Author of

• 25767

  +

  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

  • 25773

    +

    OA05.05 - Avelumab vs Docetaxel for Previously Treated Advanced NSCLC: Primary Analysis of the Phase 3 JAVELIN Lung 200 Trial (ID 12930)

    14:15 - 14:25  |  Author(s): Aleksandra Szczesna
    • Abstract
    • Presentation
    • Slides

    Background
    

    Avelumab is a human anti–PD-L1 IgG1 monoclonal antibody that is an approved treatment for metastatic Merkel cell carcinoma (various regions) and platinum-treated advanced urothelial carcinoma (US). We report findings from a global, open-label, phase 3 trial of avelumab vs docetaxel in patients with advanced NSCLC after platinum failure (NCT02395172).

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Patients with stage IIIB/IV or recurrent NSCLC with disease progression after platinum doublet therapy were randomized 1:1 to avelumab 10 mg/kg Q2W or docetaxel 75 mg/m² Q3W, stratified by PD-L1 status (PD-L1+/PD-L1−) and histology (squamous/nonsquamous). The primary endpoint was overall survival (OS) in the PD-L1+ population (expression on ≥1% of tumor cells, assessed using the PD-L1 IHC 73-10 assay).

    4c3880bb027f159e801041b1021e88e8 Result
    

    Between April 2015 and February 2017, 792 patients were randomized to receive avelumab or docetaxel, including 264 and 265 with PD-L1+ tumors, respectively; 0.8% vs 7.5% did not receive study treatment. Median follow-up in the avelumab and docetaxel arms was 18.9 and 17.8 months; 15.5% vs 1.5% remained on treatment at data cutoff (November 22, 2017). In the avelumab and docetaxel arms, 39.8% vs 47.5% received subsequent anticancer therapy after discontinuation, including checkpoint inhibitors in 5.7% vs 26.4%, respectively. In the PD-L1+ population, median OS in the avelumab and docetaxel arms was 11.4 vs 10.3 months (hazard ratio [HR], 0.90 [96% CI, 0.72-1.12]; P=0.1627, 1-sided). Pre-planned exploratory analyses based on higher PD-L1 cutoffs showed increased OS with avelumab vs docetaxel, including PD-L1-high (≥80% cutoff, 29% of patients; 17.1 vs 9.3 months; HR, 0.59 [95% CI, 0.42-0.83]; P=.0022, 2-sided) and PD-L1-medium/high (≥50% cutoff, 40% of patients; 13.6 vs 9.2 months; HR, 0.67 [95% CI, 0.51-0.89]; P=0.0052, 2-sided) subgroups. In the PD-L1+ population (≥1% cutoff), ORR was 18.9% vs 11.7% (odds ratio, 1.76 [95% CI, 1.08-2.86]; P=0.0105, 1-sided); median duration of response was not reached with avelumab (95% CI, 9.9-not estimable [NE]) vs 6.9 months with docetaxel (95% CI, 3.5-NE). Overall rates of treatment-related adverse events (AEs) were lower with avelumab than docetaxel, including all grades (63.9% vs 85.8%) and grade ≥3 (9.9% vs 49.3%). Immune-related AEs occurred in 16.5% of avelumab-treated patients (grade ≥3 in 2.8%).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Avelumab showed increasing clinical activity in patients who had platinum-treated NSCLC with higher tumor PD-L1 expression; however, the trial did not meet its primary objective of improving OS vs docetaxel in PD-L1+ tumors (≥1% cutoff). OS findings may have been confounded by subsequent checkpoint inhibitor therapy in the docetaxel arm.

    6f8b794f3246b0c1e1780bb4d4d5dc53

    Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

    Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

• 25088

  +

  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

  • 26171

    +

    PL02.07 - IMpower 133: Primary PFS, OS and Safety in a PH1/3 Study of 1L Atezolizumab + Carboplatin + Etoposide in Extensive-Stage SCLC (ID 12892)

    09:00 - 09:10  |  Author(s): Aleksandra Szczesna
    • Abstract
    • Presentation
    • Slides

    Background
    

    First-line (1L) standard-of-care treatment for extensive-stage small cell lung cancer (ES-SCLC) is platinum (carboplatin or cisplatin) with etoposide. Despite high initial response rates, there has been limited progress in the last two decades and outcomes remain poor with a median overall survival (OS) of ~10 months. IMpower133 (NCT02763579), a global Phase 1/3, double-blind, randomized, placebo-controlled trial evaluated efficacy and safety of adding atezolizumab, a humanized monoclonal anti–PD-L1 antibody, or placebo to 1L carboplatin and etoposide in ES-SCLC.

    Patients with measurable (RECIST v1.1) ES-SCLC, ECOG performance status 0 or 1, who had not received prior systemic treatment for ES-SCLC were enrolled. PD-L1 immunohistochemical testing was not required. Patients were randomized 1:1 to receive four 21-day cycles of carboplatin (AUC 5 mg/mL/min IV, Day 1) plus etoposide (100 mg/m² IV, Days 1-3) with either atezolizumab (1200 mg IV, Day 1) or placebo, followed by maintenance therapy with atezolizumab or placebo until intolerable toxicity or progressive disease per RECIST v1.1. Patients meeting predefined criteria could receive treatment beyond progression. Co-primary endpoints were OS and investigator-assessed progression-free survival (PFS). Adverse events (AEs) were graded per NCI-CTCAE v4.0. Blood-based tumor mutation burden (bTMB) was assessed using prespecified cutoffs of ≥16 vs. <16 and ≥10 vs. <10 mutations/Mb.

    In total, 201 patients were randomized to the atezolizumab group, and 202 to the placebo group. Median follow-up was 13.9 months. Median OS was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio [HR] 0.70 [95% confidence interval (CI): 0.54, 0.91; P=0.0069]). Median PFS was 5.2 months and 4.3 months, respectively (HR 0.77 [95% CI: 0.62, 0.96; P=0.017]). OS and PFS benefits were consistent across key patient subgroups. Investigator-assessed confirmed objective response rates were 60.2% and 64.4% in the atezolizumab and placebo groups, respectively; median duration of response, 4.2 and 3.9 months. Exploratory analyses showed OS survival benefits in subgroups above and below prespecified bTMB cutoffs. Grade 3-4 treatment-related AEs were reported in 56.6% vs. 56.1% patients in atezolizumab vs. placebo groups, respectively; serious treatment-related AEs occurred in 22.7% and 18.9% patients, respectively.

    Addition of atezolizumab to carboplatin and etoposide provided a significant improvement in OS and PFS in 1L ES-SCLC in an all-comer patient population. No unexpected safety signals were identified. Atezolizumab plus carboplatin and etoposide may represent a new standard regimen for patients with untreated ES-SCLC.

    a9ded1e5ce5d75814730bb4caaf49419

    Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

    Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.