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Benjamin Besse



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    MA 02 - Emerging Targets (ID 656)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Clinical Design, Statistics and Clinical Trials
    • Presentations: 1
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      MA 02.02 - Phase 2 Study of Pembrolizumab Plus CC-486 vs Pembrolizumab Plus Placebo in Previously Treated Patients with Advanced NSCLC (ID 8581)

      11:00 - 12:30  |  Author(s): Benjamin Besse

      • Abstract
      • Presentation
      • Slides

      Background:
      Studies have demonstrated that epigenetic modifiers, such as azacitidine, may sensitize tumor cells to treatment with checkpoint inhibitors, such as pembrolizumab (pembro). Efficacy and safety results from a phase 2, randomized, double-blind study of pembro in combination with CC-486, an oral formulation of azacitidine, vs pembro+placebo (PBO) for 2L treatment of advanced NSCLC are reported.

      Method:
      Patients aged ≥ 18 years with stage IIIB/IV NSCLC with only 1 prior platinum-based chemotherapy were randomized 1:1 (stratified by histology) to pembro 200 mg day 1 plus either CC-486 300 mg or placebo days 1-14 of a 21-day cycle. Primary endpoint was PFS. Key secondary endpoints included OS, ORR and safety.

      Result:
      51 and 49 patients were randomized to the pembro+CC-486 and pembro+PBO arms. Baseline characteristics were generally balanced between treatment groups. Efficacy results are shown in Table 1. Median duration of treatment for pembro+CC-486 vs pembro+PBO was 14 vs 24 weeks, and median number of cycles was 5 vs 7. The most common grade 3/4 TEAEs associated with pembro+CC-486 were nausea (14%), vomiting (12%), asthenia (10%), and diarrhea (8%), vs diarrhea (6%), asthenia (6%) and pneumonia (6%) with pembro+PBO. Patients treated with pembro+CC-486 vs pembro+PBO experienced a higher rate of pembro dose interruptions (29% vs 16%) and discontinuations (20% vs 10%), and a higher rate of CC-486 or PBO dose interruptions (61% vs 24%) and discontinuations (33% vs 12%). Gastrointestinal events, asthenia/fatigue, and elevated transaminase levels were the most common TEAEs leading to discontinuations.

      Conclusion:
      The addition of CC-486 to pembro did not improve the primary endpoint of PFS compared with pembro+PBO. PD-L1 expression did not appear to be predictive of CC-486 treatment efficacy. The increase in TEAEs in the combination arm, particularly gastrointestinal (nausea and vomiting), which are known to be associated with CC-486, may have influenced treatment exposure.

      Efficacy Endpoints Pembro + CC-486 n = 51 Pembro + PBO n = 49
      Overall
      PFS, median, months 3.1 4.0
      ORR, n (%) 10 (19.6) 7 (14.3)
      By PD-L1 Level at Baseline n = 45 n = 44
      PFS, median, months ≥ 50% ≥ 1%-49% 0% 5.5 1.6 3.6 8.0 1.4 3.9
      ORR, % ≥ 50% ≥ 1%-49% 0% 37.5 20.0 18.5 37.5 0.0 7.1


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    MA 05 - Immuno-Oncology: Novel Biomarker Candidates (ID 658)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      MA 05.03 - The Early Monitoring of Derived Neutrophil-To Lymphocyte Ratio (dNLR) Could Be a Surrogate Marker of Benefit of Immunotherapy in NSCLC  (ID 10147)

      15:45 - 17:30  |  Author(s): Benjamin Besse

      • Abstract
      • Presentation
      • Slides

      Background:
      Baseline high derived NLR (dNLR>3, neutrophils/(leucocytes-neutrophils) ratio) has recently correlated with no benefit to immune checkpoint inhibitors (ICI) in advanced NSCLC, but the dynamic monitoring of dNLR has not been assessed in this population.

      Method:
      dNLR at baseline, at 2[nd] cycle and at progressive disease were retrospectively collected in advanced NSCLC patients treated with ICI from November 2012 to April 2017, in a multicentric cohort (N= 292) from 4 European centers. The primary endpoint was overall survival (OS), and secondary endpoints were progression free survival (PFS), response rate (RR) and disease control rate (DCR).

      Result:
      Out of 292 patients (67%) were males, 264 (92%) smokers and 239 (83%) with PS ≤1, with median age 64 years; 153 (52%) had adenocarcinoma and 114 (30%) squamous; 44 (15%) were KRASmut, 11 (4%) EGFRmut and 3 (1%) ALK positive. PDL1 was ≥ 1% by immunohistochemistry in 67 (76%), negative in 21 (24%) and unknown in 204 patients. The median of prior lines was 1 (0-10). The median follow-up was 12 months (m) [11-14]. The median PFS and OS were 4m [3-5] and 11m [9-15]. Baseline dNLR was>3 in 106 patients (36%) and at 2[nd] cycle in 90 patients (32%). dNLR>3 at baseline and at 2[nd] cycle were associated with poor PFS (p<0.0001 and p=0.0008, respectively), poor OS (both p<0.0001) and progressive disease (p=0.002 and p=0.005, respectively). At 2[nd] cycle of ICI, the dNLR status (> high or ≤ 3 low) changed in 63 patients: in 38 (14%) dNLR decreased; in 25 (9%) dNLR increased. According to the dNLR monitoring (combining dNLR at baseline et at 2[nd] cycle), the median OS was 17m (95%CI 13-NA) when dNLR remained low (n=153), 10m (95%CI 7-NA) when dNLR changed (n=64) and 4m (95%CI 3-7) when dNLR remained high (dNLR>3, n=64, p<0.0001).The dNLR monitoring was also associated with PFS (p=0.002), RR and DCR (p=0.003 and p=0.013, respectively).

      Conclusion:
      Monitoring dNLR at baseline and at 2[nd] cycle could be a routinely tool to early assess benefit to ICI in NSCLC patients on treatment. The dNLR monitoring showed a strong correlation with OS and PFS. Modification of dNLR between baseline and 2[nd] cycle impacts outcomes in NSCLC patients treated with ICI.

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    MA 10 - Immunotherapy I (ID 664)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      MA 10.11 - Hyperprogressive Disease (HPD) Is Frequent in Non-Small Cell Lung Cancer (NSCLC) Patients (Pts) Treated with Anti PD1/PD-L1 Agents (IO) (ID 10222)

      11:00 - 12:30  |  Author(s): Benjamin Besse

      • Abstract
      • Presentation
      • Slides

      Background:
      Using Tumor Growth Rate (TGR), HPD was identified in 9% of 131 advanced cancer pts, treated with IO in a single institution (Champiat et al. 2017). In this study, we explored HPD in a large, multicenter cohort of advanced NSCLC pts treated with IO.

      Method:
      We performed a retrospective analysis of consecutive NSCLC pts treated with IO, in 8 institutions, between November 2012 and April 2017. Eligibility criteria required, for each patient: 2 CT scans performed before starting IO and one during IO, an interval between two CT scans ≥2 weeks or 3 months (m) and presence of target lesions. CT scans were centrally assessed according to RECIST 1.1 criteria. We calculated TGR before IO (TGR pre-IO) and during IO (TGR IO); patients were defined HPD if they had progression disease (PD) at first evaluation during IO and a ≥ 2-fold increase in the TGR IO compared to TGR pre-IO. Median overall survival (mOS) was estimated using Kaplan-Meier method for the total population and HPD pts.

      Result:
      Among 419 eligible pts, 86 were excluded for inadequate intervals between CT scans. Among 333 evaluable pts, 63% were male, 46% ≥65 years, 43% smokers; 12% had PS ≥ 2, 65% adenocarcinoma, 45% ≥3 metastatic sites, 22% KRAS mutation, 4% EGFR mutation, 1% ALK rearrangement; 21% had PD-L1 positive status, 10% negative, 69% unknown, >90% received single agent PD-1 inhibitor in ≥ 2 line. Response rate (RR) to IO was 18%, median follow up was 12 m [10-14]. 33% of pts had TGR IO ≥1 (not regressing tumors), 25% had TGR IO ≥ 2-fold TGR pre-IO and 54 pts (16%) had HPD. 15 pts (4%) had confirmed pseudoprogression, 3 were initially qualified as HPD. Compared to not-HPD, HPD pts had more frequently ≥ 3 metastatic sites at baseline (59% vs 43% p=0,02) and more new lung lesions during IO (34% vs 17% p=0,007). PD-L1 negative status was more common among HPD pts but the association was borderline significant (53% vs 28% p=0,05). Age, clinical, molecular characteristics, RR to treatment before IO, baseline tumor burden, liver or brain new lesions during IO were not different according to HPD status. mOS was 13 m [10-17] in the total population, 5 m [3-8] in HPD pts.

      Conclusion:
      HPD occurred in 16% of advanced NSCLC pts treated with IO and was associated with plurimetastatic disease and appearance of new lung lesions. Further work is needed to characterize HPD prognostic value.

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    MA 11 - Emerging Diagnostic/Biomarkers in NSCLC (ID 668)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Advanced NSCLC
    • Presentations: 1
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      MA 11.01 - Liquid Biopsies for Monitoring BRAF Mutation (V600E) in Advanced BRAF (V600E) Non-Small Cell Lung Cancer (NSCLC) (ID 10232)

      11:00 - 12:30  |  Author(s): Benjamin Besse

      • Abstract
      • Presentation
      • Slides

      Background:
      Circulating tumor DNA (ctDNA) has been shown beneficial in monitoring EGFR mutations in blood, especially for the detection of resistance mutations, like T790M in NSCLC patients. However, the role of BRAF (V600E) ctDNA for monitoring the patient’s response has not been studied yet. The aim of this study was to determine the clinical relevance of BRAF (V600E) ctDNA for monitoring the response to BRAF inhibitors in a prospective cohort of advanced NSCLC BRAF (V600E) patients.

      Method:
      We prospectively enrolled advanced NSCLC patients with BRAF (V600E) treated with BRAF +/- MEK inhibitors in our institution. A blood sample was collected at different time points, including at baseline, during treatment and at progressive disease. ctDNA BRAF analysis was performed using the Inivata InVision platform (enhanced tagged-amplicon next-generation sequencing (eTAM-Seq).

      Result:
      Between June 2016 and June 2017, 14 patients have been included. Eight patients (57%) were females, 9 (64%) non-smokers, with a median age of 63 years (35-70). All the patients had adenocarcinoma and BRAF (V600E) mutation in tissue analysis. Thirteen patients (93%) had stage IV at diagnosis, 7 patients (50%) with bone, 6 (43%) pleural and 4 (29%) lung metastasis. The median of lines of treatment received was 2 (1-4). Thirteen patients (93%) received BRAF + MEK inhibitor and 1 patient (14%) BRAF inhibitor, with an objective response rate of 64% (1 complete, 8 partial response) and disease control rate of 86%. BRAF mutation detection was tested under treatment in 12 patients (86%). Longitudinal analysis was performed from the serial sampling in 6 patients to date: 4 patients (67%) were ctDNA positive for BRAF (V600E) at time of progression, with a range of allelic frequency of 0.11-6.16%. BRAF mutation was not detectable in patients with objective response (2/6, 33%) at time of sample collection(s). Additional BRAF (V600E) NSCLC patient samples are being analyzed.

      Conclusion:
      Liquid biopsy for monitoring BRAF (V600E) using ctDNA appears to be feasible and useful in advanced NSCLC patients. Updated longitudinal results for the complete patient cohort will be presented at the meeting.

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    MS 01 - Clinical Development of Novel Agents (ID 523)

    • Event: WCLC 2017
    • Type: Mini Symposium
    • Track: Clinical Design, Statistics and Clinical Trials
    • Presentations: 1
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      MS 01.01 - Expansion Cohorts in Phase I Trials: Non Controlled Phase II or Translational Science? (ID 7640)

      11:00 - 12:30  |  Presenting Author(s): Benjamin Besse

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    OA 03 - Mediastinal and Esophageal Tumor: Insight and New Treatment (ID 654)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      OA 03.01 - Prevalence of Autoimmune Diseases in Thymic Epithelial Tumors (TET) Insights from RYTHMIC (ID 8745)

      11:00 - 12:30  |  Author(s): Benjamin Besse

      • Abstract
      • Presentation
      • Slides

      Background:
      TET have been associated with autoimmune disorders (AID) in up to 30 % of patients. However, there have been wide variations in the reported prevalence of TET associated disorders based mostly on small single center series. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French network mandated to systematically discuss every case of TET. Using our database, we aimed to describe the prevalence of AID in a large French population with TET.

      Method:
      RYTHMIC database prospectively includes all consecutive patients with a diagnosis of TET discussed in our national tumor board. We calculated the prevalence and described epidemiologic, clinical and pathological characteristics of patients with TET’s related autoimmune diseases.

      Result:
      From January 2012 to May 2017, 1693 patients were included in the registry. Of these, 200 patients (11.8%) had autoimmune disorder. The mean age at diagnosis of TET was 54 years old and 52% were male. 149 had myasthenia gravis (75.3%), 15 Good syndrome (7.6%), 14 pure red cell aplasia (7.1%), 12 systemic erythematous lupus (6.1%) and 12 thyroiditis (6.1%). Some patients (14.5%) eventually developed more than 1 AID. Diagnosis of AID was mostly done at the same time of TET diagnosis (54.6%) but some patient had their AID diagnosed before (19.8%) or during follow up (13.4%). Masaoka Koga stages were overall well balanced with 16.5% stage III, 16% stage IIb, 13.5% stage I, 13% stage IIa and IV. Histologic subtype distribution was in order of frequency; B2 (37%), AB (14.5%), B3 (14%), B1 (10.5%), thymic carcinoma (4.5 %) and A (4%).

      Conclusion:
      In our registry of TET, the prevalence of autoimmune diseases was 11.8% and most diagnosis were established at the same time as TET. The extent of disease, measured by Masaoka Koga staging, does not seem correlated.

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    OA 05 - Next Generation TKI (ID 657)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Advanced NSCLC
    • Presentations: 1
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      OA 05.06 - Phase 2 Study of Lorlatinib in Patients with Advanced ALK<sup>+</sup>/ROS1<sup>+</sup> Non-Small-Cell Lung Cancer (ID 8573)

      15:45 - 17:30  |  Author(s): Benjamin Besse

      • Abstract
      • Presentation
      • Slides

      Background:
      Lorlatinib, a selective, potent, brain-penetrant ALK/ROS1 TKI, is active against most known ALK kinase domain mutations. In phase 1 of this ongoing study (NCT01970865), lorlatinib displayed robust clinical activity among patients with ALK[+]/ROS1[+] non-small-cell lung cancer (NSCLC), most of whom were heavily pretreated and had CNS metastases. Phase 2 evaluated efficacy (overall and intracranial), according to prior treatment, and safety at the recommended phase 2 dose (100 mg QD).

      Method:
      Patients with NSCLC ± asymptomatic CNS metastases enrolled in 6 cohorts (EXP1–5, ALK[+]; EXP6, ROS1[+]). The primary endpoint was objective response rate (ORR) and intracranial ORR by independent central review. Safety, patient-reported outcomes and molecular profiling were also assessed.

      Result:
      As of 15-March-2017, 227 ALK[+] patients were evaluated for ORR (Table), including 140 with CNS involvement who were evaluated for intracranial ORR.

      Confirmed ORR Confirmed IC-ORR
      N n (%) N n (%)
      ALK[+] cohorts
      EXP1 (treatment-naïve, no prior ALK-TKIs or CT) 30 27 (90) 8 6 (75)
      EXP2 (prior crizotinib only) 27 20 (74) 17 10 (59)
      EXP3 (1 prior ALK TKI ± CT) 59 30 (51) 32 20 (63)
      EXP3A (prior crizotinib + CT) 32 21 (66) 20 15 (75)
      EXP3B (any 1 other ALK TKI ± CT) 27 9 (33) 12 5 (42)
      EXP4 (2 prior ALK TKIs ± CT) 65 27 (42) 45 25 (56)
      EXP5 (3 prior ALK TKIs ± CT) 46 16 (35) 38 (15 (39)
      CT, chemotherapy; IC, intracranial.
      Of 219 ALK+ patients analyzed for ALK kinase domain mutations at baseline, 46/219 (21%) had ≥1 mutation detected in circulating free DNA; most derived treatment benefit with an ORR of (27/46) 59%. Across all cohorts (N=275), the most common treatment-related adverse events (AEs) and grade 3/4 treatment-related AEs were hypercholesterolemia (81%/16%) and hypertriglyceridemia (60%/16%); 30% and 22% of patients had treatment-related AEs associated with dose interruptions and reductions, respectively. No treatment-related deaths occurred; 7 patients (3%) had treatment-related AEs leading to treatment discontinuation. 157/275 (57%) patients remained on treatment at data cutoff. Most patients reported stable/improved global quality of life (40%/43%).

      Conclusion:
      Lorlatinib showed clinically meaningful activity, including substantial intracranial efficacy, among ALK[+]/ROS1[+] patients who were either treatment-naïve or failed ≥1 prior ALK TKI. Overall lorlatinib was well tolerated and when needed, AEs were managed by dose delay/reduction or standard medical therapy.

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    OA 17 - Immunotherapy II (ID 683)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      OA 17.05 - IFCT-1502 CLINIVO: Real-Life Experience with Nivolumab in 600 Patients (Pts) with Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 9371)

      14:30 - 16:15  |  Author(s): Benjamin Besse

      • Abstract
      • Presentation
      • Slides

      Background:
      Nivolumab is a standard option for second‐line treatment in pts with advanced NSCLC. Real‐life data are lacking regarding the efficacy of nivolumab and post‐nivolumab treatment.

      Method:
      This analysis included the first 600 consecutive pts with stage IIIB/IV NSCLC who received ≥1 dose of nivolumab 3mg/kg q2w through the French EAP from 01/2015 for Squamous ﴾Sq﴿ and 06/2015 for Non‐Sq NSCLC, until 08/2015.

      Result:
      Median age was 64 yo, there were 409 ﴾68%﴿ men, 521 ﴾87%﴿ smokers, 478 ﴾80%﴿ PS0/1 pts, 230 ﴾38%﴿ Sq and 370 ﴾62%﴿ Non‐Sq NSCLC, 130 ﴾22%﴿ pts with brain metastases. Nivolumab was administered as 2nd/3rd/≥4th‐line for 26%/33%/41% pts, respectively. Best response was PR/SD/PD for 17%/30%/37% of patients, respectively, with 16% not assessable. Toxicities occurred in 187 ﴾31%﴿ pts, including 10% grade ≥3 events. After a median follow‐up of 22.1 ﴾95% CI 21.6‐22.6﴿ months, median PFS and OS from the initiation of nivolumab were 2.1 ﴾95%CI 1.9‐2.3﴿ and 9.5 ﴾95%CI 8.4‐10.8﴿ months, respectively. In the 92 pts with PS2 at initiation of nivolumab, PR/SD rates were 7%/28%; median OS was 3.6 (95%CI 2.7-5.2) months. A total of 130 pts had brain metastases at initiation of nivolumab: PR/SD rates were 12%/25%; median OS was 6.6 (95%CI 3.8-8.3) months. Post‐nivolumab treatment was administered to 262 ﴾44%﴿ pts, and mostly consisted of gemcitabine ﴾19%﴿, docetaxel ﴾18%﴿, paclitaxel ﴾14%﴿, erlotinib ﴾12%﴿, vinorelbine ﴾9%﴿, platin‐based doublet ﴾8%﴿, or pemetrexed ﴾8%﴿. Access to post‐nivolumab treatment was higher in PS0/1 vs. PS2 pts ﴾48% vs. 23%, p<0.001﴿, but was not different according to histology or treatment line or disease control with nivolumab. Best response to post‐nivolumab treatment was PR/SD/PD for 15%/42%/42% of pts, respectively. In the whole cohort, median post‐nivolumab OS was 4.0 ﴾95%CI 2.8‐4.6﴿ months, and was significantly higher in case of PR to nivolumab ﴾HR=0.38; 95%CI 0.23‐0.64; p<0.001﴿, and if subsequent treatment was delivered ﴾HR=0.30; 95%CI 0.24‐0.38; p<0.001﴿; median post‐nivolumab OS in pts receiving post‐nivolumab treatment was 7.5 ﴾95%CI 6.8‐8.7﴿ months, and did not differ based on histology or treatment line.

      Conclusion:
      Efficacy and safety of nivolumab was in line with available data. Post‐nivolumab treatment may be delivered in many pts, including pts with PS2 and brain metastases, with favorable impact on response and OS. Data on the whole cohort of 900 pts enrolled in the EAP will be presented.

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    P1.03 - Chemotherapy/Targeted Therapy (ID 689)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P1.03-013 - Monitoring of ALK Fusions and Mutations in Advanced ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients (ID 10208)

      09:30 - 16:00  |  Author(s): Benjamin Besse

      • Abstract

      Background:
      Co-isolated exosomal RNA and cfDNA from plasma can be used for detection of genomic alteration such as EML4-ALK fusion RNA and ALK resistance mutations in NSCLC patients. The clinical utility of this liquid biopsy for response monitoring is under investigation. The aim of this study was to evaluate liquid biopsy as tool for monitoring response to treatment in a prospective cohort of ALK-positive NSCLC patients.

      Method:
      Consecutive ALK positive NSCLC patients treated with systemic therapies in our institution were enrolled. After informed consent, blood samples were prospectively collected for longitudinal analysis during treatment and at progression. Exosomal RNA and cfDNA co-isolated from plasma was used for detection of EML4-ALK fusion RNAs by the qPCR-based ExoDx Lung(ALK)™-test as well as for analysis of ALK-resistance mutations by ExoDx NGS sequencing.

      Result:
      From Aug 2016 to date, 23 patients were enrolled in the study, 14 (61%) were females, 15 (65%) non-smokers, median age of 50 years (23-76). All patients had adenocarcinoma and were tissue positive for ALK by immunohistochemistry 14 (61%) and/or FISH 16 (70%). Nineteen patients (83%) had stage IV disease at diagnosis, with brain involvement in 7 patients (37%), bone in 11 (48%) and liver in 2 (11%). The median number of ALK inhibitors received was 2 (0-4). Twenty-one patients (91%) received ALK inhibitors (5 crizotinib, 3 ceritinib, 13 next-generation inhibitors) and 2 chemotherapy, with an objective response rate of 48%. Five out of 8 patients (63%) that were treatment naïve (baseline) or progressive disease (PD) at the time of collection, were positive for EML4-ALK by liquid biopsy, 1 of 4 samples (25%) at baseline, and 4 of 4 samples (100%) at PD, were positive by liquid biopsy. EML4-ALK variant 1 was detected in two (40%) and variant 3 in three patients (60%). All 26 samples collected during objective response or stable disease (100%) were negative for EML4-ALK by liquid biopsy. The ALK resistance mutation panel was performed on 2 samples from patients with PD, and both were detected positive for ALK resistance mutations, L1196M (variant 1) and G1202R (variant 3), respectively.

      Conclusion:
      The monitoring of ALK fusions on exosomal RNA by liquid biopsy is applicable in the clinic and closely correlated to disease control. ALK mutations detection using liquid biopsy can be an accurate tool for assessing the resistance to ALK inhibitors. Updated results from up to 30 patients will be available for the final presentation.

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    P1.08 - Locally Advanced NSCLC (ID 694)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      P1.08-009 - Neutrophilia as Prognostic Biomarker in Locally Advanced Stage III Lung Cancer (ID 8920)

      09:30 - 16:00  |  Author(s): Benjamin Besse

      • Abstract

      Background:
      To study the prognostic value of leucocyte disorders in two retrospective cohorts of stage III Non-Small Cell Lung Cancer (NSCLC) patients, and to compare their accuracy with established prognostic markers.

      Method:
      Clinical records of consecutive previously untreated NSCLC patients in our Institution between June 2001 and September 2016 for stage III NSCLC were collected. The prognostic value of pretreatment leucocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophil count exceeding 10 and 7 G/L, respectively.

      Result:
      We identified 238 patients (145 patients prospectively registered through MSN study (NCT02105168) with 136 additional patients), displaying baseline leukocytosis or neutrophilia in 39% and 40% respectively. Most were diagnosed with adenocarcinoma (48%), and stage IIIB NSCLC (58%). 3-year actuarial overall survival (OS) and progression-free survival (PFS) were 35% and 27% respectively. Local relapses were reported in 100 patients (42%), and distant metastases in 132 patients (55%). In multivariate analysis, leukocytosis, neutrophilia, and induction chemotherapy regimen based on carboplatin/paclitaxel were associated with worse OS and PFS (p<0.05). Neutrophilia independently decreased Locoregional Control (LRC) (HR=2.5, p<0.001) and Distant Metastasis Control (DMC) (HR=2.1, p<0.001). Neutrophilia was significantly associated with worse brain metastasis control (p=0.004), mostly in adenocarcinoma patients (p<0.001). Figure 1



      Conclusion:
      In stage III NSCLC patients, treated with concurrent cisplatin-based chemoradiation, baseline leukocytosis and neutrophilia predict OS, PFS, LRC, and DMC. In addition with previously available markers, this independent cost-effective biomarker could help to stratify stage III NSCLC population with more accuracy.

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    P2.01 - Advanced NSCLC (ID 618)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.01-038 - Determinants of Frailty and Treatment Toxicity in Non-Small Cell Lung Cancer Patient (ID 9566)

      09:00 - 16:00  |  Author(s): Benjamin Besse

      • Abstract
      • Slides

      Background:
      Platinum-based chemotherapy remains a first line treatment for advanced non-small-cell lung cancers (NSCLC). Despite better individualization of treatment, some patients will seek frequent medical attention because of cancer-related complications or treatment toxicity. This can negatively impact patient’s quality of life and health care resources. This study aimed to identify biological and clinical factors predictive of frailty and treatment toxicity among NSCLC patients eligible for first-line platinum-based chemotherapy.

      Method:
      Using our institutional medical charts, we retrospectively extracted data on stage III and IV NSCLC patients diagnosed between December 2011 and November 2015 who had received a first-line platinum based chemotherapy. The primary outcome is defined as any unplanned emergency visit and/or unplanned hospitalization for cancer or treatment related complications. Using multivariate logistic regression model with step by step method, we defined baseline biological and clinical determinants associated with the primary outcome.

      Result:

      Table 1. First Multivariate Analysis
      Variable OR 95% CI
      Age ≥ 62 Years-old 1.61 0.70 - 3.68
      Adenocarcinoma - Squamous Cell Carcinoma - NSCLC other 1 2.43 0.50 0.61- 9.61 1.45 – 1.74
      Performance scale ≥ 1 1.35 0.57 – 3.18
      Number of metastasis ≥ 2 1.36 0.58 – 3.18
      Pleural metastasis 2.04 0.53 – 7.86
      Weight loss ≥10% or ≥3 kg 1.00 0.41 – 2.43
      ≥ 3 prescription drugs per day 0.98 0.42 – 2.28
      Current smoker - Former Smoker - Never smoker 1 0.56 1.10 0.24 – 1.30 0.24 – 5.11
      Neutrophils count ≥ 7500/ mm[3] 1.57 0.70 – 3.54
      Lymphocytes count ≤ 1000/ mm[3] 1.04 0.34 – 3.22
      Albumin ≤ 35 g/L 2.70 0.93 – 7.69
      LDH ≥ 247 U/L 0.93 0.37 – 2.30
      We included 227 patients. Mean age was 60 years old, 65% were male, 46% current smokers, 10% PS 2-3 and 74% had adenocarcinoma histology. 20,7% patients had locally advanced disease (Stage III) treated by chemoradiation and 78,4% had metastatic disease treated by exclusive chemotherapy. Median overall survival (OS) was 15 months and PFS 6 months. Overall, 55 % (122/227) met the primary outcome. There were 14 variables (Table 1) included in the first multivariate analysis before computer based step by step approach. In the final model (not shown), albumin level <35 g/L (OR 2.24 95% IC 1.14- 4.38, p= 0.02) was an independent predictor of the primary outcome. There was also a trend for squamous cell carcinoma subtype (OR 2.27 95% IC 0.872- 5.914, p= 0.09).

      Conclusion:
      Low albumin level is a determinant of frailty in patients eligible for platinum-based chemotherapy. Early intervention in these subgroups could benefit patient’s quality of life and health care expenses. (Medicoeconomic analysis will be presented).

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    P2.07 - Immunology and Immunotherapy (ID 708)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 2
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      P2.07-005 - Impact of Baseline Leptomeningeal and Brain Metastases on Immunotherapy Outcomes in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 7958)

      09:30 - 16:00  |  Author(s): Benjamin Besse

      • Abstract

      Background:
      Central nervous system (CNS) involvement is frequent in NSCLC patients and associated with poor prognosis. However, its impact on immune checkpoints inhibitors’ (ICI) outcomes remains unknown.

      Method:
      We retrospectively collected the clinical and imaging data of a cohort of 271 patients treated with ICI in our institute from Nov. 2012 to April 2017. We analyzed overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR), and CNS outcomes using brain CT scan and/or MRI. Both body and CNS outcomes were assessed prospectively by investigators.

      Result:
      With a median follow up of 17 months (95% IC 15-21), 259 patients were evaluated, 48 (19%) had CNS involvement before immunotherapy; 225 were (87%) smokers, 78% had PS ≤1, with median age of 63.1; 166 (64%) had adenocarcinoma; 67 (26%) were KRASmut, 14 (5%) EGFRmut and 3 (1%) ALK positive. PDL1 was ≥1% by immunohistochemistry in 68 (28%), negative in 28 (11%) and unknown in 163 patients. Median number of prior lines was 1 (0-11). The global ORR was 20%. The median OS was 8 months (95% IC 6-11). No difference was observed in OS between CNS+ vs. CNS- population (p= 0.09). The global ORR was 18% vs. 20%, in CNS+ and CNS- patients, respectively (p=1). To date, CNS–relative data are available for 36 patients: n= 32 brain metastasis, n=7 meningeal carcinomatosis, including 4 cytological positivity, n=2 leptomeningeal and n=1 medullar metastasis. Thirty-one patients (86%) had brain target lesions and 15 were evaluable for CNS outcome (CNS progressive disease (PD) before starting ICI and/or no brain radiation therapy (RT) in the previous 6 months. Median interval between consecutive CNS assessments was 2 months. Twenty-two had CNS PD before immunotherapy: 41% (9/22) received radiation therapy (RT) the month before immunotherapy (4 whole brain RT, 5 stereotactic). No differences were observed according to prior RT, with a median OS of 10 months (95%IC 2-NR) vs. 8 months. (95%IC 5-NR) for prior vs. no prior RT (p=0.79). The median OS for the 7 patients with meningeal carcinomatosis was 2 months (0 to 20). The CNS ORR was 27% (4/15, 3 partial, 1 complete response) and CNS DCR was 60% (9/15). One CNS pseudo progression (7%) and one dissociated brain response (7%) were observed.

      Conclusion:
      CNS involvement did not seem to be associated with a negative impact on immunotherapy outcomes in advanced NSCLC patients. Final analysis of the entire cohort will be presented.

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      P2.07-060 - Response Assessment and Subgroups Analysis According to the Lung Immune Prognostic Index (LIPI) for Immunotherapy in Advanced NSCLC Patients (ID 10179)

      09:30 - 16:00  |  Author(s): Benjamin Besse

      • Abstract

      Background:
      LIPI is a score that combine dNLR (neutrophils/(leucocytes-neutrophils) and lactate dehydrogenase (LDH) and correlate with prognosis of NSCLC patients treated with immune checkpoint inhibitors (ICI). We report the predictive role of LIPI on response and in various subgroups of patients.

      Method:
      Baseline dNLR and LDH were retrospectively collected in 431 patients treated with ICI from Nov. 2012 to Jan. 2017, from 8 European centers. LIPI delineates 3 groups: good (dNLR<3+LDH3 or LDH>ULN), poor (dNLR>3+LDH>ULN). Response rate (RR) and disease control rate (DCR) were assessed according to the investigator’s criteria. The subgroup analysis was performed according to the age, histology, performance status (PS) and PD-L1 status by immunohistochemistry (positivity if ≥ 1% on tumor cells).

      Result:
      With a median follow-up of 12.8 months (m.) [95%CI 11.9-14], 431 patients were included. Baseline characteristics are summarized in table 1. The median overall survival (OS) and progression-free survival (PFS) were 10.5m. [95%CI 9.5-13] and 3.9m. [3-4.4], respectively. The median OS was 4.8m. vs. 10 m. vs. 16.5m., and median PFS was 2m. vs. 3.1m. vs. 5m. for the poor, intermediate and good LIPI groups, respectively (both p<0.0001). LIPI was correlated with response rate (p<0.0001). In multivariate analysis, the intermediate and poor group were associated with progressive disease, with an OR of 2.20 [CI95% 1.26-3.84] p=0.005) and an OR of 3.04 [CI95% 1.46-6.36] p=0.003), respectively. LIPI was correlated with OS, regardless the age (<70 years (p<0.0001) vs. older (p=0.0006) and the histology non-squamous (p<0.0001) vs. squamous (p=0.02). In PS 0-1 and in smoker population, LIPI correlated with OS (both p<0.0001), but not in PS ≥2 (12%) and non-smokers (8%). LIPI was correlated with OS for positivity (p=0.01) and unknown PD-L1 (p=0.0001), but not negativity.

      LIPI 0 Good (N=162, 37%) LIPI 1 Intermediate (N=206, 48%) LIPI 2 Poor (N= 63, 15%) All population cohort N = 431 (%)
      Sex
      Male 102 (63) 131 (64) 42 (67) 275 (64)
      Age at diagnosis
      Median (years, range) 62 (36;86) 63 (29;86) 62 (39;84) 62 (29;86)
      Smoking status
      Non-smoker 13 (8) 18 (9) 5 (8) 36 (8)
      Former 80 (49) 115 (56) 46 (73) 241 (56)
      Current 67 (42) 69 (33) 11 (17) 147 (34)
      Unknown 2 4 1 7
      Histology
      Non-squamous 111 (69) 132 (64) 41 (65) 284 (66)
      Squamous 51 (31) 74 (36) 22 (35) 147 (34)
      Molecular alteration
      EGFR mutation 3 (2) 13 (6) 3 (5) 19 (4)
      ALK rearrangement 2 (1) 2 (1) 1 (2) 5 (1)
      KRAS mutation 34 (21) 31 (15) 8 (13) 73 (17)
      PDL1 status
      Negative 16 (36) 14 (25) 1 (5) 31 (25)
      Positive 28 (64) 43 (75) 20 (95) 91 (75)
      Unknown 118 149 42 337
      Performance Status
      0 51 (32) 45 (22) 10 (16) 106 (25)
      1 96 (60) 132 (64) 42 (67) 270 (63)
      ≥ 2 12 (8) 28 (14) 11 (17) 51 (12)
      Stage at diagnosis
      IIIb 18 (11) 33 (16) 14 (22) 65 (15)
      IV 101 (62) 135 (66) 38 (60) 274 (64)
      Metastases sites
      Median (Range) 2 (0;6) 2 (0;7) 2 (1;7) 2 (0-7)
      Bone 43 (27) 58 (28) 20 (32) 121 (28)
      Liver 28 (17) 39 (19) 16 (25) 83 (19)
      Brain 22 (14) 19 (9) 9 (14) 50 (12)
      Immunotherapy
      PD1 inhibitor 133 (82) 167 (81) 48 (76) 348 (81)
      PDL1 inhibitor 19 (12) 34 (17) 12 (19) 65 (15)
      PDL1 inhibitor- CTLA4 inhibitor 10 (6) 5 (2) 3 (5) 18 (4)
      Immunotherapy line
      Median (Range) 2 (1;11) 2 (1;12) 2 (1;8) 2 (1-12)
      Response rate
      Complete response (CR) 6 (4) 3 (1) 0 (0) 8 (2)
      Partial response (PR) 42 (26) 53 (26) 18 (28) 113 (26)
      Stable disease (SD) 66 (41) 59 (29) 8 (13) 133 (31)
      Progression 40 (25) 81 (39) 33 (52) 154 (36)
      NA 8 10 4 25
      Dissociated response 14 (9) 15 (7) 2 (3) 31 (7)


      Conclusion:
      Baseline LIPI predicts response to ICI, and was correlated with OS regardless of age and histology.