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M. Reck



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    Best of Posters - IASLC Selection - Part 2 (ID 263)

    • Event: WCLC 2013
    • Type: Exhibit Showcase Session
    • Track:
    • Presentations: 1
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      P1.11-018 - An Open-Label, Multicenter, Randomized, Phase II Study of Cisplatin and Pemetrexed With or Without Cixutumumab (IMC-A12) as First-Line Therapy in Patients With Advanced Nonsquamous Non-Small Cell Lung Cancer (ID 1449)

      09:55 - 10:00  |  Author(s): M. Reck

      • Abstract
      • Slides

      Background
      Pemetrexed combined with cisplatin is an approved first-line treatment regimen for patients with advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC). New targets are needed to further improve first-line therapy outcomes. Cixutumumab, a fully human IgG1 monoclonal antibody, specifically blocks the insulin-like growth factor-type 1 receptor, inhibiting its activation and signal transduction. Early studies have reported clinical efficacy and safety with cixutumumab. However, the clinical benefit of adding cixutumumab to conventional chemotherapy is yet to be established. This study assessed whether pemetrexed and cisplatin combined with cixutumumab was superior to pemetrexed and cisplatin as first-line therapy.

      Methods
      This open-label, multicenter, randomized, phase II study (N=172) enrolled patients ≥18 years of age with stage IV nonsquamous NSCLC and ECOG performance status 0–1. Patients were randomized (1:1) to receive cixutumumab 20 mg/kg combined with pemetrexed 500 mg/m[2] and cisplatin 75 mg/m[2] (cixutumumab arm; n=87) or pemetrexed and cisplatin (control arm; n=85) every 21 days up to 6 cycles of induction therapy. Patients eligible for maintenance therapy received pemetrexed and cixutumumab (cixutumumab arm) or pemetrexed (control arm). The primary endpoint was progression-free survival (PFS) based on radiographic assessments. To test for superiority (1-sided significance level 20%; study power 80%), a median PFS of 7.16 months in the cixutumumab arm (HR cixutumumab/control=0.74) was expected. Secondary endpoints included objective response rate (ORR), duration of response, and overall survival (OS). Adverse events (AEs) were assessed using CTCAE version 4.0. Between-arm comparisons of unstratified data are presented.

      Results
      Baseline patient and disease characteristics were similar between arms in the intent-to-treat population. The mean age of the population was 59 years (range, 32 to 83). Dose intensity for all treatments was ≥90% during both study phases. Median PFS was 5.45 months (95% CI, 3.88–6.05) vs. 5.22 months (95% CI, 4.24–6.74) in the cixutumumab and control arms, respectively (HR 1.15, 95% CI, 0.81–1.61; P=0.440). ORR did not significantly differ between treatments (37.9% cixutumumab vs. 30.6% control; P=0.338); however, the median duration of response was numerically greater in the cixutumumab arm (4.9 months; 95% CI, 4.17–6.28) than in the control arm (3.91 months; 95% CI, 2.92–6.41), although differences were not significant (HR 0.74, 95% CI, 0.40–1.38; P=0.340). Median OS was 10.68 months (95% CI, 8.74–not evaluable) in cixutumumab vs. 10.38 months (95% CI, 7.43–14.39) in control patients (HR 0.85, 95% CI, 0.56–1.30; P=0.450). Common AEs reported in ≥10% of patients were nausea, hyperglycemia, fatigue, vomiting, and anemia. A greater proportion of patients in the cixutumumab arm (74.1%) had grade 3/4 AEs than patients in the control arm (61.7%). Grade 3/4 hyperglycemia occurred at a higher rate in the cixutumumab arm than the control arm (11.8% vs. 1.2%). One possibly cixutumumab-related death occurred during the study.

      Conclusion
      Superior PFS was not achieved in nonsquamous NSCLC patients when cixutumumab was added to the pemetrexed and cisplatin treatment regimen, and no significant improvement for any other endpoint was observed. Pemetrexed combined with cisplatin and cixutumumab was tolerable, with no new safety concerns reported.

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    O16 - NSCLC - Targeted Therapies III (ID 115)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      O16.01 - Impact of tumor burden on the overall survival analysis of the LUME-Lung 1 study: a randomized, double-blind phase 3 trial of nintedanib (BIBF 1120) + docetaxel in NSCLC patients progressing after first-line chemotherapy (ID 3284)

      10:30 - 10:40  |  Author(s): M. Reck

      • Abstract
      • Presentation
      • Slides

      Background
      Nintedanib is an orally available potent anti-angiogenic agent inhibiting the isoforms of VEGFR, PDGFR and FGFR. LUME-Lung 1 is a placebo-controlled phase 3 trial of nintedanib + docetaxel in second-line NSCLC patients.

      Methods
      Patients with stage IIIB/IV or recurrent NSCLC after failure of first-line chemotherapy were stratified by histology, ECOG PS, prior bevacizumab and brain metastases, and were randomised to nintedanib 200 mg bid + docetaxel 75 mg/m[2] q21d (n=655), or placebo + docetaxel (n=659). The primary endpoint was centrally reviewed PFS after 714 events. The key secondary endpoint was OS after 1,121 events. Predefined sensitivity analyses used baseline sum of longest diameters of target lesions (SLD) and stratification factors, as covariates in the Cox model.

      Results
      The study met its primary endpoint demonstrating a statistically significant improvement in PFS that translated into a 21% reduction in the risk of progression in patients treated with the combination of nintedanib + docetaxel vs placebo + docetaxel (HR 0.79; CI: 0.68, 0.92; p=0.0019; median 3.4 vs 2.7 months), regardless of histology (adenocarcinoma HR 0.77, CI: 0.62, 0.96; p=0.0193; squamous HR 0.77, CI: 0.62, 0.96; p=0.0200). OS was significantly prolonged in adenocarcinoma patients treated with the combination of nintedanib + docetaxel vs placebo + docetaxel (HR 0.83; CI: 0.70, 0.99; p=0.0359; median 12.6 vs 10.3 months) but not in squamous cell carcinoma patients (HR 1.01; CI: 0.85, 1.21; p=0.8908; median 8.6 vs 8.7 months). The intent-to-treat (ITT) analysis of OS in all study patients showed a 1-month improvement that did not reach statistical significance (HR 0.94; CI 0.83, 1.05; p=0.272; median 10.1 vs 9.1 months). When adjusted for SLD, however, a significant OS benefit was seen for the ITT population (HR 0.88; CI: 0.78, 0.99; p=0.0365). Further analyses showed that the impact of SLD was reflected in the squamous cell carcinoma population (HR 0.92; CI: 0.77, 1.10; p=0.3649), with the greatest impact observed for squamous cell carcinoma patients with a large SLD. An impact of SLD was also seen in adenocarcinoma patients but to a lesser extent (HR 0.81; CI:0.69, 0.97; p=0.0186), as compared with the squamous cell carcinoma population. The most common AEs reported for the ITT population were diarrhea (any: 42.3 vs 21.8%; Gr ≥3: 6.6 vs 2.6%) and ALT elevations (any: 28.5 vs 8.4%; Gr ≥3: 7.8 vs 0.9%). Incidence of CTCAE Gr ≥3 AEs was 71.3 vs 64.3%. Withdrawals due to AEs (22.7 vs 21.7%) were similar in both arms, as were Gr ≥3 hypertension, bleeding or thrombosis.

      Conclusion
      Nintedanib + docetaxel significantly reduced the risk of progression in NSCLC patients independent of histology. Adjustment for tumor burden, as represented by the SLD, led to a significant reduction in the risk of death. AEs were generally manageable with dose reductions and symptomatic treatment.

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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.10-036 - Afatinib in Platinum- and Gefitinib or Erlotinib-pretreated Patients with NSCLC. A single Institution experience in a compassionate-use-program (ID 2124)

      09:30 - 09:30  |  Author(s): M. Reck

      • Abstract

      Background
      Backround and Rationale: The inhibition of the Epidermal Growth Factor Receptor (EGFR) is a treatment option in patients with non-small cell lung cancer (NSCLC). Afatinib is an inhibitor of EGFR as well as the other members of the ErbB family. This compassionate use program was initiated to offer a treatment option for patients after failure of platinum-based chemotherapy and reversible TKI.

      Methods
      Material and Methods: Patients with NSCLC who had had platinum-based chemotherapy and therapy with gefitinib or erlotinib for at least 6 months or who had an activating mutation in the EGFR-gene were eligible to enter this compassionate use program. Patients were given 50 mg (or 40 mg at the investigators´ decision) of afatinib daily until progression or intolerable adverse events. Here we report on our clinical experience at our institution.

      Results
      Results: 18 Patients were enrolled at our center. 6 had an activating mutation, 1 had proven wild type and 11 had an unknown EGFR-status. The median duration of therapy was 2.4 months (range 0.5 to > 19 months). Interestingly, one of the remissions was observed in a patient with proven EGFR wild-type. Most adverse events were EGFR-TKI class-specific and manageable by dose-adaption.

      Conclusion
      Conclusions: Afatinib is an appropriate treatment option for patients who benefitted from treatment with gefitinib or erlotinib.