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Jaafar Bennouna



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    MA 03 - Chemotherapy (ID 651)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Advanced NSCLC
    • Presentations: 2
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      MA 03.01 - Nab-Paclitaxel ± CC-486 as Second-Line Treatment of Advanced NSCLC: Results from the ABOUND.2L+ Study (ID 8676)

      11:00 - 12:30  |  Author(s): Jaafar Bennouna

      • Abstract
      • Presentation
      • Slides

      Background:
      CC-486 (oral azacitidine) is an epigenetic modifier with potential effect as a priming agent for chemotherapy in patients with NSCLC. Outcomes of nab-paclitaxel+CC-486 vs nab-paclitaxel as second-line treatment of advanced NSCLC are reported.

      Method:
      Patients with advanced nonsquamous NSCLC and no more than 1 prior chemotherapy line (including platinum doublet combination) were randomized (1:1) to nab-paclitaxel 100 mg/m[2] d8, 15 + CC-486 200 mg qd d1-14 or nab-paclitaxel 100 mg/m[2] d1, 8, both administered q3w until progressive disease/unacceptable toxicity. Primary endpoint was PFS. Secondary endpoints: DCR, ORR, OS, and safety. QoL, an exploratory endpoint, was assessed on d1 of each cycle.

      Result:
      The nab-paclitaxel+CC-486 arm was discontinued in October 2016 due to demonstrated futility vs nab-paclitaxel monotherapy upon completion of a protocol-specified interim analysis. Overall, 161 patients were randomized (nab-paclitaxel+CC-486, 81; nab-paclitaxel, 80). Baseline characteristics were balanced between arms. The median number of cycles was 4 for each arm, and the median nab-paclitaxel cumulative dose was 600 mg/m[2] and 800 mg/m[2] in the nab-paclitaxel+CC-486 and nab-paclitaxel arms, respectively. Rates of grade 3/4 (G3/4) treatment-emergent AEs were 59.5% and 54.4% for the combination and monotherapy arms, respectively. The most frequent hematologic G3/4 AEs were neutropenia (16.5% vs 10.1%) and anemia (1.3% vs 7.6%). G3/4 peripheral neuropathy was reported in 2.5% and 7.6% of patients, respectively. The addition of CC-486 to nab-paclitaxel did not improve ORR, DCR, PFS, or OS (Table). When assessed by Lung Cancer Symptom Scale, nab-paclitaxel monotherapy was associated with improvement in the global QoL, average symptom burden index, and lung cancer symptoms except for hemoptysis.

      Conclusion:
      The addition of CC-486 to nab-paclitaxel did not clinically benefit patients with previously treated NSCLC. However, single-agent nab-paclitaxel appears to be a promising therapy based on safety, efficacy, and QoL data. Updated efficacy and safety data will be presented. NCT02250326

      nab-Paclitaxel + CC-486 n = 81 nab-Paclitaxel n = 80
      Median PFS, months 3.2 4.2
      HR (95% CI) 1.3 (0.9 - 2.0)
      1-year PFS, % 4.1 18.3
      Median OS, months 8.4 12.7
      HR (95% CI) 1.4 (0.88 - 2.31)
      1-year OS, % 39.2 54.3
      ORR, n (%)[a] 11 (13.6) 11 (13.8)
      Response rate ratio (95% CI) 0.99 (0.45 - 2.15)
      CR PR SD PD DCR (≥ SD) 0 11 (13.6) 41 (50.6) 22 (27.2) 52 (64.2) 0 11 (13.8) 43 (53.8) 19 (23.8) 54 (67.5)
      CR, complete response; DCR, disease control rate; HR, hazard ratio; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease. [a] Response rate was based on the intent-to-treat population; however, 14 patients did not have a response assessment.


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      MA 03.05 - Bevacizumab Combined with Chemotherapy for Patients with Advanced NSCLC and Brain Metastasis. A French Cohort Study (ID 8188)

      11:00 - 12:30  |  Presenting Author(s): Jaafar Bennouna

      • Abstract
      • Presentation
      • Slides

      Background:
      Although brain metastases (BM) are a very common and clinically challenging for NSCLC progression, there are few prospective studies addressing the safety and efficacy of bevacizumab in combination with chemotherapy in patients with BM. This study aimed to describe the characteristics of patients receiving bevacizumab in combination with first-line metastatic chemotherapy for advanced NSCLC (aNSCLC), with BM or not, in routine clinical practice.

      Method:
      For this French non-interventional, prospective, and multicenter study, data were collected every 3 months over an 18-month period, from bevacizumab initiation. End points were progression-free survival (PFS), overall survival (OS), treatment use, and safety.

      Result:
      Amongst the 407 aNSCLC patients analyzed, the 84 patients (21%) with BM at bevacizumab initiation had poorer general health than patients without BM (ECOG 2: 16% versus 11%). All except for 2 patients received bevacizumab (7.5 or 5 mg/kg/3 weeks in 99% of patients) in combination with doublet chemotherapy. After a median follow-up of 10.8 months (range: 0.2-34.1), median PFS and OS were not significantly different between patients with or without BM. BM was not found as PFS prognosis factor in multivariate analysis (HR=1.03; 95% CI=[0.79; 1.33], p=0.85). At least one serious adverse event (SAE) was reported in 30% of aNSCLC patients with BM (n=25) and in 32% of patients without BM (n=106); 13% (n=11) and 12% (n=40) of patients experienced at least one bevacizumab-related SAE, respectively. Three patients in each group died from bevacizumab-related events.

      aNSCLC patients with brain metastasis - N=84 (months, [CI 95%]) aNSCLC patients without brain metastasis - N=423 (months, [CI 95%]) Logrank test p value
      Median PFS 6.5 [5.7; 8.1] 6.9 [5.9; 7.6] 0.57
      Median OS 14.5 [10.0; -] 12.5 [10.1; 14.7] 0.33


      Conclusion:
      In this study, no differences were observed between advanced NSCLC patients with and without brain metastasis in terms of clinical benefit (survival and safety) from first-line chemotherapy combined with bevacizumab. Nature, severity and outcome of AEs were consistent with the known safety profile of bevazicumab.

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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 10.02 - Nab-Paclitaxel + Durvalumab as Second- or Third-Line Treatment of Advanced NSCLC: Results from ABOUND.2L+ (ID 8682)

      11:00 - 12:30  |  Author(s): Jaafar Bennouna

      • Abstract
      • Presentation
      • Slides

      Background:
      Chemotherapy may enhance immunotherapeutic effects by causing tumor antigen release, which primes the immune system to kill tumor cells. Early clinical data on nab-paclitaxel + carboplatin in combination with immune checkpoint inhibitors (ICI) demonstrated promising activity without compounding toxicities in patients with non-small cell lung cancer (NSCLC). ABOUND.2L+ evaluated nab-paclitaxel–based regimens in previously treated patients with advanced NSCLC. Here we report the efficacy and safety of nab-paclitaxel + durvalumab as second/third-line treatment.

      Method:
      Patients with advanced NSCLC were assigned to receive second/third-line (immunotherapy allowed in prior line, including platinum doublet combination) nab-paclitaxel 100 mg/m[2] on days 1 and 8 + durvalumab 1125 mg on day 15, in 21-day cycles, administered until unacceptable toxicity/progression per immune-related RECIST v1.1. Primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety.

      Result:
      Seventy-nine patients were enrolled. Median age was 63 years, 68% of patients were male, 23% had Eastern Cooperative Oncology Group performance status of 0, and 70% had nonsquamous NSCLC; 11% of patients received prior ICIs. Median PFS (Table) and OS were 4.5 (3.4-5.8) months and NE (7.3-NE). ORR was 27% (1 complete response) and DCR was 71%. Grade 3/4 treatment-emergent adverse events of special interest occurring in ≥ 5% of patients included neutropenia (6%) and dyspnea (5%); grade 3/4 peripheral neuropathy and anemia each occurred in 4% of patients. Median treatment duration was 24 weeks; median number of treatment cycles was 7. For nab-paclitaxel and durvalumab, median dose intensities were 59.05 mg/m[2]/week and 326.61 mg/week, respectively; median percentages of per-protocol dose were 88.58% and 87.10%.

      Conclusion:
      The combination of durvalumab with nab-paclitaxel demonstrated antitumor activity with manageable toxicity in the second/third-line setting. Further details will be presented. NCT02250326

      Nab-P Durva Median PFS (range), months
      Overall (n = 79) 4.5 (3.4-5.8)
      ICI pretreated (n = 9)[a] ICI naive (n = 69)[a] 6.9 (1.4-NE) 4.4 (3.0-5.7)
      Squamous (n = 23)[a] Nonsquamous (n = 55)[a] 5.9 (3.0-7.8) 4.2 (2.9-5.7)
      ICI, immune checkpoint inhibitor; NE, not estimable; PFS, progression-free survival. [a] Data pending for 1 patient.


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    P2.04 - Clinical Design, Statistics and Clinical Trials (ID 705)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Clinical Design, Statistics and Clinical Trials
    • Presentations: 1
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      P2.04-010 - Afatinib in Combination with Pembrolizumab in Patients with Stage IIIB/IV Squamous Cell Carcinoma (SCC) of the Lung (ID 9425)

      09:30 - 16:00  |  Author(s): Jaafar Bennouna

      • Abstract
      • Slides

      Background:
      Afatinib has demonstrated progression-free survival (PFS) and overall survival (OS) improvements in patients with squamous cell carcinoma (SCC) of the lung; pembrolizumab also showed encouraging PFS/OS in lung SCC. Afatinib is a selective and irreversible ErbB family blocker that effectively inhibits signaling from all homo- and heterodimers formed by ErbB family members EGFR (ErbB1), HER2 (ErbB2), ErbB3, and ErbB4. Pembrolizumab is a humanized immunoglobulin G4 (IgG4) monoclonal antibody with high affinity and potent receptor-blocking activity for the programmed cell death 1 (PD-1) receptor. Concurrent inhibition of PD-1 and EGFR pathways represents a rational and promising approach for EGFR-driven tumors such as SCC of the lung, to increase the rate and duration of response, and delay the development of resistance, as single-agent efficacy can be moderate and more treatment options are needed. This trial assesses the efficacy and safety of afatinib in combination with pembrolizumab in patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) who progressed during or after first-line platinum-based treatment.

      Method:
      Trial design: Study 1200.283 (NCT03157089. LUX-Lung IO / Keynote 497) is a phase II, open-label, non-randomized single-arm study. Eligible patients have locally advanced or metastatic squamous NSCLC and have progressed during/after first-line platinum-based chemotherapy. Patients must have adequate organ function and ECOG PS 0/1. Prior treatment with immune checkpoint inhibitors or EGFR targeted therapy is prohibited. A safety run-in will be performed using afatinib once daily (starting dose 40 mg) in combination with pembrolizumab, (200 mg fixed dose once every 3 weeks, administered intravenously) to assess the safety profile and confirm the recommended Phase II dose (RP2D). In the main part of the trial, afatinib at the RP2D, in combination with pembrolizumab, may be continued for a maximum of 35 cycles (~2 years). After study completion, further therapy will be decided by the investigator and may include afatinib. Dose reduction of afatinib to 30 mg or 20 mg will be permitted in the case of adverse events. The primary endpoint is investigator assessed objective response (complete response [CR] or partial response [PR] according to RECIST v1.1). Secondary/further endpoints are disease control (CR, PR, or stable disease), duration of objective response, PFS, OS, tumor shrinkage, RP2D, and pharmacokinetics. Exploratory biomarker analysis will also be performed. This study will be conducted in the US, Spain, France, Korea, and Turkey, and will open for enrollment in September 2017; target enrollment is 50-60 patients.

      Result:
      Not applicable

      Conclusion:
      Not applicable

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