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Silvia Novello



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    MA04 - Novel Approaches with IO (ID 900)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
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      MA04.03 - Immunotherapy for Non-Small Cell Lung Cancers (NSCLC) with Oncogenic Driver Mutations: New Results from the Global IMMUNOTARGET Registry (ID 13187)

      13:40 - 13:45  |  Author(s): Silvia Novello

      • Abstract
      • Presentation
      • Slides

      Background

      Prospective data on immunotherapy for NSCLC with oncogenic driver mutations are limited. We recently reported first results from the global IMMUNOTARGET registry (Mazières, ASCO 2018). Here, we present new data for PD-L1 and mutation subgroups.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In 2017, we started an international retrospective registry study ("IMMUNOTARGET") for patients with advanced NSCLC, known driver mutations (KRAS, EGFR, ALK, ROS1, BRAF, HER2, MET and RET) and PD-L1 immune checkpoint inhibitor therapy. The registry is approved by University of Toulouse and Swissethics, and funded by University of Toulouse and Cantonal Hospital of Lucerne. Anonymized real-world data submitted to the coordinating center include: patient and tumor characteristics, mutation test methods and results, systemic therapy lines, immune related adverse events, best response by RECIST, survival, and tumor PD-L1 expression (optional). Statistical calculations including best response, median PFS and OS are done at University of Toulouse.

      4c3880bb027f159e801041b1021e88e8 Result

      In April 2018, the registry included 551 pts from Europe, USA, Israel and Australia. Patients were 50% male/female, 28% current smokers, median age 60 years (range 28-83), 85% had PS0/1. Most (73%) tumors were stage IV at diagnosis, almost all (96%) were adenocarcinomas. Molecular classification by dominant driver mutation: KRAS=271 (49%), EGFR=125 (23%), BRAF=43 (8%), MET=36 (7%), HER2=29 (5%), ALK=23 (4%), RET=16 (3%), ROS1=7 (1%), 1 (0.2%) not classified (ALK+RET+MET). Most pts received nivolumab (466) or pembrolizumab (48) and were treated with immunotherapy in second or third line (67%). The median number of cycles was 5 (range 1-68). Fifty (11%) pts had grade 3-5 toxicity. Median OS from start of immunotherapy was 13.3 months, median PFS was 2.8 months. Best response was PR/CR in: KRAS=26%, BRAF=24%, ROS1=17%, MET=16%, EGFR=12%, HER2=7%, RET=6%, ALK=0%. Percentage of PD-L1 positive cells was available for 177 pts: 0%=71 (40%), 1-49%=46 (26%), 50-100%=60 (34%). Median % of positive cells was highest for ROS1 (90%), BRAF (50%), MET (30%) and RET (26%) mutant tumors. PD-L1 positivity was predictive for improved PFS in KRAS and EGFR mutant tumors. PD-L1 status was known in 18 tumors with ALK, ROS1 or RET rearrangements: 5 had 0%, 4 had 1-49% and 9 had 50%-100%. No tumor remissions were observed in this subgroup. The registry remains open, updated results will be presented at the conference.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Although response rates were lower than in KRAS mutant NSCLC, individual tumors with other driver mutations responded to immunotherapy. PD-L1 expression may not accurately predict clinical benefit from immunotherapy in some molecular subgroups, better markers are needed.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Oligometastatic NSCLC
    • Presentations: 3
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
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      MA25.01 - EORTC Lung Cancer Group Survey to Define Synchronous Oligometastatic Disease in NSCLC (ID 13770)

      13:30 - 13:35  |  Author(s): Silvia Novello

      • Abstract
      • Presentation
      • Slides

      Background

      Synchronous oligometastasic disease (sOMD) has been described as a separate disease entity; however there is no consensus on what specific criteria constitutes sOMD in NSCLC. A consensus group (CG) was formed aiming to agree on a common sOMD definition (sOMD-d) that could be used in future clinical trials. A European survey was circulated to inform the discussion on sOMD-d.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      An EORTC Lung Cancer Group (LCG) / sOMD-d CG survey containing 31 questions on sOMD-d was distributed between 14/12/17 and 19/02/18 to EORTC LCG, sOMD-d CG, and several European thoracic oncology societies’ members.

      4c3880bb027f159e801041b1021e88e8 Result

      444 responses were analyzed (radiation oncologist: 55% [n=242], pulmonologist: 15% [n=66], medical oncologist: 14% [n=64]; 78% with >5 years’ experience in treating NSCLC). Belgium (14%, n=62), Italy (12%, n=55), Germany (11%, n=47), and Netherlands (10%, n=44) contributed most. 81% (n=361) physicians aimed to cure sOMD NSCLC patients and 82% (n=361) included the possibility to treat the patient with radical intent in their sOMD-d. The maximum number of metastases considered in sOMD-d varied: 19%, 42%, 4%, and 17% replied <2, 3, 4, and >5 metastases, respectively. 79% (n=353) stated that the number of organs involved was important for sOMD-d, and most (80%, n=355) considered that only <3 involved organs (excluding primary) should be included in the definition. 317 (71.7%) allowed mediastinal lymph node involvement (MLN) in the sOMD-d, and 22.1% of them counted MLN as a metastatic site. For 195/327 (60%), when N2/N3 disease is included in the sOMD-d, there is no specific issue regarding the MLN volume/location as long as radical treatment is possible. 384 (86%) considered pulmonary metastasis (outside primary tumor: M1a) as metastatic site. Most physicians confirmed sOMD patients with brain MRI (91%, n=403) and PET-CT (98%, n=437). For mediastinum staging, most (64%, n=285) respondents stated that histology/cytology should be obtained when PET-CT shows suspected lymph nodes or in case of a central primary tumor. Pathology proof of metastatic disease was necessary in sOMD for 315 (71%) physicians, and 37% (n=163) acknowledged that histology should be obtained from at least from one metastatic site. Preferred primary outcome parameter in clinical trials of sOMD was overall survival (73%, n=325).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Although certain consensual answers were obtained (81% aimed to cure and >90% mandated baseline imaging with PET-CT and brain MRI), a number of issues remain unresolved and will require further discussion by a panel of experts to agree on a sOMD-d.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA25.02 - Searching for a Definition of Synchronous Oligometastatic (sOMD)-NSCLC: A Consensus from Thoracic Oncology Experts (ID 13452)

      13:40 - 13:45  |  Author(s): Silvia Novello

      • Abstract
      • Presentation
      • Slides

      Background

      Recent prospective single centre studies reported improved outcomes in patients with sOMD-NSCLC who were treated with radical intent. Since then sOMD has been perceived as a separate disease entity. However, a clear definition of sOMD-NSCLC is lacking. We aimed to develop a definition and diagnostic criteria of sOMD-NSCLC following a consensus process.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A European multidisciplinary consensus group was established with representatives from different scientific societies. Consensus questions were extracted from a survey, case series and a systematic review. The questions were discussed, and the statement formulated during a consensus meeting in Dublin (23.01.18).

      4c3880bb027f159e801041b1021e88e8 Result

      Summary of consensus statement

      Defining sOMD-NSCLC

      Definition of sOMD is relevant for patients in whom a radical treatment is technically feasible with acceptable toxicity, taking into account all sites, that may modify the course of the disease leading to a long-term disease control.

      All sites must be technically and safely treatable.

      The maximum number of metastases/organs meeting the criteria involved will depend on the possibility of offering a treatment strategy with radical intent, taking into account local control and toxicity. Based on the systematic review, a maximum of 5 metastases and 3 organs is proposed.

      Diffuse serosal metastases and bone marrow involvement are excluded.

      Mediastinal lymph node (MLN) involvement should be considered as locoregional disease in the definition of sOMD-NSCLC.

      MLN involvement is of importance in determining if a radical local treatment of the primary tumour may be applied and the MLN will not be counted as a metastatic site.

      Staging of sOMD-NSCLC

      PET-CT and brain imaging are considered mandatory.

      In case of a solitary liver metastasis a dedicated MRI of the liver and for a solitary pleural metastasis, thoracoscopy and biopsies of distant ipsilateral pleural sites are advised.

      Staging of the mediastinum requires a minimum of a FDG-PET scan, with pathological confirmation preferred if this influences the treatment strategy.

      Pathological proof is required unless the MDT decides that the risk outweighs the benefit. Pathology proof is advised for single metastatic location and if it may change the therapeutic strategy, confirmation of the MLN involvement is recommended.

      8eea62084ca7e541d918e823422bd82e Conclusion

      A multidisciplinary consensus statement on the definition and staging of sOMD-NSCLC was formulated taking into account results of a European survey, a systematic review and case discussion. This statement might be helpful to standardise inclusion criteria in future clinical trials. However, the definition of sOMD may change over time when more prospective data will become available.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA25.03 - Defining Oligometastatic Non-Small Cell Lung Cancer (NSCLC): An Evolving Multidisciplinary Expert Opinion (ID 12573)

      13:35 - 13:40  |  Author(s): Silvia Novello

      • Abstract
      • Presentation
      • Slides

      Background

      Synchronous oligometastatic NSCLC definition varies between: 1 metastasis in 1 organ (TNM8), 1-3 metastases (ESMO), ≤3 metastases after systemic treatment with mediastinal nodes (MLN) counting as 1 site (Gomez, Lancet Oncol 2016) to 3-≥5 metastases in ongoing trials. A single definition is however needed to design and compare trials. To assess synchronous oligometastatic NSCLC definitions used by clinical experts in daily practice and its evolution, we redistributed a 2012-case based survey (Dooms et al, presented at WCLC 2013).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In December 2017, 10 real-life multidisciplinary team (MDT) discussed patients (all good condition, no significant comorbidities, 18FFDG-PET and brain MRI staged, all < 5 metastases, 9/10 ≤ 3 metastases, oncogene-addicted or wildtype NSCLC) were distributed to 33 international NSCLC experts involved in the EORTC oligometastatic NSCLC consensus group, questioning: 1) can you discuss these cases in your MDT?, 2) do these patients have oligometastatic disease? and 3) what is your treatment proposal for the oligometastatic disease patients? Current answers were compared to the previous ones, and the real-life treatment and survival of the patients was added.

      4c3880bb027f159e801041b1021e88e8 Result

      26/33 experts (24 centers) replied: 8 medical oncologists, 7 pulmonologists, 7 radiation oncologists, 4 thoracic surgeons. 62% discussed the cases in their MDT. 1 case had 100% oligometastatic disease consensus, 3 cases had > 90% consensus, the number of treatment proposals varied between 3 to 8 (Table). Radical treatment was more often offered in case of a single metastasis or N0 status. Compared to 2012 there was a trend towards a more conservative oligometastatic definition and chemotherapy was more often included in the treatment proposal.

      table 1
      Case TNM8

      oligometastatic

      yes answer %

      2012 / 2017

      Number of tx

      proposals

      2012 / 2017

      Radical tx

      answers %

      2012/2017

      Real life radical

      tx intent

      real life survival

      (months) /

      5Y survival

      EGFR+ T2aN3M1c (3 brain mets) 55 / 38 2 / 5 27 / 23 - 40.1 / -
      EGFR+ T4N0M1a (ground glass) 36 / 35 4 / 3 45 / 35 + 65.2 / +
      T2aN1M1b (solitary renal) 91 / 96 5 / 5 100 / 92 + 8.3 / -
      T1bN3M1b (solitary adrenal) 73 / 58 4 / 5 36 / 54 + 66.1 / +
      T2bN1M1c (adrenal + pelvic node) 55 / 50 2 / 5 36 / 46 - 18.6 / -
      T2aN0M1c (3 liver mets) 64 / 69 4/ 5 27 / 62 - 51.5 / -
      T2aN2M1b (solitary bone) 91 / 92 4 / 5 73 / 85 + 13.4 / -
      T3N1M1c (2 brain mets) 91 / 96 3 / 8 73 / 85 + 39.6 / -
      T2aN0M1c (1 lung, 1 pancreas) 82 / 69 5 / 4 64 / 50 + 74.0 / +
      T1bN0M1b (solitary bone) 100 / 100 3 / 5 82 / 92 + 11.6 / -

      8eea62084ca7e541d918e823422bd82e Conclusion

      Synchronous oligometastatic NSCLC definition was more conservative than in 2012 and linked to radical intent of treatment. Number of organs, MLN status and possibility for radical treatment seem to be components of daily practice synchronous oligometastatic definition.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    MA26 - New Therapies and Emerging Data in ALK, EGFR and ROS1 (ID 930)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 201 BD
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      MA26.02 - Upfront or Sequential Strategy for New Generation Anaplastic Lymphoma Kinase (ALK) Inhibitors: An Italian Retrospective Study.  (ID 12790)

      13:35 - 13:40  |  Author(s): Silvia Novello

      • Abstract
      • Presentation
      • Slides

      Background

      Anaplastic lymphoma kinase (ALK) rearrangement confers sensitivity to ALK inhibitors (ALKis) in non-small-cell lung cancer (NSCLC). Although several drugs provided an impressive outcome benefit, the most effective sequential strategy is still unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively collected 242 ALK-positive advanced NSCLC diagnosed between 2010 and 2018 in 23 Italian institutions (expanded data collection from Gobbini et al. Lung Cancer 2017). 138 patients received exclusively crizotinib as ALKi (not considered for this analysis). 78 patients received crizotinib and a new (second or third) generation ALKis as further treatments (group A). 26 patients performed a new generation ALKi as upfront agent (group B). These groups are larger than those considered in a previous analysis (15 and 8 patients, respectively).

      4c3880bb027f159e801041b1021e88e8 Result

      Study population clinical features and treatments received are summarized in Table 1.

      Group A

      Crizotinib followed by new generation ALKis

      N= 78

      Group B

      Upfront new generation ALKis

      N=26

      Treatments per line n(%)

      Crizotinib

      28(36)

      50(64)

      -

      -

      -

      -

      2(8)

      -

      Alectinib

      -

      11(14)

      18(23)

      5(17)

      7(27)

      -

      -

      -

      Ceritinib

      -

      9(12)

      23(30)

      3(4)

      8(31)

      8(31)

      1(4)

      -

      Brigatinib

      -

      6(8)

      6(8)

      2(3)

      -

      2(8)

      -

      2(8)

      Lorlatinib

      -

      -

      4(5)

      5(6)

      -

      -

      1(4)

      -

      Chemotherapy

      50(64)

      2(3)

      10(13)

      na

      11(42)

      6(23)

      1(4)

      Na

      Clinical features n(%)

      Age (range)

      58 (27-83)

      55 (24-82)

      Male

      37(47)

      10(38)

      p= 0.42

      Female

      41(53)

      16(62)

      Current smoker

      8(10)

      5(19)

      p= 0.23

      Never/former smoker

      70(90)

      21(81)

      ALKi beyond PD

      27(34)

      4(15)

      p= 0.06

      With a median follow-up of 22.6 months (CI 95% 20.09-25.10), 33 patients had died (32%). In group B, the median progression free survival (PFS) for new generation ALKis administered as first (14.0 months, CI 95% 9.52-18.471), second (12.7 months, CI95% 7.22-18.17) or third-line (12.8 months, CI95% 6.24-19.35) was not statistically different (p= 0.522). The median time from the start of crizotinib to the disease progression after the new generation ALKi sequentially performed (group A) was longer than that one detected in group B for the upfront new generation ALKis (29 vs 14 months, HR 2.47 [CI95% 1.35-4.50], p=0.003). This result was confirmed even considering the time lost between the two treatments in group A. The median overall survival (OS) was not reached. The 12-months OS rate was 97% in group A and 84% in group B.

      8eea62084ca7e541d918e823422bd82e Conclusion

      New generation ALKis maintain their efficacy regardless of the treatment setting considered. The sequential strategy seems to provide a substantial benefit, but a longer follow-up and larger samples are needed to clarify the survival impact.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    MS07 - Antibody-Drug Conjugates in Advanced NSCLC (ID 786)

    • Event: WCLC 2018
    • Type: Mini Symposium
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 205 BD
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      MS07.04 - Future Directions (ID 11431)

      14:30 - 14:50  |  Presenting Author(s): Silvia Novello

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    OA05 - Clinical Trials in IO (ID 899)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 106
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      OA05.07 - IMpower132: PFS and Safety Results with 1L Atezolizumab + Carboplatin/Cisplatin + Pemetrexed in Stage IV Non-Squamous NSCLC (ID 12389)

      14:35 - 14:45  |  Author(s): Silvia Novello

      • Abstract
      • Presentation
      • Slides

      Background

      In addition to the combination of atezolizumab (anti–PD-L1)+platinum+taxane±bevacizumab, non-squamous NSCLC patients may derive benefit from adding atezolizumab to platinum+pemetrexed. The randomized Phase III IMpower132 study (NCT02657434) evaluated first-line pemetrexed+carboplatin or cisplatin±atezolizumab in patients with stage IV non-squamous NSCLC without EGFR or ALK driver mutations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients were randomized 1:1 to receive 4 or 6 cycles of carboplatin AUC 6 mg/mL/min or cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 Q3W alone (arm PP) or in combination with atezolizumab 1200 mg Q3W (arm APP), followed by pemetrexed (arm PP) or atezolizumab + pemetrexed (arm APP) maintenance. Atezolizumab could be continued beyond disease progression per protocol guidelines. PFS and OS were co-primary endpoints. Efficacy by PD-L1 expression was an exploratory endpoint. Here, we present investigator-assessed PFS per RECIST v1.1 (final analysis), OS (interim analysis) and safety data.

      4c3880bb027f159e801041b1021e88e8 Result

      292 pts were enrolled in arm APP and 286 pts in arm PP. 43% and 40% in arms APP and PP, respectively, had ECOG PS 0. At the data cutoff (22 May 2018), median follow-up was 14.8 mo overall. PFS analysis showed a statistically significant improvement between arm APP vs PP (median PFS 7.6 vs 5.2 mo; HR=0.596; 95% CI: 0.494, 0.719; P<0.0001). Interim analysis showed a numerical but non-statistically significant OS improvement (Table). Efficacy results were consistent across all key clinical subgroups. Grade 3-4 TRAEs occurred in 53.6% of patients (APP) vs 39.1% (PP). 7.2% of patients (APP) vs 5.1% (PP) had a Grade 5 AE, 3.8% (APP) vs 2.6% (PP) were treatment related. 48.5% of patients (APP) vs 38.0% (PP) experienced AEs of special interest specific to atezolizumab.

      8eea62084ca7e541d918e823422bd82e Conclusion

      IMpower132 met its co-primary endpoint of investigator-assessed PFS in the ITT. Interim OS data (not fully mature) showed numerical improvement. Atezolizumab+pemetrexed+carboplatin or cisplatin was well tolerated, and no new safety signals were identified.

      Table. IMpower132 Efficacy Analyses

      APP Arm
      (atezolizumab+pemetrexed+ carboplatin or cisplatin)
      PP Arm
      (pemetrexed+carboplatin or cisplatin)
      ITT n=292 n=286
      Median PFS (95% CI), mo 7.6 (6.6, 8.5) 5.2 (4.3, 5.6)
      HRa (95% CI; P value) 0.596 (0.494, 0.719; P < 0.0001)
      12-Month PFS (95% CI), % 33.7% (28.2, 39.2) 17.0% (12.6, 21.4)
      Median OS (95% CI), mo 18.1 (13.0, NE) 13.6 (11.4, 15.5)
      HRa (95% CI; P value) 0.813 (0.644, 1.025; P = 0.0797)
      12-Month OS (95% CI), % 59.6% (53.9, 65.3) 55.4% (49.5, 61.2)
      ORR (confirmed, inv-assessed), % 46.9% 32.2%
      DOR (95% CI), mo 10.1 (7.2, 13.3) 7.2 (5.7, 9.0)
      PD-L1–highb n=25 n=20
      Median PFS (95% CI), mo 10.8 (7.9, NE) 6.5 (2.4, 10.6)
      HR (95% CI; P value) 0.464 (0.224, 0.960; P = 0.0339)
      PD-L1–lowb n=63 n=73
      Median PFS (95% CI), mo 6.2 (4.4, 8.4) 5.7 (4.2, 7.9)
      HR (95% CI; P value) 0.804 (0.556, 1.163; P = 0.2462)
      PD-L1–negativeb n=88 n=75
      Median PFS (95% CI), mo 8.5 (6.1, 11.2) 4.9 (4.2, 5.8)
      HR (95% CI; P value) 0.448 (0.313, 0.642; P < 0.0001)

      DOR, duration of response; HR, hazard ratio; inv, investigator; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.

      a Stratified. b Baseline tissue available in 60% of patients. PD-L1high (TC3/IC3): patients with PD-L1 expression in ≥50% of tumor cells or ≥10% of tumor-infiltrating immune cells; PD-L1low (TC12/IC12): patients with PD-L1 expression in ≥1% and <50% of tumor cells or ≥1% and <10% of tumor-infiltrating immune cells; and PD-L1negative (TC0/IC0): patients with PD-L1 expression in <1% of tumor cells and <1% of tumor-infiltrating immune cells.

      NCT02657434

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-68 - Correlation of the Lung Immune Prognostic Index (LIPI) and PDL1 Status with Outcomes for Immune Checkpoint Inhibitors in Advanced NSCLC Patients (ID 14256)

      16:45 - 18:00  |  Author(s): Silvia Novello

      • Abstract

      Background

      Baseline LIPI, based on derived NLR (neutrophils/[leucocytes-neutrophils]) and lactate dehydrogenase (LDH) was associated with outcomes for immune checkpoint inhibitors in advanced NSCLC patients. We assessed the correlation between LIPI and PDL1 for ICI outcomes in NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Baseline dNLR and LDH and clinical data were retrospectively collected in advanced NSCLC patients, treated with PD1/PDL1 +/- CTLA4 inhibitors from Nov. 2012 to Mar. 2018, in a multicentric cohort (N=794) from 11 centers. LIPI stratified 3 groups: good (dNLR<3+LDH<upper limit of normal (ULN), intermediate (dNLR>3 or LDH>ULN), poor risk (dNLR>3+LDH>ULN). PDL1 positivity was defined as ≥ 1% tumor cells expression by immunohistochemistry.

      4c3880bb027f159e801041b1021e88e8 Result

      476 patients (60%) were male, 693 (87%) smokers, 695 (88%) had PS ≤1, with median age 65; 576 (73%) had nonsquamous histology. PDL1 was ≥ 1% in 195 (70%) patients, negative in 82 (30%), and unknown in 517. The median of prior lines was 1 (0-11). The median PFS and OS were 4 months (m) [95% CI 4-5] and 12 m [10-15]. dNLR was>3 in 276 (35%) and LDH>ULN in 290 (37%) patients. LIPI stratified 349 patients as good (44%), 323 (41%) as intermediate and 121 (15%) as poor LIPI risk groups. LIPI was an independent factor for OS (table) and PFS (HR 2.58; CI 1.3-5.2, P=0.02). ≥ 1% PDL1 and ≥ 50% PDL1 were not correlated with OS and PFS. Median OS for good, intermediate, and poor LIPI risk groups were 21 m [17-23], 11 m [9-14] and 4 m [2-6], respectively (P=<0.0001). Median PFS for good, intermediate, and poor risk was 5 m [5-7], 4 m [3-5], and 2 m [1-3], respectively (P=0.0005). No differences were observed in LIPI groups according to the PDL1 expression.

      Multivariate analysis for OS

      HR

      95% CI

      P value

      Immunotherapy line

      >2

      2.117

      0.641

      6.992

      0.219

      N# Metastasis sites

      ≥2

      1.242

      0.727

      2.121

      0.428

      Performance status

      ≥2

      2.141

      1.059

      4.332

      0.034

      Albumin

      >35 g/dL

      0.867

      0.507

      1.48

      0.6

      LIPI

      Intermediate

      Poor

      1.697

      4.178

      0.917

      1.956

      3.142

      8.925

      0.001

      PDL1 IHC

      ≥1%

      0.713

      0.406

      1.252

      0.239

      8eea62084ca7e541d918e823422bd82e Conclusion

      Baseline LIPI is associated with ICI outcomes in advanced NSCLC, regardless the PDL1 expression. LIPI should be evaluated in prospective clinical trials.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.01-73 - Preliminary Results of the SENECA (SEcond Line NintEdanib in Non-Small Cell Lung CAncer) Trial: An Italian Experience. (ID 13281)

      16:45 - 18:00  |  Presenting Author(s): Silvia Novello

      • Abstract
      • Slides

      Background

      Nintedanib is a multi-target small-molecule with anti-angiogenetic activity which confers longer progression free survival (PFS) and overall survival (OS) as second-line combination treatment with docetaxel versus standard-of-care, in non-squamous non-small cell lung cancer (nsNSCLC) patients, giving to rapidly progressing patients the greatest survival benefit. Considering the higher tolerability of weekly docetaxel than docetaxel q3wks in the real-life, the SENECA trial, a phase IIb, open label, Italian multicentre study, aims to evaluate whether treatment with nintedanib and docetaxel could be effective and safe as second-line option in nsNSCLC patients with the two different schedules.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients from eighteen Italian oncologic centres, with stage IIIB/IV non-oncogene addicted nsNSCLC patients, progressing after first-line chemotherapy, have been treated with docetaxel (T1: 33 mg/mq on days 1 and 8 in a 21-days cycle; T2: 75 mg/mq q3wks) plus continuous oral nintedanib, with the possibility of maintenance in case of stabilization or response. Primary endpoint was PFS (by investigator’s assessment), while secondary endpoints included OS, safety and quality-of-life. Study stratifies patients into two cohorts according to relapse-timing (within or over 3 months) from end of first-line chemotherapy.

      4c3880bb027f159e801041b1021e88e8 Result

      From January 2016 to data cut-off, on 30th March 2018, 197 patients have been evaluated: 30 were registered as screening failures, mainly for contraindications to nintedanib use. The 167 patients considered in this preliminary analysis had a median age of 63.4 years (range 35-86), were predominantly male (68.9%), smokers or former-smokers (84.4%) and with ECOG-performance status 0 (72.5%). According to investigator’s choice, 82 patients have been treated with T1 docetaxel (49.1%), 85 (50.9%) with T2 docetaxel (median docetaxel treatment 3.5 and 3.7 21-days cycles, respectively). No significant differences in median PFS have been observed between T1 and T2 (3.83 vs 4.32 months, respectively; HR 0.889 [95% IC 0.598-1.321], p-value=0.559). After a median follow-up of 7.28 months (standard deviation=5.55), a trend of similar OS has emerged in both T1 and T2 (6.63 vs 7.91 months, respectively; HR 0.770 [95% IC 0.484-1.225], p-value=0.270). Survival data of relapse-timing cohorts are not yet mature. Commonest toxicities in T1 and T2 were: fatigue (53.6% vs 65.9%, respectively), diarrhea (50.0% vs 47.0%), afebrile neutropenia (13.4% vs 52.9%) and ALT elevation (29.3% vs 20.0%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The SENECA trial is a real-life Italian experience, whose preliminary results confirm the efficacy and safety of second-line treatment with nintedanib and docetaxel for nsNSCLC patients, regardless from docetaxel schedule, suggesting higher toxicities for docetaxel q3wks.

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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-20 - MET Protein Expression and Activation During Targeted Therapy in EGFR Mutated Lung Adenocarcinoma (ID 13478)

      16:45 - 18:00  |  Presenting Author(s): Silvia Novello

      • Abstract
      • Slides

      Background

      In EGFR mutated (EGFRm) lung adenocarcinoma (ADC) the tyrosine kinase (TK) receptor MET is involved in acquired resistance to anti-EGFR treatment. We analyzed MET protein expression and activation in EGFRm lung ADC treated with TK inhibitors (TKI).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with advanced EGFRm lung ADC, treated at the Oncology Department - San Luigi Hospital, who underwent tissue biopsy for diagnosis and tissue re-biopsy at disease progression for T790M test (after a negative liquid biopsy) were selected. c-MET (clone SP44) and phosphorylated (p-) MET (Tyr1234/1235, D26) expression was analyzed by immunohistochemistry and evaluated as H-Score (HS).

      4c3880bb027f159e801041b1021e88e8 Result

      Tumor tissues from 18 advanced EGFRm patients (12 female and 6 male; mean age 59 years) were available. On April 2018, 10 patients were alive and 8 were died. 11/18 (61%) cases harbored a T790M point mutation (T790M+) detected at tissue re-biopsy.

      At the baseline tumor tissue, lower c-MET expression levels were found in T790M+ (mean HS value= 135, range 40-250) compared to the T790M negative (T790M-) group (mean HS value= 226, range 100-300) (p=0.02). Furthermore, in T790M+ patients p-MET was expressed in 2/11 cases (18%, HS values=5 and 60) while in the T790M- group p-MET was expressed in 3/7 (43%, HS values=5, 240 and 240) cases (although with no significant p value).

      After first line TKI treatment, in the T790M+ group c-MET expression (mean HS value=140, range 5-300) was augmented in 7 and reduced in 4 cases, while p-MET was positive in 2/11 cases (HS values of 300 and 30). No significant differences in survival were found.

      In the T790M- group the c-MET mean HS value was 152 (range 30-300) and the 4/7 cases with higher c-MET expression levels (HS> 152) had a significant shorter PFS (p=0.02, HR=0.3, median survival: 7.5 vs 24 months). Furthermore, in this group p-MET positivity was maintained in the same 3 cases (with HS values= 240, 180, 10) and the two patients with higher MET activation had short PFS (9 and 6 months) at first line TKI treatment.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our preliminary analyses suggest that a strong expression of basal c-MET receptor in advanced EGFRm ADC may predict a T790M negative status at disease progression. Furthermore MET higher expression and activation may play a role in acquired resistance to TKI, although a limited number of cases have been analyzed. Thereby, we propose to monitor MET status along treatment and to reconsider MET-directed therapies for a well-selected subset of EGFRm lung ADC patients.

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    P2.09 - Pathology (Not CME Accredited Session) (ID 958)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.09-21 - Women with Synchronous or Metachronous Lung and Ovarian Cancers: A Multi-Institutional Report (ID 12485)

      16:45 - 18:00  |  Presenting Author(s): Silvia Novello

      • Abstract
      • Slides

      Background

      In women, lung cancer (LC) and ovarian cancer (OC) are, respectively, the second and eighth malignancies for incidence in developed Countries. Despite increasing incidence and mortality of LC, association with OC is rare and no literature data are available on this topic yet. Our aim was to describe a series of patients with synchronous or metachronous LC and OC and to identify common clinical and pathological patterns.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrieved the medical charts of patients who referred to 30 European Oncological Institutes from 2008 to 2018. When patients with synchronous (up to 3 months of time interval in onset) or metachronous LC and OC were found, we collected detailed medical history, pathological features and clinical outcomes. Whenever available, formalin fixed paraffin embedded tumor tissue from both specimens was collected for centralized pathology revision with an immunohistochemical marker panel including TTF-1 and PAX-8. In ambiguous cases, a broader panel was performed (p40, CK-7, WT1, CA125, Calretinin, EMA, CEA, CgA, Vimentin, Napsin-A). Whenever tested, genetic alterations in LC and OC were also reported.

      4c3880bb027f159e801041b1021e88e8 Result

      As of April 2018, among 30 European Oncological Centers (Italy, France, Slovenia), 11 retrieved in their series patients with a history of LC and OC, for a total of 18 cases in the last 10 years. Paired histological specimens were available in 6 cases. One patient was excluded, since pathology revision revealed that lung lesions were metastases from serous OC. Thus, analyses were performed on 17 patients. In 10/17 cases (58.8%), LC and OC were metachronous and, in 6/10 cases, OC preceded LC diagnosis, with a median interval of 4.5 years. Median age at diagnosis of the first malignancy was 62 years, the majority of patients (64.7%) were never-smoker, 6 had cancer familial history. Interestingly, 4 patients (23.5%) reported also a third or fourth malignancy. After a median follow-up of 6.5 years, 10 patients are alive. Regarding histology, most of LC were adenocarcinoma (14/17, 82.3%). Molecular status was available in 9/14 cases: 4 had EGFR mutation, 1 B-RAF mutation and 2 ALK translocation. OC were mostly high-grade serous (83,3%). BRCA status was available in 6 patients: 2 mutated, 2 wild-type and 2 affected by variants of unknown significance (USV). Moreover, one synchronous case presented both BRCA-USV and B-RAF mutation.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In our series, synchronous and metachronous LC and OC were often driven by genetic alterations. Further genetic analysis with next generation sequencing technology has already been planned.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 961)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.12-04 - Liposomal Irinotecan vs Topotecan in Patients with Small Cell Lung Cancer Who Have Progressed On/After Platinum-Based Therapy (ID 12768)

      16:45 - 18:00  |  Author(s): Silvia Novello

      • Abstract
      • Slides

      Background

      Small Cell Lung Cancer (SCLC) accounts for ~15% of all lung cancers; it is an aggressive disease marked by rapid growth and early metastasis. Patients typically demonstrate initial sensitivity to chemotherapy and radiotherapy, followed by rapid relapse and development of drug resistance. Topotecan, a topoisomerase I (TOP1) inhibitor, is the only agent approved for second-line treatment in the United States and Europe. Liposomal irinotecan (nal-IRI) has demonstrated sustained TOP1 inhibition, with liposomal deposition in tumor tissue through leaky vasculature, followed by irinotecan release and subsequent conversion to the active metabolite SN-38. Pre-clinical data suggests that nal-IRI has improved anti-tumor activity compared to topotecan. The current trial (NCT03088813) is being undertaken to investigate the safety and efficacy of nal-IRI versus intravenous topotecan in patients with SCLC who have progressed on or after platinum-based first-line therapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      There are two parts of this study: Part 1 is an open-label, single-arm, safety run-in phase and Part 2 is a randomized, controlled, efficacy assessment phase. Key inclusion criteria include ECOG performance status of 0–1, adequate organ function, histopathologically/cytologically confirmed SCLC, evaluable disease (RECIST v1.1), and life expectancy ≥12 weeks. Prior exposure of immuno-oncology therapies is allowed. Key exclusion criteria include a diagnosis of large cell neuroendocrine lung carcinoma, prior treatment regimens with TOP1 inhibitors, and retreatment with the same platinum-based regimen after relapse of first-line therapy. In Part 1, patients will be treated with different doses of nal-IRI to identify a tolerable dose level; this dose level will be expanded to include a total of 24 patients. The primary endpoint is safety and tolerability, with secondary endpoints including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

      In Part 2, ~450 patients will be randomized in a 1:1 ratio between nal-IRI and IV topotecan. The primary endpoint is OS, followed by PFS, ORR, patient-reported outcomes, and exploratory analyses. Patients will be treated for a minimum of 3 cycles (1 cycle = 6 weeks) or until progressive disease or unacceptable toxicity. Safety analyses will be performed using the safety population, defined as all patients receiving any study drug.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable - Trial in progress

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section not applicable - Trial in progress

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.08 - Oligometastatic NSCLC (Not CME Accredited Session) (ID 974)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.08-04 - OMEGA, A Randomized Trial of Local Ablative Therapy Vs. Conventional Treatment in Oligometastatic NSCLC – Trial in Progress (ID 13971)

      12:00 - 13:30  |  Author(s): Silvia Novello

      • Abstract
      • Slides

      Background

      A recent randomized phase 2 study has shown that local ablative therapy in addition to systemic treatment was superior to maintenance therapy in prolonging disease-free survival in NSCLC patients harboring up to three metastatic sites.

      Oligometastatic lung cancer (OM-NSCLC) seems thus to be associated with a better prognosis than usual Stage IV non-small cell lung cancer when radical local therapy of all metastatic sites is administered but the impact of such an approach on overall survival and quality of life remains unclear

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A consortium of tertiary referral centres involved in Lung Cancer management at the national level was established with the aim of setting up a randomized trial addressing this issue

      4c3880bb027f159e801041b1021e88e8 Result

      A randomized trial of local ablative therapy in OM-NSCLC patients with potentially resectable or locally controlled primary tumors has been designed and 7 tertiary referral centers agreed to participate

      Patients with synchronous or metachronous oligometastatic lung cancer (1-3 metastatic lesions) will be randomized to local ablative therapy + standard treatment Vs. standard treatment.

      Balancing between study arms will be performed according to synchronous vs. metachronous presentation, Number of oligometastases, Nodal status and Oncogene-addiction or PDL-1 expression.

      Primary outcome will be Overall Survival (OS) from randomization. The sample size is set to 195 patients.

      Inclusion criteria include adequate performance status, primary tumor controlled or controllable staging with whole-body FDG PET scan and brain MRI, fit to receive at least 3 cycles of platinum-based doublet chemotherapy, or immunotherapy or targeted agents according to molecular profile.

      Exclusion criteria include cerebral oligometastasis alone (will receive local therapy in any case),

      metastasis in sites where normal radiotherapy constraints cannot be met, multiple subsolid nodules in the absence of extrapulmonary metastasis, prior malignant tumor with some exceptions, relevant co-morbidities that would significantly reduce life expectancy on their own,

      Disease state and life status assessed on a 2-monthly basis by physical examination, whole-body CT scan plus repeat PET-scan if needed and Brain MRI if brain metastasis at enrolment. Toxicity and adverse events will be assessed according to NCI-Common Terminology Criteria. Quality of life will be assessed at randomization and after six months by the SF36/LCSS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      There is a clear need for randomized controlled trials with overall survival as their main endpoint to confirm whether local ablative therapy indeed has a role in the management of oligometastatic lung cancer. The Omega trial will try to respond to such a need.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)

    • Event: WCLC 2018
    • Type: Plenary Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
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      PL02.09 - Nintedanib + Pemetrexed/Cisplatin in Patients with Unresectable MPM: Phase III Results from the LUME-Meso Trial (ID 11192)

      09:15 - 09:25  |  Author(s): Silvia Novello

      • Abstract
      • Presentation
      • Slides

      Background

      Nintedanib targets VEGFR 1–3, PDGFR α/β, FGFR 1–3, Src and Abl kinases, all implicated in malignant pleural mesothelioma (MPM) pathophysiology. This global Phase II/III, randomised, double-blind study investigated pemetrexed/cisplatin in combination with nintedanib or pemetrexed/cisplatin in combination with placebo, followed by nintedanib or placebo maintenance, in patients with unresectable MPM. In the double-blind, randomised Phase II part, nintedanib plus pemetrexed/cisplatin improved PFS vs placebo (HR=0.56; 95% CI: 0.34–0.91; p=0.017; median 9.4 vs 5.7 months).

      In Phase III, chemotherapy-naïve patients with epithelioid MPM (ECOG PS 0–1) were randomised 1:1 to receive up to six cycles of pemetrexed (500 mg/m2)/cisplatin (75 mg/m2) on Day 1, plus nintedanib (200 mg bid) or matched placebo on Days 2–21. After combination treatment, patients without disease progression received nintedanib or placebo maintenance. The primary endpoint (PFS by investigator assessment) and key secondary endpoint (OS) were planned to be analysed by hierarchical testing, with an interim OS analysis at the time of the primary PFS analysis. PFS was also assessed by independent central review. Based on the assumed treatment effect (HR=0.63), the study had 90% power to detect a statistically significant and clinically meaningful improvement in PFS.

      In total, 458 patients were randomised. Baseline patient characteristics and oncological history were similar between treatment arms. Median duration of nintedanib or placebo administration was 5.3 and 5.1 months, respectively. After 250 events, there was no difference in PFS between nintedanib and placebo arms (HR=1.01; 95% CI: 0.79–1.30; p=0.91; median 6.8 vs 7.0 months, respectively). PFS by central independent review was similar (242 events; HR=0.99; 95% CI: 0.77–1.28; p=0.96; median 6.8 months in each arm). In the interim OS analysis (127 deaths [28% of events]), median OS was 14.4 vs 16.1 months (nintedanib vs placebo; HR=1.12; 95% CI: 0.79–1.58; p=0.54). There were no unexpected safety findings. The proportion of patients with Grade ≥3 AEs was higher with nintedanib than with placebo (72% vs 62%). The most frequently reported Grade ≥3 AE by medical concept in both treatment arms was neutropenia (nintedanib: 32%; placebo: 24%). The proportion of deaths due to serious AEs was 4.0% (nintedanib) and 7.5% (placebo).

      The primary endpoint of the Phase III part of LUME-Meso was not met ‒ Phase II findings were not confirmed. The reported safety profile was consistent with the known safety profiles of nintedanib and pemetrexed/cisplatin.

      a9ded1e5ce5d75814730bb4caaf49419

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