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R. Pirker

Moderator of

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    PL02a - Distinguished Lecture (ID 480)

    • Event: WCLC 2016
    • Type: Plenary
    • Track:
    • Presentations: 1
    • Now Available
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      Welcome Address (Now Available) (ID 7160)

      H. Fischer

      • Abstract
      • Presentation

      Abstract not provided

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    PL03 - Presidential Symposium (ID 428)

    • Event: WCLC 2016
    • Type: Plenary
    • Track:
    • Presentations: 10
    • Now Available
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      PL03.01 - Presidential Address (Now Available) (ID 6881)

      D.P. Carbone

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PL03.02 - Lung Cancer Staging – Changing the Clinical Practice (Now Available) (ID 6866)

      R. Rami-Porta

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Introduction At the time of the 17[th] World Conference on Lung Cancer, the 8[th] edition of the tumor, node and metastasis (TNM) classification of lung cancer will have been published by the Union for International Cancer Control, the American Joint Committee on Cancer and the International Association for the Study of Lung Cancer (IASLC) in their respective staging manuals. The innovations introduced, based on the analyses of the new IASLC database that includes 70,967 evaluable patients with non-small cell lung cancer and 6,189 with small cell lung cancer are described in the table. (1-9) These innovations will lead to some changes in clinical practice that are worth reflecting on. Table. Innovations introduced in the 8[th] edition of the TNM classification of lung cancer.

      Descriptor 8[th] edition
      T component
      >/= 1cm T1a
      >1 – 2cm T1b
      >2 – 3cm T1c
      >3 – 4cm T2a
      >4 – 5cm T2b
      >5 – 7cm T3
      >7cm T4
      Brochus <2cm from carina T2
      Total atelectasis/pneumonitis T2
      Diaphragm inasion T4
      Mediastinal pleura invasion -
      M component
      Metastases in thoracic cavity M1a
      Single extrathoracic metastasis M1b
      Multiple extrathoracic metastases M1c
      Other innovations in classification
      Second primaries One TNM for each
      Separate tumor nodules T3, T4 and M1a
      Multifocal adenocarcinomas with ground glass opacity/lepidic features Highest T (#/m) and global N and M
      Pneumonic type adenocarcinoma T3, T4 and M1a
      The T component Tumor size is a much more relevant prognostic factor than in previous editions and is now a descriptor in all T categories. Therefore, tumor size measurement should be carefully performed because small changes in size mean important changes in prognosis. (2) In part-solid tumors, only the solid/invasive part counts to measure tumor size. (7) The fact that adenocarcinoma in situ –Tis(AIS) – and minimally invasive adenocarcinoma –T1mi– have their own coding in the TNM classification will increase their awareness. (7) These, together with the smallest coded solid tumors, those of one cm or less in largest dimension –T1a– can become the base from which to study therapeutic options, such as sublobar resections, stereotactic radiotherapy, radiofrequency ablation; tumor biology, including tumor growth, tumor density and intensity of the standardized uptake value, as well as molecular profile and genetic signatures. Visceral pleural invasion and its two categories (PL1: invasion beyond its elastic layer; and PL2: invasion of the pleural surface) have been confirmed as important prognostic factors. (2) This means that pathologists should intensively investigate the identification of visceral pleural invasion, and, if it is not evident by the standard hematoxylin and eosine stains, elastic stains should be used, as recommended in the 7[th] edition of the TNM classification. (10) The N component Although there will be no changes in the N categories, the analyses for the 8[th] edition have shown that quantification of nodal disease has prognostic implications. This had already been evident in the 7[th] edition, when it was found that the number of involved nodal zones was prognostic. The analyses for the 8[th] edition have considered the number of involved nodal stations and have found that the more nodal stations involved, the worse the prognosis; and that the prognosis of tumors with involvement of multiple N1 stations was similar to that of tumors with single station N2 without concomitant N1 disease (skip metastases). (3) The findings of the 7[th] edition already raised the issue of indicating upfront resection in patients with tumors with single N2 zone involvement, because their prognosis was the same as that of tumors with multiple N1 zones. The question will be raised again in the light of the results of the 8[th] edition. However, in both occasions, the quantification of nodal disease derived from pathological staging of those tumors that had been resected and the resection had been accompanied by a properly performed systematic nodal dissection. This is difficult to replicate at clinical staging, the moment at which therapeutic decisions are made, unless a transcervical mediastinoscopic lymphadenectomy is performed. This lymphadenectomy has been found to be equivalent to that performed at the time of resection, either by thoracoscopic or open surgery, and is the only pre-resection test that can define single station or single zone N2 disease reliably. The M component There is no change in the metastasis within the thoracic cavity (M1a), but single extrathoracic metastases have better prognosis than multiple extrathoracic metastasis in one or in several organs, and different categories have been defined for them: M1b for single and M1c for multiple extrathoracic metastases. (4) The fact that single extrathoracic metastasis have their own category will facilitate the redefinition of oligometastatic and oligoprogressive disease, the establishment of therapeutic protocols with radical intention, and the investigation of all therapeutic modalities to eliminate the advance disease. However, clinical staging will have to be precise and will have to determine the number and the organ location of the metastatic deposits. The stages Some TNM subsets have moved from one stage to another and new stages and sub-stages have been created to accommodate groups of tumors with similar prognosis. (5) As it occurred with the 7[th] edition, the question of how to treat patients whose tumors have changed stage will be raised at multidisciplinary team meetings. Taxonomic changes do not necessarily mean an automatic change in therapy if the clinical trials performed to test therapeutic options did not include the tumors that are now included in the selected stages for study. Therefore, in the absence of results from clinical trials, clinical judgment will have to determine what the best options are for a given patient with a given tumor. Lung cancer with multiple lesions The 8[th] edition will provide a set of rules with the intention to classify lung cancers with multiple lesions in a homogeneous way. (8) It is our responsibility to follow the rules to collect prospective data uniformly and validate the given recommendations with international data. Conclusion The 8[th] edition will help us refine prognosis both at clinical and pathologic staging and stratify tumors in future clinical trials, but will require more attention from us at measuring tumor size, at determining nodal disease, at searching for metastases, and at using clinical judgment to indicate treatment. References 1. Rami-Porta R, Bolejack V, Giroux DJ et al. The IASLC lung cancer staging project: the new database to inform the eighth edition of the TNM classification of lung cancer. J Thorac Oncol 2014; 9: 1618-1624. 2. Rami-Porta R, Bolejack V, Crowley J et al. The IASLC lung cancer staging project: proposals for the revisions of the T descriptors in the forthcoming 8[th] edition of the TNM classification for lung cancer. J Thorac Oncol 2015; 10: 990-1003. 3. Asamura H, Chansky K, Crowley J et al. The IASLC Lung Cancer Staging Project: proposals for the revisions of the N descriptors in the forthcoming 8[th] edition of the TNM classification for lung cancer. J Thorac Oncol 2015; 10: 1675-1684. 4. Eberhardt WEE, Mitchell A, Crowley J et al. The IASLC lung cancer staging project: proposals for the revisions of the M descriptors in the forthcoming 8[th] edition of the TNM classification for lung cancer. J Thorac Oncol 2015; 10: 1515-1522. 5. Goldstraw P, Chansky K, Crowley J et al. The IASLC lung cancer staging project: proposals for the revision of the stage grouping in the forthcoming (8th) edition of the TNM classification of lung cancer. J Thorac Oncol 2016; 11: 39-51. 6. Nicholson AG, Chansky K, Crowley J et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: proposals for the revision of the clinical and pathologic staging of small cell lung cancer in the forthcoming eighth edition of the TNM classification for lung cancer. J Thorac Oncol 2016; 11: 300-311. 7. Travis WD, Asamura H, Bankier A et al. The IASLC Lung Cancer Staging Project: proposals for coding T categories for subsolid nodules and assessment of tumor size in part-solid tumors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol 2016; 11: 1204-1223. 8. Detterbeck FC, Nicholson AG, Franklin WA et al. The IASLC Lung Cancer Staging Project: summary of proposals for revisions of the classification of lung cancers with multiple pulmonary sites of involvement in the forthcoming eighth edition of the TNM classification. J Thorac Oncol 2016; 11: 539-650. 9. Detterbeck FC, Chansky K, Groome P et al. The IASLC Lung Cancer Staging Project: methodology and validation used in the development of proposals for revision of the stage classification of NSCLC in the forthcoming (eighth) edition of the TNM classification of lung cancer. J Thorac Oncol 2016; 11: 1433-1446. 10. Travis WD, Brambilla E, Rami-Porta R et al. Visceral pleural invasion: pathologic criteria and use of elastic stains. Proposal for the 7[th] edition of the TNM classification for lung cancer. J Thorac Oncol 2008; 3: 1384-1390.

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      PL03.03 - Randomised Phase III Study of Osimertinib vs Platinum-Pemetrexed for EGFR T790M-Positive Advanced NSCLC (AURA3) (Abstract under Embargo until December 6, 7:00 CET) (Now Available) (ID 4452)

      V. Papadimitrakopoulou, Y.L. Wu, M. Ahn, S.S. Ramalingam, M.C. Garassino, H.R. Kim, F. Shepherd, H. Akamatsu, W.S. Theelen, C.K. Lee, M. Sebastian, A. Templeton, M. Marotti, S. Ghiorghiu, T. Mok

      • Abstract
      • Presentation
      • Slides

      Background:
      Osimertinib is a potent, irreversible, CNS active, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for sensitising (EGFRm) and T790M resistance mutations. Osimertinib is indicated for the treatment of patients with locally advanced or metastatic EGFR T790M-positive NSCLC. AURA3 (NCT02151981) is a Phase III, open-label, randomised study assessing the efficacy and safety of osimertinib versus platinum-based chemotherapy plus pemetrexed in patients with EGFR T790M-positive advanced NSCLC, whose tumours progressed on first-line EGFR-TKI therapy.

      Methods:
      Eligible patients were ≥18 years with documented EGFRm, radiological disease progression following first-line EGFR-TKI and centrally confirmed T790M-positive (by cobas® EGFR Mutation Test) from a tissue biopsy after disease progression. Asymptomatic, stable CNS metastases were allowed. Patients were randomised 2:1 to osimertinib 80 mg orally, once daily or platinum-pemetrexed (pemetrexed 500 mg/m[2] plus either cisplatin 75 mg/m[2] or carboplatin AUC5) every three weeks for up to six cycles; pemetrexed could be continued as maintenance treatment. Primary endpoint was progression-free survival (PFS) by investigator assessment according to RECIST v1.1; sensitivity analysis was by blinded independent central review (BICR).

      Results:
      A total of 419 patients were randomised to treatment (osimertinib, n=279; platinum-pemetrexed, n=140). Baseline characteristics were generally balanced across treatment groups: female 64%, Asian 65%, never smoker 68%, CNS metastases 34%, EGFR exon 19 deletion 66%. Osimertinib significantly improved PFS compared with platinum-pemetrexed: hazard ratio [HR] 0.30; 95% CI: 0.23, 0.41; p<0.001 (median 10.1 months vs 4.4 months). The result was consistent with PFS analysis by BICR: HR 0.28; 95% CI: 0.20, 0.38; p<0.001 (11.0 months vs 4.2 months). Objective response rate was significantly improved with osimertinib (71%) vs platinum-pemetrexed (31%); odds ratio 5.39 (95% CI: 3.47, 8.48; p<0.001). Median duration of response was 9.7 months (95% CI 8.3, 11.6) with osimertinib and 4.1 months (95% CI 3.0, 5.6) with platinum-pemetrexed. Grade ≥3 causally-related adverse events (AEs) as assessed by the investigator were reported in 6% of patients (n=16) treated with osimertinib and 34% (n=46) treated with platinum-pemetrexed. Most common causally-related AEs in the osimertinib group: diarrhoea (29% [grade ≥3, 1%]), rash (28% [<1%]); in the platinum-pemetrexed group: nausea (47% [3%]), decreased appetite (32% [3%]).

      Conclusion:
      In patients with EGFR T790M-positive advanced NSCLC following progression on EGFR-TKI treatment, osimertinib demonstrated a superior clinically-meaningful efficacy over platinum-pemetrexed, with a 70% reduction in the risk of disease progression, and well-characterised safety profile, establishing the new standard of care for these patients.

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      PL03.04 - Discussant for PL03.02, PL03.03 (Now Available) (ID 7156)

      T. Mitsudomi

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PL03.05 - BRAIN: A Phase Ⅲ Trial Comparing WBI and Chemotherapy with Icotinib in NSCLC with Brain Metastases Harboring EGFR Mutations (CTONG 1201) (Abstract under Embargo until December 6, 7:00 CET) (Now Available) (ID 4570)

      Y.L. Wu, J.-. Yang, C. Zhou, J. Feng, S. Lu, Y. Song, C. Huang, G. Wu, Y. Cheng, L. Zhang, C. Hu, G. Chen, L. Zhang, X. Liu, H. Yan, F. Tan, Y. Huang

      • Abstract
      • Presentation
      • Slides

      Background:
      Non-small cell lung cancer (NSCLC) with brain metastases (M) had a poor prognosis. Whole brain irradiation (WBI) is a standard of care for this critical medical condition. The median survival is only 4-6 months. Small molecule inhibitors of epidermal growth factor receptor (EGFR) including icotinib achieved very successful results in advanced NSCLC with EGFR mutations. There were no prospective randomized clinical trials to explore the efficacy of EGFR tyrosine kinase inhibitors (TKIs) on brain M.

      Methods:
      Advanced NSCLC with EGFR sensitive mutations and brain M were randomized to WBI plus chemotherapy (chemo) or icotinib. Patients in WBI arm received radiotherapy with 30Gy/3Gy/10 fractions plus concurrent or sequential doublet chemo of 4-6 cycles. Patients in EGFR TKI arm received icotinib 125mg orally tid until disease progression. Icotinib could be continued beyond progression if clinical benefit was observed by the investigator. Crossover to icotinib from WBI could be permitted. Key inclusion criteria were EGFR mutations and radiologically confirmed brain M with at least 3 lesions. The primary endpoint was intracranial progression-free survival (iPFS) by investigator assessments according to RECIST v1.1. The secondary endpoints included objective response rate (ORR), PFS and overall survival (OS). Safety and tolerability were assessed by measuring adverse events (AEs) (CTCAE v4).

      Results:
      From Dec. 2012 to June 2015, 176 patients from 17 sites were randomized to WBI+Chemo arm (N=91) or icotinib arm (N=85). The baseline clinicopathologic factors were balanced between the two groups. Median age was 58, PS 1 was 87.2%, non-smoker 70.9%, adenocarcinoma 96.8%, symptomatic brain M were 16.5%. Icotinib significantly improved median iPFS compared with WBI+chemo: hazard ratio [HR] 0.56; 95% CI: 0.36-0.90; p=0.014 (10.0 vs 4.8 months). Median PFS was 6.8 vs 3.4 months, (HR 0.44, 95% CI 0.31-0.63, P<0.001). Median OS had no significant difference between the arms (18.0 vs 20.5 months, HR 0.93, 95%CI 0.60-1.44, P=0.734). Intracranial ORR was significantly improved with icotinib than WBI+Chemo (67.1% vs 40.9%; p<0.001); Overall ORR was 55.0% vs 11.1% (P<0.001). Grade ≥3 AEs assessed by the investigators were reported in 8.2% (N=7) of patients treated with icotinib and 26.2% (N=28) treated with WBI+Chemo. Most common causally related AEs in the icotinib arm were increased liver transaminase & rash; in the WBI+Chemo arm were hematologic toxicity.

      Conclusion:
      Icotinib demonstrated superior iPFS, PFS and ORR over WBI+Chemo in EGFR mutant advanced NSCLC with brain M, and well-tolerated safety profile. Icotinib would be a treatment option for EGFR mutant patients with brain M (NCT01724801).

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      PL03.06 - Discussant for PL03.05 (Now Available) (ID 7154)

      J. Jassem

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PL03.07 - First-line Ceritinib Versus Chemotherapy in Patients With ALK-rearranged (ALK+) NSCLC: A Randomized, Phase 3 Study (ASCEND-4) (Abstract under Embargo until December 6, 7:00 CET) (Now Available) (ID 4987)

      G. De Castro Jr, D.S. Tan, L. Crinò, Y.L. Wu, L. Paz-Ares, J. Wolf, S.L. Geater, S. Orlov, D. Cortinovis, C. Yu, M.J. Hochmair, A.B. Cortot, C. Tsai, D. Moro-Sibilot, R. García Campelo, F. Branle, P. Sen, T. McCulloch, J. Soria

      • Abstract
      • Presentation
      • Slides

      Background:
      Here, we report results of ceritinib versus chemotherapy as first-line treatment for advanced ALK+ NSCLC.

      Methods:
      Untreated ALK+ (IHC confirmed), advanced, nonsquamous NSCLC patients (N=376; median age, 54 years) were randomized (1:1) to ceritinib 750 mg/day (n=189 [59 with brain metastases (BM)]) or chemotherapy (n=187 [62 with BM]; [pemetrexed 500 mg/m[2] plus cisplatin 75 mg/m[2] or carboplatin AUC 5-6] for 4 cycles followed by maintenance pemetrexed), stratified by WHO PS (0 vs 1-2), BM at screening, and prior neo-/adjuvant chemotherapy. Crossover from chemotherapy to ceritinib was allowed at progression (n=80 crossed-over).

      Results:
      Median treatment exposure was 66.4 weeks for ceritinib and 26.9 weeks for chemotherapy. Median follow-up duration was 19.7 months (randomization to cut-off date). The study met its primary objective, with ceritinib demonstrating statistically significant improvement in BIRC PFS (RECIST 1.1; median, 16.6 [12.6, 27.2] vs 8.1 months [5.8, 11.1], HR=0.55, P<0.001) versus chemotherapy. OS was immature (HR, 0.73 [0.50, 1.08]; P=0.056) with 42.3% of required events at interim analysis. ORR (BIRC, 72.5% vs 26.7%) and DOR (BIRC, median, 23.9 vs 11.1 months) were also higher with ceritinib versus chemotherapy. Among patients with measurable baseline BM and ≥1 postbaseline assessment, intracranial ORR (BIRC neuroradiologist; modified RECIST v1.1) was higher with ceritinib (72.7% [49.8, 89.3] vs 27.3% [10.7, 50.2]) versus chemotherapy (Table). Most common AEs (>50%) with ceritinib were diarrhea (84.7%), nausea (68.8%), vomiting (66.1%), ALT increase (60.3%), and AST increase (52.9%). Overall, 5.3% ceritinib- and 11.4% chemotherapy-treated patients discontinued due to AEs suspected to be drug-related. Figure 1



      Conclusion:
      First-line ceritinib achieved statistically significant and clinically meaningful improvement in median PFS with an estimated 45% risk reduction in advanced ALK+ NSCLC versus chemotherapy including maintenance. Moreover, ceritinib achieved high and durable systemic responses and high OIRR in patients with measurable BM. Safety profile of ceritinib is consistent with previously reported.

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      PL03.08 - Discussant for PL03.07 (Now Available) (ID 7155)

      F. Blackhall

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PL03.09 - Phase 3 Study of Ganetespib, a Heat Shock Protein 90 Inhibitor, with Docetaxel versus Docetaxel in Advanced Non-Small Cell Lung Cancer (GALAXY-2) (Abstract under Embargo until December 6, 7:00 CET) (Now Available) (ID 5232)

      R.N. Pillai, D.A. Fennell, V. Kovcin, T.E. Ciuleanu, R. Ramlau, D. Kowalski, M. Schenker, B. Perin, I. Yalcin, F. Teofilovici, V.M. Vukovic, S.S. Ramalingam

      • Abstract
      • Presentation
      • Slides

      Background:
      Heat shock protein 90 functions as a chaperone to stabilize oncoproteins. Ganetespib (G), a highly potent Hsp90 inhibitor, has demonstrated efficacy in combination with docetaxel (D) over D alone in the second-line therapy of patients with advanced adenocarcinoma of the lung in a phase 2 study.

      Methods:
      GALAXY-2 is a randomized (1:1), international, open-label study of D with or without G. Patients with advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC) of adenocarcinoma histology, EGFR and ALK wild-type, diagnosed ≥ 6 months prior to study entry, one prior systemic therapy and ECOG PS 0-1 were eligible. D was given at 75 mg/m[2] on day 1 of three-week cycle; D was given on day 1 with G at 150 mg/m[2 ]on Days 1 and 15 of each cycle. Patients were stratified by performance status (PS), LDH, and geographic region. Primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and OS in elevated LDH (eLDH) patients. We report the results of a planned interim analysis at 336 events, which occurred on October 5, 2015, with type I error level set at 0.01 (2 sided stratified log-rank test).

      Results:
      677 patients were randomized with 335 patients in G+D arm and 337 patients in D arm. Baseline characteristics: females 60%, age < 65 68%; never-smoker 18%; PS 0 36%; eLDH 29%; North America/Western Europe 39%. The median number of cycles delivered was 5 in G+D and 4 in D arm. There was no difference in median OS (mOS) for the two arms: 10.9 months with G+D versus 10.5 months with D alone. The hazard ratio for OS was 1.111 (95% CI 0.899-1.372), which met the early stopping criteria for futility. Median PFS was similar in the two arms: 4.2 versus 4.3 months, G+D and D, respectively (HR 1.161, 95% CI 0.961-1.403). There was no improvement with the addition of G for any secondary endpoint, including survival in the eLDH and EGFR and ALK negative populations, response rate, or progression due to new metastatic lesions. The most common grade 3/4 treatment-emergent adverse event in both arms was neutropenia (31.1% versus 24.3%, G+D and D, respectively).

      Conclusion:
      The addition of ganetespib to docetaxel did not result in improved efficacy for salvage therapy of patients with advanced stage lung adenocarcinoma.

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      PL03.10 - Discussant for PL03.09 (ID 7157)

      D.R. Gandara

      • Abstract
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      Abstract not provided

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    PL04b - Plenary Keynote Lecture (ID 489)

    • Event: WCLC 2016
    • Type: Plenary
    • Track:
    • Presentations: 1
    • Now Available
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      PL04b.01 - The Role of Doctors in a Globalized World (Now Available) (ID 6896)

      • Abstract
      • Presentation

      Abstract not provided

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    PR01 - Press Conference (ID 495)

    • Event: WCLC 2016
    • Type: Press Conference
    • Track:
    • Presentations: 6
    • Now Available
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      PR01.01 - Welcome (ID 7198)

      R. Pirker, G.V. Scagliotti

      • Abstract

      Abstract not provided

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      PR01.02 - Shared Decision Making (SDM) and Patient Decision Aids (PDAs) in Lung Cancer: Survey of Patients, Significant Others or Caregivers (Now Available) (ID 7199)

      L. Gaspar

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PR01.03 - The ALCF Centers of Excellence Model Delivers a Standard of Care to the Community Similar to Academic and Research Centers (Now Available) (ID 7200)

      R.U. Osarogiagbon

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PR01.04 - Mesothelioma Workshop (Now Available) (ID 7201)

      M. Carbone

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PR01.05 - E-health and Future Technologies in Evidence Based Nursing Care (ID 7202)

      R. Maguire

      • Abstract
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      Abstract not provided

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      PR01.06 - Honored Guest (ID 7203)

      • Abstract

      Abstract not provided



Author of

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    P2.02 - Poster Session with Presenters Present (ID 462)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      P2.02-011 - Management of Non-Small-Cell Lung Cancer (NSCLC) Stage III Patients in Central European Countries (ID 4608)

      R. Pirker

      • Abstract

      Background:
      The aim of the study is to determine the actual standard management of patients with stage III NSCLC in Central European centres/countries. The project is a multicentre, prospective, non-interventional registry.

      Methods:
      After ethical committee approval and signed informed consent, the data about diagnostic and therapeutic procedures of consecutive patients diagnosed with stage III NSCLC (UICC7) were collected in web-based registry organised by the IBA MUNI, Brno, Czech Republic.

      Results:
      With cut-off 30 June 2016, 509 patients from 7 countries/16 centres were enrolled, median number of patients per centre being 23 (range 6-99). There were 163 (32%) women and 37 (7%) never smokers. Performance status distribution was as follows: ECOG 0, 1, 2 and 3 in 29%, 56%, 12% and 3%, respectively. Squamous cancer was found in 52%, adenocarcinoma in 39%, not otherwise specified in 5% and others in 4% of cases. Genetic mutations were examined in 119 (23%) patients, predominantly EGFR in 111 subjects with 10 (8%) positive findings, while the ALK mutation in 64 patients with no positive finding. Regular staging procedures were X-Ray scan (97%), chest CT (96%) and bronchoscopy (89%). Staging was completed by abdominal CT in 66% of patients, abdominal US in 29%, PET/CT in 22%, bone scan in 17% and brain CT or MRI in 13%, respectively. Stage IIIA was found in 59% and stage IIIB in 41% of patients. N2/N3 nodes were diagnosed in 60%/22% of patients. Pathological mediastinal lymph-node positivity was confirmed in 109 (21%) patients (6% EBUS, 0.2% VATS, 1% mediastinoscopy, 1% transbronchial biopsy and 13% surgery). Median time from diagnosis to first treatment was 23 days (range 0–321). Treatment procedures were: surgery 138 (27%), chest radiotherapy 246 (48%) and chemotherapy 409 (80%) of subjects, respectively. Chemotherapy as only modality was given in 136 (27%) of patients. Surgery was combined with radiation in 6 cases, with chemotherapy in 79 (16%) cases and with both chemotherapy and radiotherapy in 37 (7%) patients. Chemotherapy plus radiotherapy was given in 159 (31%) patients including concurrent chemoradiotherapy in 67 (13%) cases. At the time of cut-off, 64% patients were alive, median survival time was not reached, and the 1-year estimated survival rate was 71%.

      Conclusion:
      The most prevalent histology was squamous cancer. Histopathological examination of mediastinal lymph-nodes was done in 21% of patients, mostly during surgery. Majority of patients (55%) were treated with combination therapy. Palliative chemotherapy only was given in 27% of patients. Survival data are not mature.

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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-075 - PD-1 Protein Expression Predicts Survival in Resected Adenocarcinomas of the Lung (ID 5641)

      R. Pirker

      • Abstract

      Background:
      Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) have demonstrated clinical activity in patients with advanced non-small cell lung carcinoma (NSCLC). The ability of PD-1 and PD-L1 immunohistochemistry (IHC) to predict benefit of immune checkpoint inhibitors remains controversial. We assessed the prognostic value of PD-1 and PD-L1 IHC in patients with completely resected adenocarcinoma of the lung.

      Methods:
      We determined protein expression of PD-1 and PD-L1 in formalin-fixed paraffin-embedded surgical specimens of 161 NSCLC patients with adenocarcinoma histology by IHC. We used the EH33 antibody (Cell Signaling) for PD-1 and the E1L3N antibody (Cell Signaling) for PD-L1 IHC. Cut-points of ≥1% PD-1-positive immune cells at any staining intensity and ≥1% PD-L1-positive tumor cells at any staining intensity were correlated with clinicopathological features and patient survival.

      Results:
      Positive PD-1 immunostaining in immune cells was observed in 71 of 159 (45%) evaluable tumor samples. PD-1 positive staining was not significantly associated with any of the clinicopathological features. Positive PD-1 immunostaining was associated with longer recurrence-free and overall survival of the patients. Multivariate Cox proportional hazards regression analyses identified PD-1 to be an independent prognostic factor for recurrence (adjusted hazard ratio [HR] for recurrence 0.58; 95% confidence interval [CI] 0.36 to 0.94; P = 0.026) and death (adjusted HR for death 0.46; 95% CI 0.26 to 0.82; P = 0.008). PD-L1 positive staining in tumor cells was seen in 59 of 161 (37%) cases. Positive PD-L1 immunostaining correlated with KRAS mutation (P = 0.019) and type of surgery (P = 0.01) but was not significantly associated with any of the other clinicopathological parameters. Positive PD-L1 immunostaining was not associated with survival of the patients (adjusted HR for recurrence 0.92; 95% CI 0.58 to 1.47; P = 0.733; adjusted HR for death 0.61; 95% CI 0.34 to 1.07; P = 0.084).

      Conclusion:
      Positive PD-1 but not PD-L1 immunostaining is a favorable independent prognostic factor in patients with completely resected adenocarcinoma of the lung.

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    P3.02b - Poster Session with Presenters Present (ID 494)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      P3.02b-032 - Association between EGFR T790M Mutation Copy Numbers in Cell-Free Plasma DNA and Response to Osimertinib in Advanced NSCLC (Now Available) (ID 5454)

      R. Pirker

      • Abstract
      • Slides

      Background:
      Patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC) who developed the T790M resistance mutation during treatment with EGFR tyrosine kinase inhibitors (TKIs) benefit from treatment with third-generation EGFR TKIs such as osimertinib. Treatment with osimertinib requires the confirmation of the presence of the T790M mutation by re-biopsy of the tumor or by analysis of cell-free plasma DNA from blood samples (liquid biopsy). The purpose of our study was to compare T790M mutation copy numbers in cell-free plasma DNA with response to osimertinib.

      Methods:
      From April 2015 to June 2016, we included 44 patients with advanced T790M-positive NSCLC who received osimertinib after previous disease progression with an EFGR TKI and in whom response to osimertinib was evaluable. T790M mutation status was assessed by droplet digital PCR in cell-free plasma DNA. The threshold for T790M positivity was >1 copy/mL.

      Results:
      The T790M mutation status was assessed in all patients by liquid biopsy and in 18 patients also by re-biopsy of the tumor. All 44 patients were T790M-positive in the liquid biopsy. Two out of 18 (11%) patients had a T790M-negative re-biopsy. Thirty-seven patients (86%) showed a response to treatment with osimertinib: 13 (29.5%) complete responses (CR), 24 (54.5%) partial responses (PR), one (2%) stable disease (SD), and six (14%) progressive disease (PD) (Table 1). We observed no statistically significant association between response to osimertinib and T790M copy numbers (p=0.54; Table 1). The median T790M copy numbers across response categories were: CR 25 copies/mL (range 1.7-38092 copies/mL), PR 14 copies/mL (range 1.6-7282 copies/mL), SD+PD 6 copies/mL (range 1.8-475 copies/mL).

      Table 1 Response
      Copies/mL CR PR SD PD
      <10 5 (39%) 11 (46%) 0 (0%) 4 (67%)
      ≥10 8 (62%) 13 (54%) 1 (100%) 2 (33%)


      Conclusion:
      Patients benefited from osimertinib treatment independent of T790M copy numbers in the blood samples. Although limited by low numbers, we observed a trend towards better response to osimertinib in patients with ≥10 T790M copies/mL.

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    PL05 - Closing Plenary Session: A Life in Thoracic Oncology - Reflections from Giants on Milestones in the Treatment Advances in Lung Cancer (ID 433)

    • Event: WCLC 2016
    • Type: Plenary
    • Track:
    • Presentations: 1
    • Now Available
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      PL05.09 - Farewell (Now Available) (ID 6921)

      R. Pirker

      • Abstract
      • Presentation

      Abstract not provided

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    PR01 - Press Conference (ID 495)

    • Event: WCLC 2016
    • Type: Press Conference
    • Track:
    • Presentations: 1
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      PR01.01 - Welcome (ID 7198)

      R. Pirker

      • Abstract

      Abstract not provided

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    SC10 - Squamous Cell NSCLC (ID 334)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      SC10.03 - Anti-EGFR Monoclonal Antibodies in Squamous Cell NSCLC (Now Available) (ID 6639)

      R. Pirker

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Patients with advanced squamous NSCLC receive first-line chemotherapy with a platin-based doublet. Combining first-line chemotherapy with EGFR-directed monoclonal antibodies has been studied as a strategy to improve outcome of these patients. Anti-EGFR monoclonal antibodies inhibit EGFR-mediated signal transduction and may also act via immunological mechanisms. Several monoclonal antibodies have been studied within clinical trials and data from phase III trials are available for cetuximab and necitumumab (for review see ref. 1). Two randomized phase III trials compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced NSCLC (2, 3). The FLEX trial demonstrated improved overall survival for cetuximab added to chemotherapy in patients with advanced NSCLC and enriched for EGFR expression in their tumors (2). The hazard ratio was 0.87 (p=0.044), median survival times were 11.3 months and 10.1 months, and 1-year survival rates were 47% and 42%, respectively. For patients with squamous cell carcinomas (n=347), the hazard ratio was 0.80 and median survival times were 10.2 months and 8.9 months, respectively. The BMS 099 trial failed to show an improvement in progression-free survival for cetuximab added to carboplatin plus paclitaxel in unselected patients with advanced NSCLC (3). A meta-analysis based on individual patient data from four randomized trials demonstrated a survival benefit for chemotherapy plus cetuximab compared to chemotherapy alone (4). The hazard ratio was 0.88 (95% CI 0.79-0.97; p=0.009). The benefit was greater in patients with squamous NSCLC in whom a hazard ratio of 0.77 (95% CI 0.64-0.93) was seen. Necitumumab has also been studied in combination with first-line chemotherapy in two phase III trials (5, 6). The SQUIRE trial assessed cisplatin plus gemcitabine with or without necitumumab in 1,093 patients with advanced squamous NSCLC (5). Necitumumab was intravenously administered at a dose of 800 mg on days 1 and 8 of every 21 days and was planned to be continued after the end of chemotherapy until disease progression or intolerable toxicity. Necitumumab improved the outcome of chemotherapy. The hazard ratio was 0.84 (95% CI 0.74-0.96; p=0.012). Median survival times were 11.5 months and 9.9 months, and 1-year survival rates were 47.7% and 42.8% for the chemotherapy-plus-necitumab arm and chemotherapy arm, respectively. Progression-free survival and response rates were also improved with the combined treatment. Grade ≥3 adverse events more frequently seen with chemotherapy plus necitumumab compared to chemotherapy were skin rash and hypomagnesemia. Based on these results, necitumumab has been approved as first-line therapy of squamous NSCLC in combination with gemcitabine and cisplatin. In contrast to the SQUIRE trial, the INSPIRE trial was prematurely stopped after enrolment of 634 patients because an interim analysis showed increased thrombo-embolic events and a lack of survival benefit for the combined treatment (6). Research has also focussed on the characterization of predictive biomarkers. Immunohistochemical EGFR protein expression and EGFR FISH positivity were of particular interest. In the FLEX trial, immunohistochemical EGFR expression of tumor cells was prospectively assessed by means of the DAKO pharmDx[TM] kit (7). Membrane staining intensity was divided into no staining, weak staining (1+), intermediate staining (2+), and strong staining (3+). The fractions of cells at the various staining intensities were determined. An immunohistochemistry score (IHC) based on both intensity and frequency of staining was then used for further analysis on the association between EGFR expression levels and clinical outcome. Patients were divided into those with high (IHC score ≥200) and those with low (IHC score <200) EGFR expression. High EGFR expression was seen in 31% of the patients. Among patients with high EGFR expression, patients treated with chemotherapy plus cetuximab had prolonged survival compared to those treated with chemotherapy alone. The hazard ratio was 0.73 (95% CI 0.58–0.93; p=0.011), median survival times were 12.0 and 9.6 months, and 1-year survival rates were 50% versus 37%. Among patients with low EGFR expression, survival times were not different between the two treatment arms. The treatment interaction between EGFR expression levels and treatment effect was statistically significant (p=0.04). The survival benefit achieved by the addition of cetuximab to chemotherapy in patients with high EGFR expression was seen across most subgroups including all major histological subgroups. Among patients with squamous NSCLC and high EGFR expression, the hazard ratio was 0.62 (0.43-0.88) in favour of cetuximab plus chemotherapy compared to chemotherapy alone. The survival benefit by the addition of cetuximab to chemotherapy in patients with high EGFR expression was achieved without an increase in toxicity. In summary, patient selection based on EGFR expression levels resulted in a clinically meaningful improvement in the risk benefit assessment of platinum-based first-line chemotherapy plus cetuximab in patients with advanced NSCLC (7). The SWOG S0819 biomarker validation study indicated that EGFR FISH positivity predicted benefit from cetuximab, particularly in patients with squamous NSCLC (8). Similarly, the benefits from necitumumab appeared to be greater in patients with EGFR FISH positivity or high EGFR expression (5, 9-10). References 1. Pirker R et al. Curr Opin Oncol 2015, 27, 87-93 2. Pirker R et al. Lancet 2009, 373, 1525-31 3. Lynch TJ et al. J Clin Oncol 2010, 28, 911-7 4. Pujol JL et al. Lung Cancer 2014, 83, 211-8 5. Thatcher N et al. Lancet Oncol 2015, 16, 763-74 6. Paz-Ares L et al. Lancet Oncol 2015, 16, 328-37 7. Pirker R et al. Lancet Oncol 2012, 13, 33-42 8. Herbst R et al. J Thorac Oncol 2015, 10, S795 9. Hirsch F et al. J Thorac Oncol 2015, 10, S797 10. Paz-Ares L et al. Ann Oncol 2016, 27, 1573-9

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