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Ana Caroline Zimmer Gelatti



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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  |  Presenting Author(s): Ana Caroline Zimmer Gelatti

      • 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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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • 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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      P2.01-31 - Updated EGFR Mutation Frequency in 1,689 NSCLC Brazilian Patients – A National-Wide Study (ID 14267)

      16:45 - 18:00  |  Author(s): Ana Caroline Zimmer Gelatti

      • Abstract
      • Slides

      Background

      EGFR mutation status is crucial to improving therapeutic results in advanced NSCLC, due to the development of highly effective EGFR-TKIs. Recent local data suggest that EGFR mutation frequency is lower in Brazil ( 22%-33%) than in Asia and higher than in North America and Europe. We intended to describe the EGFR mutation frequency in a large national-wide Brazilian population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This retrospective analysis evaluated a database composed of samples collected between January and August 2017, from all Brazilian regions. Tumor tissue samples of patients with advanced NSCLC were submitted, at discretion of attending physicians, for EGFR mutation testing. EGFR exons 18 to 21 were analyzed by cobas®, NGS, or other non-specified test. Unfortunately, smoking status data was not available and was not included in this analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      1,689 tests were included. Table-1 demonstrates EGFR mutation rates according to test used. Mean age (±SD) was 64.5 (±11.3) for female and 66.0 (±11.1) for male population. From all detected mutations, exon 19 deletion was the most frequent (49.2%), followed by L858R (25.6%), exon 20 insertion (8.4%), T790M (4,7%), and G719X (3.0%). Patients with multiple EGFR variants (more than one EGFR mutation) corresponded to 10.3% of cases. Among different Brazilian geographic macro-regions, EGFRm rate was 33.3% in North (36 tests only), 25.1% in Northeast (307 tests), 30.9% in Central-West (175 tests), 25.8% in Southeast (841 tests), and 20.6% in the South (330 tests) region.

      Table1 – EGFR mutation rate divided by gender and EGFR mutation detection method.

      cobas®

      NGS

      Other

      Overall

      Female

      58/183

      (31.7%)

      223/586

      (38.1%)

      25/159

      (15.7%)

      306/928

      (33.0%)

      Male

      25/167

      (15.0%)

      89/447

      (19.9%)

      9/147

      (6.1%)

      123/761

      (16.2%)

      Overall

      83/350

      (23.7%)

      312/1,033

      (30.2%)

      34/306

      (11.1%)

      429/1689

      (25.4%)

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our findings confirm that EGFR mutation rate among Brazilian is higher than observed in Western countries, women have a higher EGFR mutation rate than men, and detection rate using NGS is higher than cobas®. Frequency of EGFR mutation was lower in South region, what could be explained by a higher smoking rate (not evaluated in this study) and a larger Caucasian population.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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