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Gustavo Werutsky



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    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
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      P1.01-23 - High PD-L1 Expression is Less Common Than Expected Among Advanced NSCLC in Brazil. Are We Missing the Target? (ID 13620)

      16:45 - 18:00  |  Author(s): Gustavo Werutsky

      • Abstract
      • Slides

      Background

      Immune checkpoint inhibitors improved outcomes of patients with advanced non-small cell carcinoma (NSCLC). In clinical trials 30% of patients had programmed death receptor ligand-1 (PD-L1) expression above 50% and this frequency may vary through different regions of the world. We aim to describe the real world dada on prevalence of PD-L1 expression, EGFR mutation and ALK translocation in Brazil.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Immunohistochemistry (IHC) for PD-L1, antibody 22C3 PharmDx Dako, was performed in 5 laboratories in Brazil from Aug/2017 through Apr/2018 in cases of advanced NSCLC considered for treatment with immunotherapy. Mutations in EGFR (exons 18 to 21) by Cobas®(Roche), NGS, or other non-specified tests and ALK by IHC (antibodies 5A4 or D5F3) or FISH (Vysis System) were performed in non-squamous cases. All analyses were with SAS (version 9.4). P-values <0.05 were deemed to be statistically significant.

      4c3880bb027f159e801041b1021e88e8 Result

      PD-L1 expression was assessed in 1382 samples of advanced NSCLC. The median age was 67 years, and 55.6% were male. 56.6% had adenocarcinoma, 18.0%, squamous, 20.7%, non-specified NSCLC, 2.5%, other histologies, 1.9%, missing. Of the 1380 cases, 17.4% presented PD-L1 expression ≥50%, 25.4%, 1-49%, and 57.1% <1%. The histological subtype showed association with the expression of PD-L1 (p=0,0431). In adenocarcinoma, 60.7% had no PD-L1 expression, 23.1%, had 1-49%, and 16.1%, ≥50%, while in squamous, 47.3% had no PD-L1 expression, 30.5% had 1-49%, and 22.0%, ≥50%. Among 885 samples with EGFR data, 10.9% were mutated. Both sex and histology showed association with EGFR mutation (p=0.0410 and p<0.0001). Among the men, 9.7% were mutated, while 13,4% of women were mutated. 16.4% of adenocarcinoma and 3.1% of squamous had EGFR mutation. In 855 samples with ALK data, 3.5% were rearranged. ALK rearrangement was associated with sex and age (p=0.0388 and p=0.0088) and was 2.2% in men and 4.8% in women. The group with age <50 had a higher prevalence of ALK rearrangement (8.6%). Among 735 patients without EGFR mutations or ALK rearrangements, 16.8% had PD-L1 ≥50% and 24.0% had 1-49%.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results indicate a lower overall prevalence of PD-L1 expression in advanced NSCLC in Brazil as compared with clinical trial data. Among other potential factors, inadequate sample handling, pre-analytical issues, or epidemiology of the biomarker may impact PD-L1 expression. Prevalence of EGFR mutations and ALK translocations was within the range of prior publications in the country. Further regional and institutional analysis will be presented to better characterize the variations in prevalence of these biomarkers outside clinical trials.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    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
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      P2.13-09 - Efficacy and Safety of Osimertinib After Prior EGFR TKI: Analysis of Patients Underrepresented in Randomized Clinical Trials (ID 14036)

      16:45 - 18:00  |  Author(s): Gustavo Werutsky

      • Abstract
      • Slides

      Background

      Osimertinib is a new standard of care in non-small cell lung cancer (NSCLC) after progression to an EGFR TKI in the presence of T790M mutation. Following results of the phase III study AURA 3, which led to the approval of osimertinib worldwide, we have conducted ASTRIS in Brazil.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a phase IV, international, multicentric, open trial, with the aim of confirming the efficacy and safety of osimertinib at a dose of 80 mg daily, orally. Eligible patients presented with diagnosis of T790M-positive NSCLC on progression after prior EGFR TKI. Herein, we present the Brazilian experience at ASTRIS, including subsets that were underrepresented in the phase III trial.

      4c3880bb027f159e801041b1021e88e8 Result

      Eighty-eight patients were enrolled in Brazil between August 2015 and March 2017. The median age was 64 years (34-89), and most were females (66%). Fifty-four patients (61%) had received prior therapy with erlotinib, forty-two (48%) with gefitinib, and 3 (3%) with afatinib. Nineteen patients (22%) were exposed to a EGFR TKI more than 6 months before enrolment. Importantly, 11 patients (12.5%) presented with a PS of 2, 23 (26%) presented with brain metastases, and 3 with leptomeningeal disease. Exon 19 deletions were the most common primary mutation in EGFR, present in 55 cases (62.5%), followed by L858R in 24 cases (27%). Tumor samples were acquired from the primary tumor in 14 cases (45%) and in a metastatic site in 16 (52%); all other cases had T790M detected at plasma. After a median follow-up of 9.3 months, 26 progression events and 23 deaths were documented. The response rate was 58.2% (95%CI 46.6-69.2), and median progression-free survival was 9.4 months (95%CI 8.2-not reached). The 12-month overall survival was 69.7% (95%CI 56.5-79.6). Thirty patients (34%) presented an adverse event, 14 of which led to dose modification and 5 to treatment discontinuation. The most common adverse events were infection in 14 cases (15%), gastrointestinal and hematologic (4 cases each). Nineteen patients (22%) had a serious adverse event, mostly infections (14 cases).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The profile of patients enrolled in Brazilian institutions highlights the presence of cases with poor PS, which was excluded in the AURA 3 trial. Despite these features, the efficacy and safety of osimertinib was confirmed, suggesting that results could be extrapolated to a broad range of subsets. This study also underscores the role of liquid biopsy in the detection of T790M, in detriment to tumor re-biopsy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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