Virtual Library

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    ESMO-IASLC Best Abstracts (ID 48)

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

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

      • Abstract
      • Slides

      Abstract not provided

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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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      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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      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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    Heine H. Hansen Award Lecture (ID 1)

    • Event: ELCC 2017
    • Type: Keynote Lecture
    • Track:
    • Presentations: 1
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      The Heine Hansen legacy: How can we improve lung cancer research and practice? (ID 1)

      13:45 - 14:15  |  Author(s): R. Dziadziuszko

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    Immunotherapies and targeted therapies in advanced NSCLC (ID 39)

    • Event: ELCC 2017
    • Type: Proffered Paper session
    • Track:
    • Presentations: 6
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      83O - A phase II study of durvalumab (MEDI4736) for previously treated patients with stage IV squamous NSCLC (SqNSCLC): Lung-MAP Sub-study SWOG S1400A (ID 279)

      14:45 - 16:15  |  Author(s): V. Papadimitrakopoulou, M.W. Redman, H. Borghaei, S.N. Waqar, F. Robert, G.J. Kiefer, S. McDonough, R.S. Herbst, K. Kelly, D.R. Gandara

      • Abstract
      • Presentation
      • Slides

      Background:
      Durvalumab (MEDI4736) is an engineered human IgG1 mAb targeting programmed cell death ligand-1 (PD-L1). Treatment with other anti-PD-1/PD-L1 antibodies has demonstrated meaningful clinical benefit in patients with advanced NSCLC.

      Methods:
      As part of the Lung Master Protocol S1400, a National Clinical Trials Network group "umbrella" trial for second-line SqNSCLC we conducted a phase II study of durvalumab in patients with Stage IV squamous NSCLC (ECOG PS 0-2; ≥1 prior systemic treatment regimens, including one platinum-based), EGFR/ALK wild-type. The primary endpoint was overall response rate (ORR) (RECIST v1.1); secondary endpoints included duration of response (DoR), ORR among PD-L1 positive patients, disease control rate (DCR), investigator-assessed progression-free survival (PFS), overall survival (OS) and safety (CTCAE v4.03). The initial protocol was a randomized phase II/III comparison of durvalumab to docetaxel, and was amended to be a single arm phase II trial of single agent durvalumab. PD-L1 positive tumors were defined by ≥ 25% of tumor cells with membrane staining.

      Results:
      Of the 68 eligible patients (median [range] age 66 [35-92] years, PS 0/1/2 26%/62%/12%), 11 were responders (16% ORR, 95% Confidence Interval [CI] 7%, 25%). DCR was 54% (CI 43%, 66%), median OS was 11.5 months (CI 10.1-12.4 mos), and median PFS was 2.9 mos (CI 2.0-4.1 mos). Of the 11 responders, median time to response and DoR were 3.6 mos (CI 2.8-4.2 mos) and 18.6 months (95% CI 4.4-NR mos), respectively. Of the 14 PDL1-positive patients, 2 were responders (14% ORR, 95% CI 0%, 33%), DCR was 57% (CI 31%, 83%), median OS and PFS were 10.7 mos (CI 9.2-10.7 mos) and 2.3 mos (CI 1.4-4.9 mos), respectively. Durvalumab showed a manageable safety and tolerability profile; most adverse events (AEs) were low grade and resolved with treatment delay and/or immunosuppressive interventions. Grade ≥3 treatment-related AEs occurred in 23(34%) of patients. Drug-related AEs led to discontinuation in 6 patients (9%, 95% CI 2%, 16%).

      Conclusions:
      Durvalumab demonstrated clinical benefit and durable responses in a previously treated metastatic NSCLC population with manageable toxicity profile. Results are comparable with other anti-PD-1/PD-L1 therapies in metastatic, relapsed NSCLC.

      Clinical trial identification:
      NCT02766335

      Legal entity responsible for the study:
      Southwest Oncology Group/NCTN

      Funding:
      Lung-MAP supported in part by NIH/NCI grants CA180888, CA180819, CA180820, CA180821, CA180868, and by Amgen, AstraZeneca, Bristol-Myers Squibb Company Genentech and Pfizer through the Foundation for the National Institutes of Health, in partnership with Friends of Cancer Research.

      Disclosure:
      V. Papadimitrakopoulou: Advisory Role for: Eli Lilly&Co, Genentech, Janssen Global Sevices, Bristol-Myers Squibb, ARIAD, Astra Zeneca Pharmaceuticals, Novartis, Merck Corporate-sponsored research: Novartis, Astra Zeneca, Genentech, Merck, Janssen, ACEA, Bristol-Myers Squibb. H. Borghaei: Advisory: Bristol-Myers Squibb, Lilly, Genentech, Celgene, Pfizer, EMD-Serono, Boerhinger-Ingelheim, Trovagene, AstraZeneca, Research Support: Millenium, Merck, Celgene. K. Kelly: Advisory: Synta, AstraZeneca, Lilly, Clovis Oncology, ARIAD, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, G1 Therapeutics. Research: Millenium, Novartis, EMD Serono, Lilly, Genentech, Abbvie, Gilead, Celgene, Five Prime Therapeutics, Transgene. All other authors have declared no conflicts of interest.

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      84O - Atezolizumab as first-line (1L) therapy for advanced non-small cell lung cancer (NSCLC) in PD-L1–selected patients: Efficacy data from the BIRCH trial (ID 367)

      14:45 - 16:15  |  Author(s): S. Peters, E. Carcereny Costa, M.C. Garassino, D. Christoph, T. Kurata, J. Chaft, M.L. Johnson, S. Mocci, S.N. Gettinger, E. Felip

      • Abstract
      • Slides

      Background:
      Atezolizumab (atezo) inhibits binding of PD-L1 to its receptors, PD-1 and B7.1, restoring tumor-specific T-cell immunity and leaving the PD-L2/PD-1 interaction intact. This single-arm Phase II study (BIRCH; NCT02031458) was designed to evaluate atezo monotherapy in PD-L1–selected patients with advanced NSCLC. A previous analysis (median follow-up, 8.5 months) demonstrated clinical activity in chemotherapy-naive 1L and 2L+ PD-L1–selected patients. Here we present updated efficacy data for 1L patients.

      Methods:
      Eligible patients had PD-L1–selected advanced-stage NSCLC, with no prior chemotherapy or CNS metastases. PD-L1 was centrally evaluated using the VENTANA SP142 IHC assay. Enrolled patients expressed PD-L1 on ≥ 5% of tumor cells (TC) or tumor-infiltrating immune cells (IC), ie, TC2/3 or IC2/3. Those with EGFR mutation or ALK rearrangement must have had prior treatment with an appropriate TKI. Atezo was administered (1200 mg IV q3w) until radiographic disease progression or unacceptable toxicity. The primary endpoint was independent review facility (IRF)–assessed ORR; secondary endpoints included investigator (INV)-assessed ORR, DOR, PFS (RECIST v1.1) and OS.

      Results:
      With a median duration of survival follow-up of 22.5 months, INV-assessed ORR was 25% in TC2/3 or IC2/3 (all treated) patients and 34% in TC3 or IC3 patients (Table). Median OS was 23.5 months in all treated patients and 26.9 months in the TC3 or IC3 subgroup. Responses were observed in both EGFR and KRAS mutant and wild-type tumors. The safety profile was consistent with previous atezo NSCLC studies.

      Conclusions:
      With a median follow-up of 22.5 months, atezo continued to demonstrate durable clinical benefit in 1L NSCLC, in both EGFR and KRAS mutant and wild-type tumors. These results support ongoing Phase III trials evaluating atezo vs chemotherapy in 1L NSCLC.rnTable: 84Orn

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
      Endpoint (95% CI)TC3 or IC3[a] (n = 65)TC2/3 or IC2/3[b] (n = 138)
      INV ORR, %34%25%
      (22.6-46.7)(18.4-33.5)
      EGFR mutant/wild type, ORR, %25%/31%31%/22%
      KRAS mutant/wild type, ORR, %38%/30%31%/22%
      Median DOR, moNE16.5
      (8.5-NE)(9.9-NE)
      Median OS, mo26.923.5
      (12.0-NE)(18.1-NE)
      12-mo OS rate, %61.5%66.4%
      (49.0-74.0)(58.1-74.6)
      Median PFS, mo7.37.3
      (4.9-12.0)(5.7-9.7)
      12-mo PFS rate, %36.5%32.5%
      (24.0-48.9)(24.2-40.8)
      rnNE, not estimable.rnaTC ≥ 50% or IC ≥ 10% PD-L1–expressing cells.rnbTC or IC ≥ 5% PD-L1–expressing cells.rn

      Clinical trial identification:
      NCT02031458

      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:
      M.C. Garassino: Honoraria, Consulting, Speaker\'s Bureau, research funding, expert testimony, travel expenses: MSD, BMS, AZ, Lilly, Roche. D. Christoph: Honoraria, Speaker\'s Bureau: BI, BMS, Chugai, Novartis, Merck, MSD, Pfizer, Roche; Consulting: BI, BMS, Novartis, Pfizer, Roche; Expert testimony: BI, BMS, Novartis, Pfizer, Roche. J. Chaft: Advisor for Genentech and Astra Zeneca. M.L. Johnson: Consulting: Genentech, Celgene, BI; Research funding: OncoMed, BerGenBio, Lilly, EMD Serono, Kadmon, Janssen, Mirati, Genmab, Pfizer, AZ, Roche/Genentech, Stemcentrix, Novartis, Checkpoint, Array, Regeneron. S. Mocci: Employee, stock: Roche/Genentech. S.N. Gettinger: Consulting: BMS; Research funding: Roche/Genentech, BMS, ARIAD, Incyte, Celldex. E. Felip: Advisory Boards: Lilly, Pfizer, BI, MSD, Roche; Speaker\'s Bureau: AZ, BMS, Novartis. All other authors have declared no conflicts of interest.

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      2O - Favorable clinical outcome and response to immunotherapy share a common PD-L1/PD-1 based NSCLC immune contexture (ID 400)

      14:45 - 16:15  |  Author(s): G. Mazzaschi, D. Madeddu, G. Bocchialini, L. Gnetti, G. Armani, F. Sogni, M. Tiseo, A. Ardizzoni, F. Aversa, F. Quaini

      • Abstract
      • Presentation
      • Slides

      Background:
      The success of PD-1/PD-L1 immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. According to PD-L1 status and number of Tumor Infiltrating Lymphocytes (TILs), the cancer microenvironment can be classified into four types reflecting immune resistance, ignorance, induction and tolerance. However, an extended tissue characterization of the immune contexture and its predictive/prognostic value in NSCLC remain elusive. The aim of the present investigation was to determine whether immunologically defined classes of NSCLC differentially impact on clinical outcome.

      Methods:
      Histologic sections of NSCLC samples surgically removed to untreated 51 ADC and 69 SCC and 8 ADC and 10 SCC patients receiving Nivolumab were included. PD-L1 (clones 28-8 and SP142) was measured by immunoperoxidase (H-score) and immunofluorescence (QIF). The n/mm[2] and intra-, peri-tumor or invasive margin localization of TILs subpopulations were computed establishing cut off values relative to each phenotype. Immunohistochemical data and clinical records were subjected to Kaplan Meier analysis.

      Results:
      ADC cases had 2-fold higher CD3[pos] and 1.8-fold lower CD4[pos] cells compared to SCC and TILs-rich ADC had 10 months’ increase in OS vs –poor (p < 0.01). EGFR mutation conditioned a lower intratumor density of TILs. The frequency of type I (PD-L1[high] TILs[high]) contexture was low (14.6%) while > 1/3 of NSCLC samples displayed type II (PD-L1[low/neg] TILs[low]), reflecting immune exhaustion. The proportion of type III (PD-L1[high] TILs[low]) and IV (PD-L1[low/neg] TILs[high]) immune categories, with relatively increased Nks and Tregs, was similar. NSCLC type III had the highest OS (35.5 mos.) and PFS (25.7) while in type II immune ignorant cases OS and PFS were respectively 21.7 and 12. Independently from immune categories, patients with PD-1[low] and high CD8/CD3 ratio had 11 mos. gain in OS (p < 0.01) compared to the reverse counterpart. Accordingly, PD-L1[high] and PD-1[low] characterized 86% of patients responsive to nivolumab.

      Conclusions:
      In a dynamic PD-L1 milieu a concomitant intrinsic or therapeutically induced decay of PD-1 receptor allows TILs to escape from PD-L1 pressure and delays tumor progression, improving OS.

      Clinical trial identification:


      Legal entity responsible for the study:
      University Hospital of Parma, Medicine

      Funding:
      University of Parma

      Disclosure:
      All authors have declared no conflicts of interest.

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      Invited Discussant 83O, 84O and 2O (ID 526)

      14:45 - 16:15  |  Author(s): L. Paz-Ares

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      85O_PR - Patient-reported symptoms and impact of treatment with osimertinib vs chemotherapy for advanced non-small cell lung cancer (ID 373)

      14:45 - 16:15  |  Author(s): C.K. Lee, S. Novello, A. Ryden, A. Templeton, K. Rüdell, H. Mann, S. Ghiorghiu, T. Mok

      • Abstract
      • Slides

      Background:
      We assessed self-reported symptoms of advanced non-small cell lung cancer patients treated with osimertinib 80mg or chemotherapy in the AURA3 phase III clinical trial (NCT02151981).

      Methods:
      Patients completed the European Organisation for Research and Treatment of Cancer QLQ-LC13 questionnaire on disease-specific symptoms and QLQ-C30 on general cancer symptoms, functioning and global health status. QLQ-LC13 was completed at baseline, weekly for 6 weeks, then 3-weekly up to end of study, and at progression. QLQ-C30 was completed at baseline, then 6-weekly up to end of study, and at progression. We compared for differences between treatments in time to deterioration and odds of improvement of symptoms (two assessments ≥18 days apart). A deterioration or improvement was defined as a change in score from baseline of ≥ +/-10. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using a log-rank test stratified by ethnicity. Odds ratios (OR) and 95% CIs were calculated using logistic regression adjusted for ethnicity.

      Results:
      At baseline, 215 − 228 of 279 (77 − 82%) patients on osimertinib and 106 − 114 of 140 (76 − 81%) on chemotherapy had QLQ-LC13 scores ≤90 (cut-off to have potential for deterioration) for cough, chest pain and dyspnoea. Time to deterioration of key symptoms was longer with osimertinib than with chemotherapy (Table). The proportion of patients with improvement in global health status was higher with osimertinib (80/215 [37%]) than with chemotherapy (23/105 [22%]; OR: 2.11; 95% CI: 1.24, 3.67; p = 0.007), as it was for appetite loss (OR: 2.50; 95% CI: 1.31, 4.84) and fatigue (OR: 1.96; 95% CI: 1.20, 3.22).rnTable: 85O_PRTime to deterioration of selected key symptomsrn

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn
      SymptomTreatmentNumber (%) of patients with eventHR (95% CI)p-value
      CoughO99 (46.0)0.74 (0.53, 1.05)0.090
      C58 (54.7)
      Chest painO99 (43.8)0.52 (0.37, 0.73)<0.001
      C66 (58.4)
      DyspnoeaO122 (53.5)0.42 (0.31, 0.58)<0.001
      C84 (73.7)
      rnC, chemotherapy; O, osimertinib.rn

      Conclusions:
      Time to deterioration of key symptoms was longer and more patients had an improvement in global health status with osimertinib treatment than with chemotherapy, demonstrating improved patient outcomes with osimertinib.

      Clinical trial identification:
      NCT02151981

      Legal entity responsible for the study:
      AstraZeneca

      Funding:
      AstraZeneca

      Disclosure:
      C.K. Lee: Served on advisory boards for AstraZeneca. S. Novello: Served on speaker bureaux for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme Limited and Roche. A. Rydén, H. Mann, S. Ghiorghiu: Employees of AstraZeneca and are AstraZeneca shareholders. A. Templeton, K. Rüdell: Former employees of AstraZeneca and former shareholders. T. Mok: Grant/Research Support from AstraZeneca, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS, Eisai, Taiho; Speaker’s fees with: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, MSD, Novartis, BMS; Major Stock Shareholder in: Sanomics Ltd.; Advisory Board for: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, Clovis Oncology, Merck Serono, MSD, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Inc., Vertex Pharmaceuticals, BMS, geneDecode Co., Ltd., OncoGenex Technologies Inc., Celgene, Ignyta, Inc.; Board of Directors: IASLC, Chinese Lung Cancer Research Foundation Ltd., Chinese Society of Clinical Oncology (CSCO), Hong Kong Cancer Therapy Society (HKCTS).

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      Invited Discussant 85O_PR (ID 528)

      14:45 - 16:15  |  Author(s): E. Smit

      • Abstract
      • Presentation
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      Abstract not provided

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    Immunotherapy for other thoracic tumours (ID 8)

    • Event: ELCC 2017
    • Type: Educational session
    • Track:
    • Presentations: 4
    • +

      Perspectives in SCLC (ID 28)

      09:00 - 10:30  |  Author(s): S. Peters

      • Abstract
      • Slides

      Abstract not provided

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      Realities in mesothelioma (ID 29)

      09:00 - 10:30  |  Author(s): S. Popat

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      Thymic tumours (ID 30)

      09:00 - 10:30  |  Author(s): G. Giaccone

      • Abstract
      • Slides

      Abstract not provided

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      T cell therapies (ID 31)

      09:00 - 10:30  |  Author(s): A. Dingemans

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    Immunotherapy of non-small cell lung cancer (ID 4)

    • Event: ELCC 2017
    • Type: Educational session
    • Track:
    • Presentations: 4
    • +

      First-line treatment (ID 12)

      16:30 - 18:00  |  Author(s): M. Reck

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      Biomarkers (ID 13)

      16:30 - 18:00  |  Author(s): K. Kerr

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      Combination approaches (ID 14)

      16:30 - 18:00  |  Author(s): N. Rizvi

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      Toxicites of immuno-checkpoint blockers (ID 15)

      16:30 - 18:00  |  Author(s): J. Soria

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    ESMO-IASLC Best Abstracts (ID 61)

    • Event: ELCC 2018
    • Type: Best Abstract session
    • Track:
    • Presentations: 7
    • +

      91O - Adjuvant chemotherapy candidates in stage I lung adenocarcinomas following complete lobectomy: What does an analysis based on recurrence risk stratification tell us? (ID 435)

      16:45 - 18:30  |  Presenting Author(s): J. Qian  |  Author(s): J. Xu, S. Wang, F. Qian, W. Yang, B. Zhang, Y. Zhang, X. Zhang, B. Han

      • Abstract
      • Presentation
      • Slides

      Background:
      The study aimed to (i) develop a recurrence risk-scoring model in stage I lung adenocarcinoma (LAD) after complete lobectormy; (ii) explore the high-risk population that would benefit from adjuvant chemotherapy (ACT).

      Methods:
      A retrospective study was performed on 4606 patients with pathologically confirmed stage I LAD who underwent complete lobectomy at Shanghai Chest Hospital from 2008 to 2014. Patients were categorized into the non-ACT group (n = 3514) and ACT group (n = 1092). The nomogram was developed in the non-ACT group using Cox proportional hazards regression to predict 5-year recurrence-free survival (RFS). The predictive value was compared between the nomogram and the 8[th] edition of TNM system. The population that benefited from ACT was determined by comparing RFS between the non-ACT and the ACT group as stratified by the TNM stage, risk score quartiles and 5-year recurrence probability, respectively. The optimal cut-off scores were determined using X-tile software.

      Results:
      Six independent predictors including age, gender, tumor size, pathological subtype, visceral pleural invasion (VPI), and lymphovascular invasion (LVI) were associated with recurrence. The nomogram showed a better accuracy in predicting RFS than the TNM staging [C-index: 0.784 (95% CI: 0.756–0.812) vs 0.719 (95% CI: 0.689–0.749), P = 0.0017]. A trend in ACT benefit was observed along with the increasing risk scores. An improved RFS was exhibited after ACT for patients having a 50% recurrence probability (P = 0.0286). The optimal cut-off of the risk score was set at 203 and 244. ACT was detrimental in patients with risk scores below 203 (P < 0.0001) and beneficial in those with risk scores above 245 (P = 0.0416). Patients with score ≥ 245 accounted for 0.4% of stage IA patients and 7.5% of stage IB patients, respectively. In stage IB, patients with predominant solid/micropapillary subtype (62.8%) was the subgroup with the most percentage of score ≥ 245.

      Conclusions:
      The nomogram provided a more accurate RFS prediction for lobectomized stage I LAD. High-risk population, determined as recurrence risk score ≥ 245, may benefit from postoperative ACT.

      Clinical trial identification:


      Legal entity responsible for the study:
      Shanghai Chest Hospital, Shanghai Jiao Tong University, China

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.

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      109O - Health-related quality of life (QoL) after prophylactic cranial irradiation (PCI) vs no PCI for stage III NSCLC patients: Results from the NVALT-11/DLCRG-02 study (ID 273)

      16:45 - 18:30  |  Presenting Author(s): W. Witlox  |  Author(s): B. Ramaekers, H. Groen, A. Dingemans, J. Praag, J. Belderbos, V. Van Der Noort, H. Van Tinteren, M. Joore, D. De Ruysscher

      • Abstract
      • Presentation
      • Slides

      Background:
      The NVALT-11/DLCRG-02 randomized phase III study compared PCI to observation after chemo-radiotherapy for stage III NSCLC and showed a significant decrease in time to develop symptomatic brain metastases in the PCI arm at the expense of more low-grade mostly neurological toxicity (HR 0.25 95% CI 0.11–0.58). We here report on the QoL.

      Methods:
      EORTC QLQ-C30 and EuroQol 5D (EQ-5D) data measured before PCI and 3, 12, and 24 months thereafter were compared for both arms. Specifically, functional scales and global health status scores (QLQ-C30) as well as VAS and utility scores (EQ-5D) were analysed using non-parametric tests.

      Results:
      In total, 86 and 88 patients were included in the PCI and observational arm respectively, accumulating to 853 observations (five observations completely missing). Baseline QoL was similar between both arms, except for emotional (p = 0.025) and cognitive functioning (p = 0.039) which showed a significantly better score in the PCI arm. At three months, the observational arm scored significantly better on the EQ-VAS (median 70 vs 60, p = 0.017), while EQ-5D utility scores (Dutch tariff) were similar. At three months, QLQ-C30 showed that physical functioning, cognitive functioning, and global disease specific QoL were significantly better in the observational arm (median 83 vs 73, p = 0.003, median 100 vs 83, p = 0.006 and median 67 vs 67, p = 0.017). At later time-points, except for significantly better cognitive functioning at 24 months in the observational arm (median 83 vs 67, p = 0.017), no significantly different QoL (either QLQ-C30 or EQ-5D) was observed between the two arms.Table:Median scores of functional scales and global health status scores of QLQ-C30 and VAS and utility scores of EQ-5D

      Median (PCI)Median (Observation)
      T0T3T12T24T0T3T12T24
      QLQ-C30
      Physical7773878080838077
      Role6767676767676767
      Emotional8383839275888388
      Cognitive100838367831008383
      Social83831008383838392
      Global QoL6767676767676767
      EQ-5D
      Utility score0.8430.7750.8050.8430.8110.8110.7750.843
      VAS score6560707570706970


      Conclusions:
      In conclusion, despite substantially reducing the incidence of brain metastases in NSCLC patients, PCI impairs short term generic QoL as well as disease specific QoL. The impact on long term QoL is limited to problems concerning cognitive functioning only.

      Clinical trial identification:


      Legal entity responsible for the study:
      Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (NVALT)

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.

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      233O - Time to deterioration of symptoms with durvalumab in stage III, locally advanced, unresectable NSCLC: Post-hoc analysis of PACIFIC patient-reported outcomes (ID 703)

      16:45 - 18:30  |  Presenting Author(s): S. Antonia  |  Author(s): R. Hui, M. Özgüroğlu, A. Villegas, D. Daniel, D. Vicente Baz, S. Murakami, A. Rydén, Y. Zhang, P. Dennis

      • Abstract
      • Presentation
      • Slides

      Background:
      Along with improving efficacy outcomes such as progression-free survival (PFS) after concurrent chemoradiotherapy (cCRT) in locally advanced, unresectable NSCLC, it is critical that new therapies are well tolerated in the curative intent setting. We studied the impact of 12 mo of durvalumab on disease symptoms in this setting using patient-reported outcomes (PROs). In a post-hoc analysis of time to deterioration, we adjusted for transient symptom changes by requiring two consecutive deterioration recordings.

      Methods:
      Patients whose disease did not progress after ≥2 cycles of platinum-based cCRT were randomised 2:1 1–42 days post-cCRT to durvalumab 10 mg/kg i.v. or placebo every 2 weeks for up to 12 mo/progression. Co-primary endpoints were PFS and overall survival. PROs were assessed using EORTC QLQ-C30 v3 and QLQ-LC13. Time to deterioration was defined as time from randomisation until the first clinically relevant deterioration (≥10 point change); in the post-hoc analysis, deterioration confirmation was required at the next time point. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using a stratified Cox proportional-hazards model.

      Results:
      In the pre-specified analysis, there was no difference between treatment arms in time to deterioration besides other pain, which favoured durvalumab vs placebo (HR 0.72; 95% CI 0.58–0.89). Our post-hoc analysis indicated notable delays in deterioration of overall pain (HR 0.75; 95% CI 0.60–0.93), chest pain (HR 0.74; 95% CI 0.57–0.97), arm/shoulder pain (HR 0.74; 95% CI 0.58–0.95), nausea/vomiting (HR 0.72; 95% CI 0.54–0.97), insomnia (HR 0.75; 95% CI 0.58–0.97) and haemoptysis (HR 0.70; 95% CI 0.50–0.99) in favour of durvalumab, with no between-group differences for other items.

      Conclusions:
      PACIFIC primary analysis showed that durvalumab significantly improved PFS vs placebo (16.8 mo vs 5.6 mo, respectively) in the post-cCRT setting, and was well tolerated, largely without PRO deterioration. Our post-hoc analysis indicates a delay in several PROs with durvalumab not observed in the pre-specified analysis. Confirmation of worsening may provide a more precise picture of deterioration than one time point alone.

      Clinical trial identification:
      NCT02125461 (April 25, 2014)

      Legal entity responsible for the study:
      AstraZeneca PLC

      Funding:
      AstraZeneca

      Disclosure:
      R. Hui: Personal fees from the following: AstraZeneca, Merck Sharp and Dohme: Advisory Board Member and Speaker Honorarium; Novartis, Pfizer: Advisory Board Member; BMS, Boehringer Ingelheim: Speaker Honorarium. A. Villegas: Celgene, Alexion, BMS: Speaker's Bureau. A. Ryden, Y. Zhang, P. Dennis: AstraZeneca: full-time employment and stock ownership. S. Antonia: Moffitt Cancer Center: Full-time employment, Grants/research support; Novartis: Grants/research support, Advisory board, Honorarium recipient; BMS, Merck, Boehringer Ingelheim, AstraZeneca, Memgen: Advisory board, Honorarium recipient; CBMG: Advisory board, Stock/shareholder, Honorarium recipient. All other authors have declared no conflicts of interest.

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      Invited Discussant 91O, 109O and 233O (ID 682)

      16:45 - 18:30  |  Presenting Author(s): N. Reguart

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      128O - Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with untreated EGFRm advanced NSCLC: FLAURA post-progression outcomes (ID 570)

      16:45 - 18:30  |  Presenting Author(s): D. Planchard  |  Author(s): M. Boyer, J. Lee, A. Dechaphunkul, P. Cheema, T. Takahashi, A. Todd, A. McKeown, Y. Rukazenkov, Y. Ohe

      • Abstract
      • Presentation
      • Slides

      Background:
      In the FLAURA phase 3 study, the third-generation EGFR-TKI osimertinib significantly improved progression-free survival (PFS) vs SoC EGFR-TKIs (gefitinib or erlotinib) in pts with previously untreated Ex19del/L858R (EGFRm) advanced NSCLC (hazard ratio [HR] 0.46 [95% CI 0.37, 0.57]; p < 0.001). Interim overall survival (OS) data was encouraging but not formally statistically significant (HR 0.63 [95% CI 0.45, 0.88]; p = 0.007). Here we report exploratory post-progression outcomes.

      Methods:
      Pts were randomised 1:1 to receive osimertinib (80 mg orally [PO], once daily [QD]) or SoC (gefitinib 250 mg PO QD or erlotinib 150 mg PO QD). Treatment beyond disease progression was allowed if the investigator judged continued clinical benefit; investigators determined subsequent therapy. Pts receiving SoC could cross over to osimertinib after objective disease progression with documented post-progression T790M-positive mutation status.

      Results:
      At data cutoff, 12 June 2017, 138/279 (49%) and 213/277 (77%) pts discontinued osimertinib and SoC, respectively; 82 (29%) and 129 (47%) received a subsequent treatment: EGFR-TKI-containing, 29 (10%) and 97 (35%; 55 [20%] osimertinib); platinum chemotherapy-containing, 46 (16%) and 27 (10%). Median time (mths) to discontinuation of study treatment or death: osimertinib 20.8 (95% CI 17.2, 24.1) vs SoC 11.5 (10.3, 12.8). Median time (mths) to discontinuation of any EGFR-TKI (study treatment and subsequent EGFR-TKI, not interrupted by non-EGFR-TKI therapy) or death: osimertinib 23.0 (19.5, not calculable [NC]) vs SoC 16.0 (14.8, 18.6). Time-to-event post-progression endpoints all favoured osimertinib (Table).

      Osimertinib(n = 279)SoC (n = 277)
      Disease progression or death, n (%)136 (49)206 (74)
      Remained on study treatment for at least 7 days post investigator assessed progression, n/N (%)91/136 (67)145/206 (70)
      Median duration on study treatment post-progression (95% CI), wks[a]8.1 (6.3, 12.3)7.0 (5.9, 8.1)
      TFST
      Pts who started FST or died, n (%)115 (41)175 (63)
      Started FST, n (%)82 (29)129 (47)
      Died, n (%)33 (12)46 (17)
      Median TFST or death (95% CI), mths[a]23.5 (22.0, NC)13.8 (12.3, 15.7)
      HR (95% CI)[b]0.51 (0.40, 0.64), p < 0.0001
      PFS2 (investigator assessed)
      Second progression or death, n (%)73 (26)106 (38)
      Median PFS2 (95% CI), mths[a]NC (23.7, NC)20.0 (18.2, NC)
      HR (95% CI)[b]0.58 (0.44, 0.78), p = 0.0004
      TSST
      Pts who started SST or died, n (%)74 (27)110 (40)
      Started SST, n (%)24 (9)39 (14)
      Died, n (%)50 (18)71 (26)
      Median TSST or death (95% CI), mths[a]NC (NC, NC)25.9 (20.0, NC)
      HR (95% CI)[b]0.60 (0.45, 0.80), p = 0.0005
      aCalculated using the Kaplan-Meier method.bHR and CI were obtained directly from the U and V statistics. The analysis was performed using a log rank test stratified by race (Asian versus non-Asian) and mutation type (Ex19del vs L858R). 2-sided p-value. CI, confidence interval; FST, first subsequent therapy (second-line treatment); HR, hazard ratio; NC, not calculable; PFS2, second progression-free survival (or death) post initiation of second-line treatment (i.e. time from randomisation to second progression on subsequent treatment); TFST, time to first subsequent therapy or death; TSST, time to second subsequent therapy or death; SST, second subsequent therapy; RECIST, Response Evaluation Criteria In Solid Tumors version 1.1.

      Conclusions:
      PFS benefit with osimertinib was preserved throughout time-to-event post-progression endpoints. Step-wise increase of the statistically significant HRs (PFS 0.46, TFST 0.51, PFS2 0.58, TSST 0.60) provides confidence in the interim OS data.

      Clinical trial identification:
      ClinicalTrials.gov NCT02296125

      Legal entity responsible for the study:
      AstraZeneca

      Funding:
      AstraZeneca

      Disclosure:
      D. Planchard: Advisory boards: Astrazeneca, Boehringer, BMS, Pfizer, Novartis, MSD, Roche M. Boyer: Research funding and/or honoraria for advisory board work or talks, paid to my institution, from: AstraZeneca, Roche, Merck Sharpe and Dohme, Pfizer, Amgen, Bristol-Myers Squibb. P. Cheema: Advisory board/Honorarium: AstraZeneca Research grant: AstraZeneca T. Takahashi: Honoraria: AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, Ono Pharmaceutical, Grants: AstraZeneca KK, Pfizer Japan Inc., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K. A. Todd: Employee of AstraZeneca but own no stocks or shares, and am not a member of any board. I am not aware of any other conflicts of interest or opportunities for financial gain. A. McKeown: Employee of, and shareholder in, AstraZeneca. Y. Rukazenkov: Employee of and shareholder in AstraZeneca. Y. Ohe: Grants and personal fees from AstraZeneca, during the conduct of the study; grants and personal fees from AstraZeneca, grants and personal fees from Ono, grants and personal fees from BMS, grants and personal fees from Chougai, grants and personal fees from Pfizer, grants and personal fees from MSD, grants and personal fees from Novartis, grants from Kyorin, grants from Dainippon- Sumitomo, personal fees from Daiichi-Sankyo, personal fees from Nipponkayaku, personal fees from Boehringer Ingelheim, personal fees from Bayer, grants and personal fees from Lilly, outside the submitted work. All personal fees were honoraria for consulting or lectures. All other authors have declared no conflicts of interest.

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      129O - EGFR-TKIs plus local therapy demonstrated survival benefit than TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases (ID 166)

      16:45 - 18:30  |  Presenting Author(s): T. Jiang  |  Author(s): C. Zhou

      • Abstract
      • Slides

      Background:
      Our previous study demonstrated that liver metastases (LM) were the negative predictive and prognostic factor in EGFR-mutant NSCLC patients (Pts) treated with EGFR-TKIs, suggesting that additional treatment is warranted. Recently, several studies reported that local therapy could significantly improve progression-free survival (PFS) in NSCLC Pts with oligometastatic or oligoprogressive disease. This study aimed to investigate whether addition of local therapy to EGFR-TKIs could provide survival benefit in EGFR-mutant NSCLC Pts with oligometastatic or oligoprogressive LM.

      Methods:
      Pts with EGFR-mutant NSCLC and LM were included. Oligometastatic LM was defined as <5 sites in liver without extrahepatic metastases at initial diagnosis. Oligoprogressive LM was defined as <5 sites in liver without extrahepatic metastases during TKIs therapy. For oligoprogressive cohort, PFS1 was calculated from time of initiation of TKI therapy to first RECIST 1.1 defined progress disease (PD) or death. PFS2 was calculated from time of initiation of TKI therapy to off-TKI PD.

      Results:
      289 Pts with LM were enrolled (55 with oligometastatic LM and 63 with oligoprogressive LM). In oligometastatic cohort, 18 Pts received EGFR-TKIs (E) and 21 Pts received TKIs plus local therapy (E + LT) as first-line treatment. Median PFS was significantly longer in E + LT group than in E group (12.2 vs. 7.9 m, P = 0.030). Median OS was numerically longer in E + LT group than in E group (31.7 vs. 21.3 m, P = 0.102). In oligoprogressive cohort, 19 Pts received continuation of TKIs plus local therapy (cE + LT) and 22 Pts received switch therapy (ST). Median PFS1 was comparable. Median PFS2 was dramatically longer in cE + LT group than in ST group (13.9 vs. 8.8 m, P = 0.050). Median OS was marginally significantly longer in cE + LT group than in ST group (24.7 vs. 15.7 m, P = 0.085). Multivariate analysis revealed that addition of local therapy was independently associated with prolonged PFS and OS in Pts with oligometastatic LM.

      Conclusions:
      The current study indicated that EGFR-TKIs plus local therapy demonstrated the prolonged survival benefit than TKIs alone in EGFR-mutant NSCLC Pts with oligometastatic or oligoprogressive LM.

      Clinical trial identification:


      Legal entity responsible for the study:
      Shanghai Pulmonary Hospital

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.

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      Invited Discussant 128O and 129O (ID 683)

      16:45 - 18:30  |  Presenting Author(s): T. Mitsudomi

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      Abstract not provided

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    First line for non-oncogene addicted lung cancer (ID 4)

    • Event: ELCC 2018
    • Type: Educational session
    • Track:
    • Presentations: 4
    • +

      First-line chemotherapy in NSCLC: Where do we stand? (ID 12)

      16:30 - 18:00  |  Presenting Author(s): R.A. Stahel

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      Abstract not provided

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      Immunotherapy in the first-line setting: What have we achieved? (ID 13)

      16:30 - 18:00  |  Presenting Author(s): M. Reck

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      Abstract not provided

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      First-line therapy in PS2 and elderly patients: Any new signals? (ID 14)

      16:30 - 18:00  |  Presenting Author(s): E. Quoix

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      Abstract not provided

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      First-line therapy: What might we expect for the future? (ID 15)

      16:30 - 18:00  |  Presenting Author(s): G. Scagliotti

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      Abstract not provided

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    First line for oncogene addicted lung cancer (ID 2)

    • Event: ELCC 2018
    • Type: Educational session
    • Track:
    • Presentations: 4
    • +

      Is PFS still a relevant endpoint for first-line TKIs? (ID 2)

      14:30 - 16:00  |  Presenting Author(s): S. Ramalingam

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      • Presentation
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      Abstract not provided

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      First vs second vs third generation EGFR TKI (ID 3)

      14:30 - 16:00  |  Presenting Author(s): J. Wolf

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      Abstract not provided

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      Key factors that determine the selection of first-line ALK inhibtiors (ID 4)

      14:30 - 16:00  |  Presenting Author(s): F. Blackhall

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      Abstract not provided

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      The role of first-line combination therapy for oncogene addicted lung cancer (ID 5)

      14:30 - 16:00  |  Presenting Author(s): T. Seto

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      • Presentation
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      Abstract not provided

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    HHH Award Keynote Lecture (ID 1)

    • Event: ELCC 2018
    • Type: Keynote Lecture
    • Track:
    • Presentations: 1
    • +

      The power of the multiple H (ID 1)

      13:45 - 14:15  |  Presenting Author(s): F. Barlesi

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      Abstract not provided

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    Immunotherapy combinations (ID 21)

    • Event: ELCC 2018
    • Type: Educational session
    • Track:
    • Presentations: 4
    • +

      Immunotherapy and chemotherapy combinations (ID 84)

      09:00 - 10:30  |  Presenting Author(s): S. Ponce Aix

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      Abstract not provided

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      Combination of immunotherapy with targeted therapies (ID 85)

      09:00 - 10:30  |  Presenting Author(s): L. Hendriks

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      Abstract not provided

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      Combination of immunotherapies (ID 86)

      09:00 - 10:30  |  Presenting Author(s): S. Antonia

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      Abstract not provided

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      Combination of immunotherapy with radiation therapy (ID 87)

      09:00 - 10:30  |  Presenting Author(s): H. Choy

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      Abstract not provided

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