52%), resided in big metropolitan areas (51 vs 57%), had stage IV cancer (64 vs 69%), and adenocarcinoma histology at diagnosis (43 vs. 77%; p <.05 for all). Among tested, >40% of the patients had their first biomarker test >8 weeks after biopsy. Results were similar in the subgroup, but the rate of biomarker testing was slightly higher and with slightly shorter delays.

      Conclusion:
      Among patients with aNSCLC diagnosed in 2007-2011 a substantial proportion did not undergo biomarker testing or had their biomarker test delayed by >8 weeks post-biopsy. Significant differences exist in demographic and cancer characteristics between patients with and without a biomarker test.

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    P2.06 - Poster Session with Presenters Present (ID 467)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
    • Presentations: 1
    • Now Available
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      P2.06-014 - Phase 2 Study of Glesatinib or Sitravatinib with Nivolumab in Non-Small Cell Lung Cancer (NSCLC) after Checkpoint Inhibitor Therapy (Now Available) (ID 4795)

      H. Borghaei

      • Abstract
      • Slides

      Background:
      Combination therapy with agents that target the molecular and cellular mechanisms of resistance to checkpoint inhibitor therapy (CIT) is a rational approach to restoring or improving the efficacy of CIT in patients with immunotherapy resistant NSCLC. Glesatinib, a tyrosine kinase inhibitor (TKI), which targets Axl, MER and MET RTKs expressed on macrophages and antigen-presenting-cells within the tumor microenvironment (TME), may reverse the immunosuppressive TME and enhance anti-tumor T and NK cell responses by enhancing antigen presentation and T cell effector function. Sitravatinib, also a TKI, which targets VEGFR2 and KIT as well as Axl, MER and MET, may further enhance anti-tumor activity by VEGFR2 and KIT inhibition mediated reduction of regulatory T cells and myeloid-derived suppressor cells (MDSCs). Given these pleiotropic immune activating effects, the combination of glesatinib or sitravatinib with nivolumab is a rational approach to restoring or enhancing the clinical activity of CIT in patients with immunotherapy resistant NSCLC.

      Methods:
      This open-label Phase 2 study evaluates the tolerability and clinical activity of the investigational agents, glesatinib or sitravatinib in combination with nivolumab in separate cohorts of patients with non-squamous NSCLC who have experienced progression of disease on or after treatment with CIT. The study begins with a limited dose escalation evaluation of each investigational agent in combination with nivolumab to determine the dose levels to be used in Phase 2. The primary objective is to assess the clinical activity of the combination regimens using the Objective Response Rate (ORR) by RECIST 1.1. Other objectives include safety, tolerability, pharmacokinetics and changes in circulating and tumor cell PD-L1, circulating and tumor infiltrating immune cell populations, cytokines and gene expression signatures. Enrollment into each Phase 2 treatment arm is stratified by prior outcome of CIT (e.g., clinical benefit versus progression of disease in ≤12 weeks). The investigational agents are administered orally in continuous regimens; nivolumab is administered intravenously, 3 mg/kg every 2 weeks. The sample sizes for the treatment arms are based on two-stage Simon Optimal Designs. Status: The US IND opened in June 2016.

      Results:
      Section not applicable

      Conclusion:
      Section not applicable

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