Virtual Library

Start Your Search

Maximilian Papi



Author of

  • +

    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

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

      P1.01-14 - Immunotherapy (I) for Advanced, Pre-Treated, Non-Squamous NSCLC (APNS-NSCLC). Preliminary Data of a Pooled Analysis (ID 13469)

      16:45 - 18:00  |  Author(s): Maximilian Papi

      • Abstract
      • Slides

      Background

      Background. To assess the role of I for second line treatment of APNS-NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Methods. A pooled analysis of the final data of the CA209057, the KEYNOTE-010 and the OAK trial was performed. Overall Survival (OS) was the primary end point of the trial. The outcomes of patients with PD-L1 expression of 1%-49% (PD-L1 1%-49%), PD-L1 expression <1% (PD-L1<1%) or mutated-EGFR (EGFR+) were analyzed comparing any checkpoint inhibitor with standard chemotherapy. An indirect comparison with network meta-analysis was performed between the different checkpoint inhibitors whenever a significant difference was observed in the pooled analysis. Direct and indirect comparisons were performed using a random effect model.

      4c3880bb027f159e801041b1021e88e8 Result

      Results. The outcome of 1720 patients was analyzed. 313 patients had been treated with Atezolizumab (A), 292 with Nivolumab (N), 270 with Pembrolizumab (P), and 845 with Docetaxel (D). The preliminary results were detailed in the table.

      Legend. CI95%: 95% Confidence Interval; *: Pooled Analysis; **: Network Meta-Analysis.

      OS Hazard Ratio

      CI95%

      A vs D (PD-L1 1%-49%)

      0.571

      0.423-0.771

      P<0.001

      N vs D (PD-L1 1%-49%)

      0.62

      0.467-0.882

      P=0.001

      P vs D (PD-L1 1%-49%)

      0.76

      0.604-0.956

      P=0.019

      I vs D (PD-L1 1%-49%)*

      0.66

      0.555-0.786

      P<0.001

      A vs N (PD-L1 1%-49%)**

      0.921

      0.609-1.392

      P=0.696

      A vs P (PD-L1 1%-49%)**

      0.751

      0.541-1.043

      P=0.087

      N vs P (PD-L1 1%-49%)**

      0.816

      0.597-1.116

      P=0.491

      N vs D (PD-L1<1%)

      0.9

      0.66-1.214

      P=0.491

      A vs D (PD-L1<1%)

      1.04

      0.619-1.747

      P=0.882

      I vs D (PD-L1<1%)*

      0.933

      0.72-1.21

      P=0.601

      P vs D (EGFR+)

      0.88

      0.453-1.71

      P=0.706

      N vs D (EGFR+)

      1.18

      0.693-2.004

      P=0.542

      I vs S (EGFR+)*

      1.052

      0.695-1.594

      P=0.81

      8eea62084ca7e541d918e823422bd82e Conclusion

      Conclusions. Our data seem to confirm the role of I for APNS-NSCLC with PD-L1 1%-49%. On the contrary, not-significant benefits in terms of OS seem to emerge for patients with PD-L1<1% or EGFR+ expression. Likewise, no significant differences seem to emerge from the indirect comparisons between A, N and P for patients with a PD-L1 1%-49% expression. Although all these data need to be analyzed with caution, as expression of indirect comparisons, waiting further conformations from clinical trials they can support clinicians for daily clinical practice.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      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.

  • +

    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
    • +

      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): Maximilian Papi

      • 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

      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.

  • +

    P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P2.13-06 - TP53 Status in Relation to Response to Anti-ALK Agents in Patients with EML4-ALK-Translocated NSCLC (ID 12580)

      16:45 - 18:00  |  Author(s): Maximilian Papi

      • Abstract
      • Slides

      Background

      Patients with non-small-cell lung cancer (NSCLC) carrying the EML4-ALK translocation are responsive to anti-ALK agents, such as crizotinib. However, about 30%-40% of patients show primary resistance to treatment. We previously demonstrated that TP53 mutations are associated with poorer prognosis in EGFR-mutated patients treated with tyrosine-kinase inhibitors. In the present study we analyzed the impact of TP53 mutations on response to anti-ALK treatment in EML4-ALK-translocated NSCLC

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Eighty-three patients with EML4-ALK-translocated NSCLC identified in the Wide Catchment Area of Romagna between 2012 and 2016 were considered. TP53 status was evaluated in 61 patients on the basis of DNA availability. Of these, 28 patients received an anti-ALK agent as second-or-more-line treatment and follow-up data were available. TP53 status was analyzed in relation to disease control rate (DCR): complete response (CR), partial response (PR) or stable disease (SD).

      4c3880bb027f159e801041b1021e88e8 Result

      Overall, TP53 mutations were observed in 14 (23%) patients, 6 (43%) showing a mutation in exon 5, 1 (7%) in exon 6, 3 (21%) in exon 7 and 4 (28%) in exon 8. We found one insertion (7%), one deletion (7%) and 12 point mutations (86%). Of the 28 patients treated with an anti-ALK agent, 5 (20%) showed TP53 mutations, 2 (40%) in exon 5, 1 (20%) in exon 5 and 2 (40%) in exon 8. Clinical response was not evaluable in 3 patients due to rapid disease progression (2 had a stop mutation in exon 5 of TP53). DCR for the remaining 25 patients was 60% in those with TP53-mutated tumors and 92% in those with TP53 wild-type disease.

      8eea62084ca7e541d918e823422bd82e Conclusion

      TP53 mutations were associated with a poorer DCR in EML4-ALK-translocated NSCLC patients treated with an anti-ALK agent. These results highlight the potential role of TP53 in determining primary resistance to anti-ALK agents, and should be confirmed in a wider case series.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      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.