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Santiago Ponce-Aix



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    FP07 - Pathology (ID 109)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP07.06 - Lung Immune Prognostic Index (LIPI) in Advanced NSCLC Patients Treated with Immunotherapy, Chemotherapy and both Combined Upfront. (ID 823)

      00:00 - 00:00  |  Author(s): Santiago Ponce-Aix

      • Abstract
      • Presentation
      • Slides

      Introduction

      The Lung Immune Prognostic Index (LIPI) that combines the neutrophils/[leucocytes minus neutrophils] ratio (dNLR) and lactate dehydrogenase (LDH), is associated with outcomes in pretreated advanced NSCLC patients receiving single agent immune checkpoint inhibitors (ICI). However, its role in first line treatment of advanced NSCLC patients has not been explored yet. We assessed the value of baseline LIPI in the first line setting, for ICI-monotherapy, ICI-combination or platinum-based chemotherapy alone (CT).

      Methods

      We retrospectively collected data of patients treated with first-line ICI between 2016 and 2019 as single agent if PD-L1 ≥50% (ICI-cohort), or in combination with a CTLA4-inhibitor (ICI+ICI cohort), or with chemotherapy (ICI+CT cohort), from 18 centers worldwide. A control cohort of patients treated with platinum-based CT (CT-cohort) was also collected between 2011 and 2019 from 2 centers. Baseline LIPI was calculated as previously reported and correlated with overall survival (OS) and progression-free survival (PFS) in each treatment cohort.

      Results

      Overall, 930 patients were enrolled, 561 in the ICI-cohort, 186 in the combo ICI+CT, 55 in the ICI+ICI and 128 in the CT-cohort. Median (m) follow-up was 12.5 months. In the whole cohort, median age was 66 years, 70% male, 80% had non-squamous histology, and 84% had PS ≤1. Based on LIPI (available for 792 patients): 305 (38%) were considered good, 331 (42%) intermediate and 156 (20%) poor group.

      Treatment outcomes according to LIPI scores are depicted in Table 1. The LIPI poor population had significantly worse OS compared with other LIPI groups, in the whole cohort (P<0.001) as well as in the ICI monotherapy and combo ICI+CT cohorts (both P<0.0001); and in the CT cohort (P=0.004). In term of PFS, we observed correlation between LIPI groups and outcomes in the whole cohort (P<0.001) and in the ICI- monotherapy cohort (P=0.008); however, no differences were observed in the cohorts of patients receiving chemotherapy regimens, alone (P=0.08) or combined with ICI (P=0.08). The analysis by PD-L1 expression in 756 patients with available data will be presented in the Congress.

      Table 1: Median OS and PFS according to LIPI subgroups. NR = non reached.

      Outcomes

      LIPI

      subgroups

      Overall cohort

      N= 925

      ICI-cohort

      N=558

      ICI + CT-cohort

      N= 185

      ICI + ICI cohort

      N= 55

      CT-cohort

      N=127

      Median OS

      (95% CI)

      All

      16.3 (14.7-18.8)

      21.0 (17.1-NR)

      24.7 (16.9-27.1)

      20.5 (14.1-NR)

      9.79 (8.3-14.4)

      LIPI good, 38.5%

      19.8 (17.2-25.7)

      NR (NR-NR)

      25.7 (25.6-NR)

      33.6 (14.7-NR)

      14.42 (8.9-17.9)

      LIPI interm, 41.8%

      15.8 (14.3-20.3)

      21.2 (17.1-NR)

      20.3 (12.8-NR)

      14.6 (5.5-NR)

      9.30 (7.0-14.5)

      LIPI poor, 19.7%

      6.96 (5.6-12.5)

      8.5 (3.4-13.7)

      6.1 (4.9-NR)

      14.1 (10.3-NR)

      6.1 (5.0-NR)

      Global LogRank P value

      <0.0001

      <0.0001

      <0.0001

      0.4

      0.004

      Overall cohort

      N= 909

      ICI-cohort

      N=543

      ICI + CT-cohort

      N= 185

      ICI + ICI cohort

      N= 54

      CT-cohort

      N=127

      Median PFS

      (95% CI)

      All

      6.5 (5.9-7.1)

      6.3 (5.0-7.6)

      8.9 (6.80-10.9)

      7.2 (5.7-30.6)

      5.7 (5.3-6.4)

      LIPI good, 38.7%

      7.0 (5.9-8.5)

      6.4 (4.5-10.8)

      9.8 (7.8-13.0)

      9.2 (5.7-NR)

      6.0 (5.3-7.8)

      LIPI interm, 41.6%

      6.6 (6.1-7.6)

      6.6 (5.6-8.1)

      10.4 (6.4-12.4)

      5.5 (2.5-NR)

      6.1 (4.3-7.6)

      LIPI poor, 19.7%

      3.6 (3.1-5.6)

      3.3 (1.9-6.7)

      4.5 (2.8-8.2)

      7.1 (2.56- NR)

      3.7 (3.4-NR)

      Global LogRank P value

      <0.0001

      0.008

      0.08

      0.4

      0.08

      Conclusion

      Pretreatment LIPI was prognostic in untreated advanced NSCLC patients regardless of the type of therapy. However, LIPI was associated with PFS only in patients receiving ICI-monotherapy, with no statistically significant differences in CT-containing cohorts (alone or combined with ICI). This value of LIPI to guide treatment selection should be further explored in prospective studies.

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    OA11 - A Symphony of Progress (ID 229)

    • Event: WCLC 2020
    • Type: Oral
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
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      OA11.04 - Lurbinectedin With Irinotecan in Relapsed Small Cell Lung Cancer. Results From the Expansion Stage of a Phase I-II Trial (ID 3132)

      15:30 - 16:30  |  Presenting Author(s): Santiago Ponce-Aix

      • Abstract
      • Presentation
      • Slides

      Introduction

      Lurbinectedin is a novel anti-cancer agent that exerts antitumor activity through inhibition of trans-activated transcription and modulation of the tumor microenvironment. In June 2020, the US FDA granted accelerated approval to lurbinectedin (ZepzelcaTM) for the treatment of adult patients (pts) with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy based on the results of a phase II study (Trigo et al. Lancet Oncol 2020). Preclinical evidence of synergism was observed for lurbinectedin in combination with irinotecan.

      Methods

      Antitumor activity and the safety of lurbinectedin in combination with irinotecan in SCLC were evaluated in this phase I-II trial. Data are presented here for advanced SCLC (pts) with no more than 2 prior lines of chemotherapy and ECOG performance status (PS) score of 0-1 treated at the recommended dose (RD).

      Results

      21 pts were treated at the RD (lurbinectedin 2 mg/m2 Day 1 + irinotecan 75 mg/m2 Days 1 and 8 every three weeks + prophylactic G-CSF); all were evaluable for safety and efficacy. Baseline characteristics were: males/females, 48%/52%; median age, 61 years (52-74); ECOG PS score 0/1, 24%/76%; chemotherapy-free interval (CTFI) ≥90 days/<90 days, 62%/38%; number of prior lines, 1 (62%), 2 (38%); prior immunotherapy (19%); liver metastases 48%; CNS involvement 24%. At cut-off (12 August 2020), 11 patients were still on treatment.

      All patients

      (n=21)

      CTFI

      Setting

      90 days (n=13)

      <90 days (n=8)

      2nd line (n=13)

      3rd line (n=8)

      Median number of cycles

      (range)

      7

      (1-16)

      9

      (3-16)

      3

      (1-7)

      7

      (3-16)

      7

      (1-13)

      Overall Response Rate (PR)

      62%

      69%

      50%

      77%

      37%

      Clinical Benefit Rate (PR+SD>4m)

      71%

      85%

      50%

      77%

      63%

      Disease Control Rate (PR+SD)

      90%

      100%

      75%

      100%

      75%

      Median DOR (m)

      (95% CI)

      5.7+

      (2.8-n.r.)

      6.7+

      (3.0-n.r.)

      3.2+

      (2.8-3.7)

      6.7+

      (3.0-n.r.)

      3.0+

      (2.8-n.r.)

      Median PFS (m)

      (95% CI)

      6.2+

      (4.1-n.r.)

      8.5+

      (4.3-n.r.)

      3.7+

      (0.7-5.0)

      8.1+

      (3.3-n.r.)

      4.3+

      (0.7-n.r.)

      Median follow-up: 8.7 months

      + patients ongoing; CTFI, chemotherapy-free interval; DOR, duration of response; m, months; n.r. not reached; PFS, progression-free survival; PR, partial response; SD, stable disease.

      Adverse events (AEs) included: grade (G) 4 neutropenia in 6 pts (28.6%); febrile neutropenia in 2 pts (9.5%); no G4 anemia or G4 thrombocytopenia. Severe non-hematological toxicities were G3 only and consisted mainly of fatigue in 4 pts (19.0%), diarrhea in 3 pts (14.3%), and vomiting in 1 pt (4.5%). No deaths or discontinuations were reported due to treatment-related AEs.

      Conclusion

      The combination of lurbinectedin and irinotecan demonstrated efficacy in SCLC after failure of first-line therapy, including remarkable activity in pts with resistant disease (CTFI <90 days) and in the 3rd line setting. Toxicity was transient and manageable, and consisted mainly of hematological abnormalities, fatigue and diarrhea. Further development of this combination is warranted in pts with SCLC. Updated results of this cohort will be presented.

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    P18 - Locoregional and Oligometastatic Disease - Misc. Topics (ID 128)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Locoregional and Oligometastatic Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P18.05 - Immunotherapy Beyond First-Line in NSCLC, Still An Option. (ID 3220)

      00:00 - 00:00  |  Author(s): Santiago Ponce-Aix

      • Abstract
      • Slides

      Introduction

      Atezolizumab and nivolumab are approved in patients with advanced previously treated non-small cell lung cancers (NSCLC) irrespective of programmed death-ligand 1 (PD-L1) expression, while pembrolizumab is only approved if PD-L1 ≥1%. At present, immunotherapy alone or in combination with chemotherapy is the treatment of choice for first-line NSCLC, however treatment with anti-PD-1/PD-L1 agents should be reconsidered after progression to chemotherapy in patients which did not receive immunotherapy at first time.

      Methods

      In this retrospective analysis, we analysed the impact of immunotherapy in second and subsequent lines in terms of median progression-free survival (mPFS) and median overall survival (mOS) in patients with advanced NSCLC treated in University Hospital 12 Octubre from October, 2015 to March, 2020.

      Results

      We identified 87 patients with NSCLC treated with immunotherapy in second or posterior lines (42 received nivolumab, 32 atezolizumab and 13 pembrolizumab). 79.32% were men, median age was 67.6 years and 67.8% of them received at least 3 doses of treatment. In the total population, mPFS was 4 months and mOS was 10 months. Significant differences were observed when divided by histology subtypes: mPFS 2 months for adenocarcinoma vs 5 months for squamous (HR: 1.85 [95% CI: 1.08-3.15], p=0.01). Nevertheless, in terms of survival no significant differences were observed, mOS was 9 vs 11 months, respectively (HR: 1.36, [95% CI: 0.73 - 2.53], p=0.29). Among patients with stage III at diagnosis, mPFS and mOS were significantly longer than those with stage IV. mPFS was 7 vs 2 months (HR: 0.53 [95% CI: 0.31–0.90], p=0.009), and mOS was 15 vs 9 months (HR: 0.49, [95% CI: 0.28-0.91], p=0.02). The expression of PD-L1 was not predictive of immunotherapy benefit, although 45% patients were unknown. We also observed a benefit for those patients with ECOG 0-1 compared with ≥2 (mOS: 11 vs 5.5 months; HR: 0.49 [95% CI: 0.23-1.05], p= 0.01).

      mPFS (months)

      mOS (months)

      Histology

      Adenocarcinoma

      2

      HR: 1.85 [95% CI: 1.08-3.15],

      p=0.01).

      9

      HR: 1.36, [95% CI: 0.73-2.53],

      p=0.29).

      Squamous

      5

      11

      Stage

      III

      7

      HR: 0.53 [95% CI: 0.31–0.90], p=0.009

      15

      HR: 0.49, [95% CI: 0.28-0.91], p=0.02

      IV

      2

      9

      ECOG

      0-1

      3

      HR 0.62 (95% CI 0.31 - 1.24)

      P = 0.08

      11

      HR: 0.49 [95% CI: 0.23-1.05], p= 0.01

      ≥2

      2

      5.5

      Conclusion

      Patients with NSCLC not suitable to receive chemoimmunotherapy in first-line setting must be reconsider in second or posterior lines due to the important benefit observed. These results based on our clinical practice seem to be similar to those observed in previous clinical trials.

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    P21 - Locoregional and Oligometastatic Disease - Treatment of Locally Advanced NSCLC (ID 131)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Locoregional and Oligometastatic Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P21.14 - The Promising role of Chemo-Immunotherapy in Non-Small Cell Lung Cancer Neoadjuvant Setting (ID 3551)

      00:00 - 00:00  |  Author(s): Santiago Ponce-Aix

      • Abstract
      • Slides

      Introduction

      Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease which includes patients with different prognosis depending on resectable, potentially resectable or unresectable tumours. Chemo-immunotherapy in neoadjuvant setting is currently under evaluation in clinical trials. We present two case reports of patients who received this therapeutic approach due to tumour unresectability at diagnosis.

      Methods

      Data were collected from electronic history and clinical records. All procedures performed were in accordance with ethical standards of the institutional research Committee and the treatment strategy was approved as compassionate use in both cases.

      Results

      A 56-year old male and a 48-year old female (37 and 45 pack-year history, respectively) presented with two-month history of productive cough and moderate progressive dyspnoea. In Case 1, the 18F-FDG PET/CT showed a 12 cm (diameter greater) necrotic mass (SUVmax 18.43) and non-metabolic ipsilateral pleural effusion (Figure 1A), staging cT4N0M0 (IIIA). On the other hand, a 5.8 cm (diameter greater) right hilar mass (SUVmax 20.25), ipsilateral pleural effusion (SUVmax 6.45) and a right subcarinal suspicious adenopathy were shown in Case 2 (Figure 1C). Bronchoscopic biopsy revealed a primary pulmonary squamous cell carcinoma with PD-L1 expression 90% (22C3) in both cases and they were presented in Multidisciplinary Tumour Board. In Case 1, the mass was considered unresectable and the patient was not eligible for radical chemo-radiotherapy, so systemic therapy was finally decided. Otherwise, pleural effusion cytological assessment was performed several times without showing malignant cells in Case 2 (staging cT3N2Mx) and systemic treatment was started too due to the tumour unresectability. Chemo-immunotherapy combination with carboplatin AUC 5mg/ml/min, paclitaxel 175mg/m2 and pembrolizumab 200mg every three weeks according to the results of KEYNOTE-407 was given in both cases. Favourable response was achieved after four cycles (Case 1, Figure 1B; Case 2, Figure 1D), therefore both cases were discussed again in Multidisciplinary Session in order to reevaluate surgical indication. After mediastinoscopy, Case 1 underwent right pneumonectomy in December 2019 (postoperative staging ypT1cN0M0) and Case 2 underwent middle and lower bilobectomy in June 2019, with major pathological response (MPR). At present, both patients are asymptomatic, with no evidence disease and no antineoplastic treatment.

      figure 1.jpg

      Conclusion

      Radiological response achieved with chemo-immunotherapy allowed a surgical approach in patients with non-resectable tumours at diagnosis. MPR is a surrogate of overall survival in resectable NSCLC, so results of ongoing clinical trials exploring this combination strategy are expected with much interest because they could change the therapeutic paradigm of these patients.

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