Author of

• 25899

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  MA10 - Considerations in Immunotherapy / Real World (ID 911)

  • Event: WCLC 2018
  • Type: Mini Oral Abstract Session
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 10:30 - 12:00, Room 105

  • 25980

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    MA10.06 - Impact of Immune-Related Adverse Events on Survival in Patients with Advanced Non-Small Cell Lung Cancer Treated with Nivolumab (ID 13039)

    11:05 - 11:10  |  Author(s): Andrea De Giglio
    • Abstract
    • Presentation
    • Slides

    Background
    

    Anti PD1 and anti PD-L1 monoclonal antibodies represent the standard of care for platinum-pretreated advanced non-small cell lung cancer (NSCLC) patients, having shown to prolong survival compared to chemotherapy in second-line setting in phase III clinical trials. Patients treated with these drugs not infrequently experience immune-related adverse events (irAEs), which we hypothesize might reflect antitumor response. In this study we investigated whether the development of irAEs was associated with nivolumab efficacy in patients with advanced NSCLC.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We conducted a multicenter retrospective study of patients with advanced NSCLC treated with nivolumab between October 2013 and September 2017. IrAEs were defined as AEs having immunological basis that required intensive monitoring and interventions. We evaluated nivolumab efficacy according to the development of irAEs.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Among 195 patients (median [range] age, 63 [30-40] years; 128 men [65.6%], 67 women [34.4%]), irAEs were observed in 85 patients (43.6%), including 15 patients (7.6%) with grade 3 or 4 events. Median PFS was 5.7 months in patients with irAEs compared to 2 months of those without irAEs (P < 0.0001). Median OS was 17.8 months compared to 4.04 months of no-irAEs group (P < 0.0001). The survival benefit of irAEs was consistent also in 12- and 6-weeks landmark analysis. Patients who developed ≥ 2 irAEs (n: 37) had a significantly longer median PFS and OS compared to those with one AE (n: 48) or none (n: 110) (PFS: 8.5 months vs. 4.6 vs. 2, P < 0.0001; OS: 26.8 months vs. 11.9 vs. 4, P < 0.0001). Multivariable analysis revealed that irAEs were positively associated with survival outcome, with hazard ratios of 0.48 (95%CI, 0.34-0.77; P < 0.0001) for PFS and 0.38 (95%CI, 0.26-0.56; P < 0.0001) for OS.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    This is the largest study conducted to date aimed to evaluate whether the development of irAEs is predictive of nivolumab efficacy in pre-treated NSCLC patients. In this study we confirmed that the development of irAEs was a strong predictor of survival outcomes in NSCLC patients who had received nivolumab in ≥ 2 line setting. This data was consistent in the 12- and 6-weeks landmark analysis, suggesting that an early onset of irAEs might be predictive of durable clinical benefit in NSCLC patients treated with nivolumab. Moreover, patients who experienced ≥ 2 irAEs had a more pronounced survival benefit compared to those with 1 irAE. Further studies are required to investigate the molecular mechanisms underlying this association.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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• 25935

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  P1.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 947)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall

  • 26669

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    P1.15-01 - Radiotherapy (RT) and Nivolumab in Non-Small-Cell Lung Cancer (NSCLC): A Multicenter Real-Life Experience (ID 12194)

    16:45 - 18:00  |  Author(s): Andrea De Giglio
    • Abstract
    • Slides

    Background
    

    The combination of RT and programmed death 1 (PD-1) inhibitors seems augment antitumor immune responses. The aim of this study was to assess the outcome of patients (pts) with NSCLC previously undergone to RT before receiving nivolumab, a PD-1 inhibitor

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We conducted an observational, retrospective analysis of 95 consecutive pts with advanced NSCLC who received any RT within 10 months prior nivolumab, as clinically indicated, at seven Italian institutions. Tumor response to treatment was defined according to RECIST criteria version 1.1. Median overall survival (OS) and the 95% confidence interval (CI) were estimated with the Kaplan -Meier method.

    4c3880bb027f159e801041b1021e88e8 Result
    

    95 pts (median age 66 years [range 41-82]; male:63.2%) with advanced NSCLC (adenocarcinoma [adc]:66.3%; squamous cells [sqc]:33.7%) were treated with nivolumab after RT. Median OS was 11.9 months (mo) [95% CI, 6.6-17.2 (adc: 13.0 mo [95% CI,6.7-19.3], sqc 10.5 mo [95%CI,3.9-17.1]). Median progression free survival (PFS) was 6.3mo [95% CI,4.6-8.0] (adc: 6.4 mo[ 95% CI,4.5-8.3]; sqc: 3.7 mo [95% CI,0.0-8.3]). A better performance status (PS) according to ECOG scale was associated with an improved OS (PS 0[38 pts]: 17.9 mo [95% CI,12.3-23.5; p<0.0001]; PS1[50pts]: 6.9 mo [95%CI,3.2-10.6]; PS2[7pts]: 4.4 mo [95% CI,3.9-4.9]). Median OS in 70 pts who received ≤ 1 previous systemic therapy was 13.0 mo [95% CI, 10.4-15.6] and in 25 pts who received ≥2 prior lines was 7.4 mo [95% CI, 1.8-12.9]. Median OS in 69 pts (72.6%) receiving extracranical RT was 12.0 mo [95%CI,6.6-17.4] and in 26 (27.4%) pts with cranial RT was 11.7 mo [95%CI,NE]; p=0.31. Median OS was shorter in 36 pts receiving bone-RT [7.3 mo; 95% CI, (0-15.3)] when compared with 59 pts receiving extra-bone RT [14.4 mo; 95% CI, (10.3-18.5); p=0.007]. Median OS in 68 pts aged < 70 years was 11.9 mo [95% CI,6.5-17.3] and in 27 elderly (≥ 70 years) was 12.0 mo [95% CI, 3.8-20.1]. 1 (1.0%) complete response, 25(26.3%) partial response, 28(29.5%) stable disease and 41 (43.2%) progressive disease have been observed.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    This study shows that combining irradiation with nivolumab for the treatment of advanced NSCLC leads to improve OS and promote tumor control both locally and distantly.This potentially synergistic effect was comparable among pts regardless previous lines of therapy, histology, type of RT and age.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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