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Sara Baglivo



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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
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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): Sara Baglivo

      • 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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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-23 - TP53 Mutations as Mechanisms of Primary and Acquired Resistance to Tyrosine Kinase Inhibitors in Patients With EGFR-Mutated NSCLC  (ID 13954)

      16:45 - 18:00  |  Author(s): Sara Baglivo

      • Abstract
      • Slides

      Background

      Around 80% of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations usually respond to tyrosine kinase inhibitors (TKIs). We previously demonstrated that TP53 mutations are associated with primary resistance to TKIs in patients with EGFR-mutated lung adenocarcinoma (ADC) treated with a first-line TKI. In the present study we investigated whether TP53 mutations are modulated by TKIs, evaluating its status before and after TKI treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Thirty-five patients with EGFR-mutated lung ADC treated with a first-line TKI and who subsequently underwent re-biopsy after disease progression were considered. Tumor tissue was available for evaluation before and after TKI treatment for all patients. EGFR and TP53 mutation analyses were performed by Sanger Sequencing or Next Generation Sequencing methods. The different mutations were evaluated in relation to disease control rate (DCR) [complete response (CR), partial response (PR) or stable disease (SD)] and objective response rate (ORR) (CR, PR).

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 35 patients, 14 (40%) showed a TP53 mutation, 12 in exons 5-8 (5 in exon 5, 2 in exon 6, 2 in exon 7 and 3 in exon 8) and 2 in other exons (1 in exon 2 and 1 in exon 4) of the gene. The group was treated with a first-line TKI and data on response and follow-up were available for 30 patients. Of these, 11 were treated with gefitinib, 11 with erlotinib, 6 with afatinib and 2 with dacomitinib. Overall DCR and ORR were 90% and 77%, respectively. With regard to TP53 mutations, DCR and ORR were 94% and 83%, respectively, in TP53 wt patients, and 83% and 66% in TP53 mutated cases. All 30 patients underwent re-biopsy at progression and 20 (67%) showed T790M mutation in tumor tissue. Of the 10 T790M-negative patients, 5 (50%) had a TP53 mutation which was not present at baseline in 2 cases. Among the patients who were TP53 wild type at baseline, 4 (22%) showed a mutation at disease progression. Data on progression free survival and overall survival are currently being evaluated.

      8eea62084ca7e541d918e823422bd82e Conclusion

      TP53 mutations were associated with a lower response to TKIs in EGFR-mutated patients and may have been acquired during TKI treatment, independently of the T790M mutation.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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