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M. Reck

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    ESMO-IASLC Best Abstracts (ID 48)

    • Event: ELCC 2017
    • Type: Best abstracts session
    • Track:
    • Presentations: 6
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      Invited Discussant 81O and 82O (ID 552)

      16:45 - 18:15  |  Author(s): S. Peters

      • Abstract
      • Slides

      Abstract not provided

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      Invited Discussant LBA1 and 147O (ID 553)

      16:45 - 18:15  |  Author(s): A.G. Nicholson

      • Abstract
      • Slides

      Abstract not provided

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      147O - Correlation of molecular status and anatomic sites of metastases (mets) at diagnosis (Dx) of non-small cell lung cancer (NSCLC) (ID 243)

      16:45 - 18:15  |  Author(s): C. Kuijpers, L. Hendriks, J. Derks, A. Dingemans, A. Van Lindert, M. Van den Heuvel, R. Damhuis, S. Willems

      • Abstract
      • Presentation
      • Slides

      Background:
      Non-squamous (ns)-NSCLC is often driven by (targetable) molecular alterations, such as EGFR mutations (EGFR+), KRAS mutations (KRAS+), or ALK translocation (ALK+). Patterns of mets may differ between alterations, which may have implications for mets screening or treatment decisions. We assessed in a nationwide stage IV ns-NSCLC cohort whether molecular status is associated with anatomic sites of mets sites at Dx.

      Methods:
      All patients (pts) with stage IV ns-NSCLC from 2013, without a recent history of cancer, were identified from the Netherlands Cancer Registry, in which anatomic sites of mets before treatment initiation are recorded. Tumors were matched to the Dutch Pathology Registry (PALGA), and data on molecular testing (EGFR, KRAS, ALK) were extracted. Correlation between molecular status and anatomic sites of mets was assessed. Multivariable logistic regression analyses were performed to calculate adjusted odds ratios (OR) with 95% confidence intervals (CI).

      Results:
      In total, 2884 pts with stage IV ns-NSCLC were identified. Included for analysis were: EGFR + (n = 220; 7.6%), KRAS + (n = 775; 26.9%), ALK + (n = 42; 1.5%) and triple-negative (n = 1117; 38.7%). Most frequent mets sites were bone (33.7%), lung (23.6%), pleura (23.4%), and brain (22.5%). EGFR+ tumors significantly more often had bone mets (49.1%) than KRAS + (OR 2.01, 95% CI 1.48-2.72), ALK + (OR 2.22, 95% CI 1.09-4.50), and triple-negative tumors (OR 2.09, 95% CI 1.56-2.81). Compared to triple-negative tumors, EGFR+ tumors more often had metastasized to the pleura (OR 1.50, 95% CI 1.08-2.08) and liver (OR 1.52, 95% CI 1.00-2.25), and less often to the brain (OR 0.67, 95% CI 0.45-0.99) and adrenal gland (OR 0.49, 95% CI 0.31-0.79). KRAS+ and ALK+ tumors significantly more often had metastasized to the lung (OR 1.35, 95% CI 1.09-1.68) and liver (OR 2.09, 95% CI 1.00-4.35) than triple-negative tumors.

      Conclusions:
      Molecular status of NSCLC is associated with biological behavior. At diagnosis, 49.1% of EGFR+ pts had bone mets. In particular, because EGFR+ pts have a notably better prognosis, screening for and prevention of skeletal-related events in NSCLC pts with an EGFR mutation is reasonable.

      Clinical trial identification:


      Legal entity responsible for the study:
      University Medical Centre Utrecht

      Funding:
      The research is sponsored by Roche and Pfizer.

      Disclosure:
      C. Kuijpers, S. Willems: The research is sponsored by Roche and Pfizer. A-M. Dingemans: Attended advisory boards from Roche, Lilly, Clovis, AstraZeneca, MSD, Boehringer Ingelheim, fees were paid to institute. All other authors have declared no conflicts of interest.

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      81O - Safety and efficacy analyses of atezolizumab in advanced non-small cell lung cancer (NSCLC) patients with or without baseline brain metastases (ID 316)

      16:45 - 18:15  |  Author(s): R.V. Lukas, M. Gandhi, C. O’hear, S. Hu, C. Lai, J.D. Patel

      • Abstract
      • Presentation
      • Slides

      Background:
      ≈ 20%-40% patients (pts) with advanced NSCLC develop brain metastases (mets), which are associated with poor survival. Atezolizumab (atezo; anti–PD-L1) monotherapy has shown clinical benefit in pts with NSCLC regardless of PD-L1 expression status. Here we compare the safety and efficacy of atezo in NSCLC pts with or without baseline brain mets.

      Methods:
      Safety analyses were conducted on pts who received atezo as 2L+ treatment in 5 studies: PCD4989g, BIRCH, FIR, POPLAR and OAK. Pts had previously treated stable/asymptomatic or no brain mets at baseline. Efficacy analyses were conducted on pts in the atezo and docetaxel (doc) arms of OAK.

      Results:
      The pooled safety cohort included 1452 pts; 79 (5%) had brain mets. The incidence of all AEs and SAEs was similar in pts with or without brain mets (Table). A numerically higher rate of neurological AEs and SAEs was reported in pts with vs those without brain mets. No treatment-related G4-5 neurological AEs or SAEs were seen in pts with brain mets. The most common treatment-related neurological AE was headache in 6 (8%) pts with and 42 (3%) pts without brain mets. Efficacy cohort included the first 850 pts with or without brain mets from OAK who were randomized to atezo or doc. Atezo showed survival benefit vs doc in pts with brain mets (HR = 0.54, 95% CI: 0.31, 0.94; mOS 20.1 mo [n = 38] vs 11.9 mo [n = 47] with atezo vs doc) as well as in pts without brain mets (HR = 0.75, 95% CI: 0.63, 0.89; mOS 13.0 mo [n = 387] vs 9.4 mo [n = 378] with atezo vs doc). The risk of developing new CNS lesions appeared to be lower with atezo vs doc (HR = 0.42, 95% CI: 0.15, 1.18; median time to develop new CNS lesion, not reached vs 9.5 mo) in pts with baseline brain mets.

      Conclusions:
      Atezo demonstrated an acceptable safety profile and encouraging survival benefit in pts with NSCLC who had previously treated stable/asymptomatic brain mets. Results of this analyses warrant further investigation of atezo in advanced NSCLC pts with CNS mets.rnTable: 81OSummary of safety data in advanced NSCLC patients with and without baseline brain metastases following atezolizumab as 2L+ treatmentrn

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
      SafetyPooled cohort[a] (N = 1452)
      Patients with baseline brain mets (n = 79) n (%)patients without baseline brain mets (n = 1373) n (%)
      Any AE75 (95%)1261 (92%)
      Any neurological AE37 (47%)414 (30%)
      Treatment-related AEs55 (70%)876 (64%)
      Treatment-related neurological AEs14 (18%)128 (9%)
      Any SAE26 (33%)492 (36%)
      Any neurological SAEs5 (6%)36 (3%)
      Treatment-related SAEs7 (9%)135 (10%)
      Treatment-related neurological SAEs07 (0.5%)
      Discontinued treatment due to AE8 (10%)99 (7%)
      rnaFrom PCD4989g (NCT01375842), BIRCH (NCT02031458), FIR (NCT01846416), POPLAR (NCT01903993) and OAK (NCT02008227) trials.rn

      Clinical trial identification:
      NCT01375842, NCT02031458, NCT01846416, NCT01903993, NCT02008227

      Legal entity responsible for the study:
      F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

      Funding:
      F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

      Disclosure:
      R.V. Lukas: Advisory board (2016) for Astra-Zeneca and advisory Board (2013) for Novocure. M. Gandhi: Genentech employee. C. O’Hear: Employee of Genentech and have stock in Roche. S. Hu: Employee and stockholder in Roche. C. Lai: Employee of and have stock in Roche. All other authors have declared no conflicts of interest.

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      82O - Durvalumab in ≥ 3rd-line EGFR mutant/ALK+, locally advanced or metastatic NSCLC: Results from the phase 2 ATLANTIC study (ID 263)

      16:45 - 18:15  |  Author(s): M. Garassino, B. Cho, J.E. Gray, J. Mazières, K. Park, R.A. Soo, P. Dennis, Y. Huang, C. Wadsworth, N. Rizvi

      • Abstract
      • Presentation
      • Slides

      Background:
      Anti-PD-1/PD-L1 therapies have demonstrated meaningful clinical benefit in pts with EGFR/ALK wild-type (WT) advanced NSCLC. However, to our knowledge these agents have never been investigated in a study prospectively focusing on NSCLC pts with EGFR mutations or ALK alterations (EGFRmut/ALK+), a distinct subgroup with clear biological and treatment outcome differences compared with EGFR/ALK WT pts. Durvalumab is an engineered human IgG1 mAb targeting PD-L1.

      Methods:
      ATLANTIC (NCT02087423) was a Phase 2, open-label, single-arm trial in pts with locally advanced or metastatic Stage IIIB–IV NSCLC (WHO PS 0 or 1; ≥2 prior systemic regimens, including 1 platinum-based and 1 TKI [EGFRmut/ALK+ pts]). There was no maximum number of prior treatments. The study initially enrolled all-comers and then was restricted to pts with PD-L1 high tumours (≥25% of tumour cells with membrane staining). The study included 3 pt cohorts defined by EGFR/ALK status and tumor PD-L1 expression; here we report results from EGFRmut/ALK+ pts (Cohort 1). The primary outcome was ORR (RECIST v1.1). Secondary outcomes included DCR, DoR, PFS, OS, and safety (CTCAE v4.03).

      Results:
      As of 3 June 2016, 111 pts (median age 61 years, 63% female, 59% WHO PS 1, 99% non-squamous histology; 59% never smokers; mean prior therapies 3.8) had received durvalumab (10 mg/kg i.v. q2w for ≤12 months). Responses were durable. Most AEs were low grade. Immune-mediated AEs were manageable with standard treatment guidelines; 5.4% of pts had Grade ≥3 treatment-related (TR) AEs and 0.9% had TRAEs leading to discontinuation.rnTable: 82Orn

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn
      rnPD-L1 high (≥25%)PD-L1 low/negative (<25%)
      n = 74[a]n = 28[a]
      ORR,[b] % (95% CI)12.2 (5.7, 21.8)3.6 (0.1, 18.3)
      DCR, % (95% CI)20.3 (11.8, 31.2)7.1 (0.9, 23.5)
      mDoR, months (95% CI)7.4 (5.4, 9.2)NC[c]
      rnn = 77[d]n = 30[d]
      mPFS, months (95% CI)1.9 (1.8, 3.6)1.9 (1.8, 1.9)
      mOS, months (95% CI)13.3 (8.1, NC)9.9 (4.2, 13.0)
      1-year OS, % (95% CI)54.8 (41.5, 66.3)40.0 (22.1, 57.4)
      mFollow-up for OS, months6.58.2
      rnNote: 4 patients had PD-L1 expression unknown or missing.rnaFull analysis set - evaluable for response per independent central review (ICR).rnbConfirmed response per ICR.rncNot calculated due to small number of responders.rndFull analysis set.rnDCR=disease control rate (complete response, partial response or stable disease ≥24 weeks); DoR=duration of response; m=median; NC=not calculated; ORR=objective response rate; OS=overall survival; PFS=progression-free survivalrn

      Conclusions:
      Although the ORR was somewhat lower compared with that reported in Cohort 2 (EGFR/ALK WT), durable responses were still observed in this heavily pretreated metastatic EGFRmut/ALK+ NSCLC population. However, the data were limited by the short duration of follow up and further confirmation is needed. Activity was greater for pts with high PD-L1 expression. The tolerability profile was manageable.

      Clinical trial identification:
      NCT02087423 (March 4, 2014)

      Legal entity responsible for the study:
      AstraZeneca PLC

      Funding:
      AstraZeneca

      Disclosure:
      M.C. Garassino: Grants/research support: Pfizer; Consultant: Eli Lilly; AZ, BMS, MSD, Roche, Celgene. B-C. Cho: Grants/Research: AZ, BI, Yuhan, Roche, MSD, BMS Ono, Eli Lilly, Pfizer, Bayer Consultant: AZ, BI, Yuhan, Roche, MSD, BMS Ono, Eli Lilly, Pfizer Honoraria: AZ, BI, Yuhan, Roche, MSD, BMS Ono, Eli Lilly, Pfizer. J. Mazières: Advisory board: AZ. K. Park: Advisory role: Astellas, AZ, BI, Clovis, Lilly, Hanmi, AZ, Kyowa Hakko Kirin, Novartis, Ono, Roche Speaker bureau: BI Research: AZ. R.A. Soo: Grants/research support: AZ Honoraria: AZ, BI, BMS, Lilly, Pfizer, Roche, Taiho, Novartis, Merck. P. Dennis, Y. Huang: Employment: AZ. C. Wadsworth: Employment: AZ; Stock ownership: AZ. N. Rizvi: Consulting: AZ, Roche, Novartis, Merck, Pfizer, Lilly, AZ, BMS, Merck Stock ownership: Gritstone Oncology. All other authors have declared no conflicts of interest.

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      LBA1 - Establishment of a diagnostic algorithm for ROS1 testing in Canada (ID 480)

      16:45 - 18:15  |  Author(s): M.S. Tsao, E. Torlakovic, G. Bigras, H. Wang, G. Qing, C.C. Cheung, Z. Xu, C. Couture, D. Ionescu, A. Smith

      • Abstract
      • Presentation
      • Slides

      Background:
      The ROS1 fusion tyrosine kinase that results from rearrangements of the ROS1 gene is a new targetable driver oncogene. It is detected in 1-2% of lung adenocarcinoma patients. Crizotinib recently received US FDA approval for the treatment of patients with lung cancer carrying ROS1 rearrangements. Fluorescent in situ hybridization (FISH) is the gold standard for detecting ROS1 rearranged tumors. Immunohistochemistry (IHC) has been considered as a screening assay to identify ROS1 rearranged lung cancers. However, published reports suggested that ROS1 IHC shows high sensitivity but moderate specificity, thus resulting in a high percentage of cases that require confirmatory FISH testing. This may negatively impact on the cost of ROS1 screening by IHC.

      Methods:
      Sensitive and highly specific IHC protocols for ROS1 testing using D4D6 antibody (Cell Signaling, Danver, MA) on the Ventana and Dako autostainers were developed. A FISH protocol for detecting ROS1 gene rearrangements using a ROS1 (6q22) Break Apart FISH Probe (Biocare, Concord, CA) was also established. A network of 14 pathology laboratories participated in the validation of these protocols to detect ROS1 rearranged lung cancers. Validation involved 9 confirmed ROS1 FISH positive (+) and 15 ROS1 FISH negative (-) tumor samples.

      Results:
      Among 10 laboratories that completed FISH testing, 11 (4.6%) of 240 tests failed. The overall sensitivity of the laboratories to detect FISH+ cases was 88.9% (80/90), and the misclassification rate was 3.5% (8/229). Among 11 laboratories that completed the IHC testing, results from 14/264 (5.3%) tests were unavailable. Using the H-score cut-off of 80 (that completely distinguished between the mean H-score of FISH+ and FISH- cases), the overall sensitivity to detect FISH+ sample was 97%, with 94% specificity, 91% positive predictive value, and 98% negative predictive value. Eight laboratories achieved 100% sensitivity; only one laboratory had specificity below 90%. ROS1 IHC positive tumor showed homogeneous staining in practically all tumor cells.

      Conclusions:
      This pan-Canadian consortium established the criteria to enable clinical implementation of IHC screening and FISH testing for ROS1 rearranged lung cancers using optimized protocols with high sensitivity and specificity.

      Clinical trial identification:


      Legal entity responsible for the study:
      University Health Network

      Funding:
      Pfizer Canada

      Disclosure:
      M.S. Tsao: Received advisory board honoraria and research grant from Pfizer Canada, AstraZeneca, Merck Canada. Received advisory board honoraria from Bristol-Myers Squibb, Hoffmann La Roche and Boehringer Ingelheim Canada. E. Torlakovic: Received advisory board honoraria from Pfizer Canada, Merck Canada, Bristol-Myers Squibb. G. Bigras: Received advisory board honoraria from Pfizer Canada, Merck Canada, Bristol-Myers Squibb. H. Wang: Received advisory board honoraria from Pfizer Canada, Merck Canada, Bristol-Myers Squibb and Hoffmann La Roche Canada. G. Qing: Received advisory board honoraria from Pfizer Canada, Merck Canada, Bristol-Myers Squibb. C.C. Cheung: Received advisory board honoraria from Merck Canada and Bristol-Myers Squibb. Z. Xu: Received advisory board honoraria from Pfizer Canada, Merck Canada, Bristol-Myers Squibb, Hoffmann La Roche. C. Couture, D. Ionescu: Received advisory board honoraria from Pfizer Canada, AstraZeneca, Merck Canada, Bristol-Myers Squibb, Hoffmann La Roche. A. Smith: Received advisory board honoraria from Pfizer Canada

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Author of

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    Poster Display Session (ID 63)

    • Event: ELCC 2017
    • Type: Poster Display Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1
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      119P - A phase 2 randomized open-label study of ramucirumab (RAM) plus first-line platinum-based chemotherapy in patients (pts) with recurrent or advanced non-small cell lung cancer (NSCLC): Final results from squamous pts (ID 174)

      12:30 - 13:00  |  Author(s): M. Reck

      • Abstract

      Background:
      Vascular endothelial growth factor receptors (VEGFR) and their ligands are key regulators of angiogenesis and implicated in pathogenesis of NSCLC. RAM, a human IgG1 monoclonal antibody, specifically binds to VEGFR-2 thereby preventing receptor activation and angiogenesis. In a phase 2 trial (NCT01160744) addition of RAM to platinum-pemetrexed chemotherapy demonstrated clinical activity and acceptable safety in pts with advanced non-squamous NSCLC; here we report data from squamous (SQ) NSCLC pts treated with RAM in combination with first-line gemcitabine plus platinum chemotherapy.

      Methods:
      Eligible pts had Stage IV SQ NSCLC, ECOG PS ≤ 2, and no prior VEGF/VEGFR therapy nor chemotherapy for stage IV disease. Pts were randomized 1:1 into either Arm C: gemcitabine 1000 mg/m[2] + carboplatin AUC=5/cisplatin 75 mg/m[2] (GEM + Cb/Cis) or Arm D: ramucirumab 10 mg/kg + gemcitabine + carboplatin/cisplatin (RAM + GEM + Cb/Cis). Pts received first-line therapy from 4 to 6 cycles (21-day cycle); patients in Arm D, in absence of progressive disease, entered a maintenance phase with RAM alone. Primary objective was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), change in tumor size (CTS), duration of response and safety.

      Results:
      140 pts were randomized (GEM + Cb/Cis: 69; RAM + GEM + Cb/Cis: 71). The median PFS was 5.4 m GEM + Cb/Cis and 5.6 m for RAM + GEM + Cb/Cis; HR 0.88 (90% CI, 0.64, 1.22; p = 0.52). Median OS was 11.3 m for GEM + Cb/Cis and 10.4 m for RAM + GEM + Cb/Cis; HR 0.93 (90% CI, 0.68, 1.27; p = 0.68). ORR was significantly improved in RAM + GEM + Cb/Cis (46.5%) compared to GEM + Cb/Cis (24.6%) (p = 0.007). No statistically significant difference was observed in DCR and CTS between the two arms. Grade ≥ 3 adverse events occurring in > 10% of pts on RAM administered arm were: anemia, neutropenia and thrombocytopenia.

      Conclusions:
      The primary endpoint of PFS was not met. The addition of RAM to GEM + Cb/Cis significantly improved ORR in pts with SQ NSCLC with no new unexpected safety findings.

      Clinical trial identification:
      NCT01160744 JVBL

      Legal entity responsible for the study:
      Eli Lilly and Company, Indianapolis, IN

      Funding:
      Eli Lilly and Company, Indianapolis, IN

      Disclosure:
      R.C. Doebele: Grants from Ignyta, Threshold Pharmaceuticals, Strategia; patent from NTRK1 FISH; royalties paid to Abbott Molecular; Licensing fees for biologic materials Ariad, Loxo, Chugai, Blueprint Medicines; other from Ariad, Trovagene, Guardant Health, AstraZeneca. D. Spigel: Novartis Speakers Bureau (uncompensated). M. Tehfe: Advisory board committee and Honoraria for speaker: Lilly, Celegene, BMS, Merck. M. Reck: Personal fees from Boehringer-Ingelheim, Hoffmann-La Roche, Lilly, MSD, BMS, AstraZeneca, Celgene, Merck, Pfizer, outside the submitted work. A. Zimmermann, E. Alexandris, P. Lee: Employee and stockholder of Eli Lilly and Company. P. Bonomi: Personal fees from Eli Lilly, Roche Genentech, Pfizer, Celgene, Bristol Myers Squibb, Astra Zeneca, Merck, outside the submitted work. All authors have declared no conflicts of interest.