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P. Archila



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    MA 01 - SCLC: Research Perspectives (ID 650)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      MA 01.02 - Multigene Mutation Profiling and Clinical Characteristics of Small-Cell Lung Cancer in Never-Smokers Versus Heavy Smokers (ID 10335)

      11:00 - 12:30  |  Author(s): P. Archila

      • Abstract
      • Presentation
      • Slides

      Background:
      Small-cell lung cancer (SCLC) has been occasionally detected in never-smokers as smoking rates decrease worldwide. We investigated the clinical and genetic characteristics of SCLC in never-smokers (Geno1.3-CLICaP)

      Method:
      A cohort of patients diagnosed with SCLC were grouped into smokers (n=10) and ever/never-smokers (n=10). For both groups, somatic mutation profiling was carried out using a comprehensive NGS assay (TruSight Tumor 170) targeting the full coding regions of 170 cancer-related genes. Epidermal growth factor receptor (EGFR) mutation was confirmed by RT-PCR (Cobas[TM]). The clinical outcomes of the two groups were compared using Kaplan-Meier and Cox proportional models.

      Result:
      Median age was 58 years (r, 46-81), 55% (n = 11) were men, most patients had extended disease (85%) and the dominant tumor involvement site was pleura and lungs (65%). No significant differences were found in age, disease distribution, baseline performance status and cerebral metastases in relation to tobacco exposure. The ORR to first-line therapy were 50% and 90% between smokers and ever/never-smokers, respectively (p=0.032). The median overall survival (OS) was 29.1 months in ever/never-smokers (95%CI 23.5-34.6) versus 17.3 months in smokers (95%CI 4.8-29.7; p=0.0054). Never-smoking history (HR 0.543, 95%CI 0.41-0.80), limited stage disease (HR 0.56, 95%CI 0.40-0.91) and response to first line platinum based chemotherapy (HR 0.63, 95%CI 0.60-0.92) were independently related with good prognosis. Among ever/never smokers main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), EGFR (30%), MET (20%), SMAD4 (20%) and BRIP1 (20%). None of the smokers had mutations in EGFR, MET or SMAD4, but there was a greater involvement in RB1 (80%, p=0.04), CDKN2A (30%, p=0.05), CEBPA (30%, p=0.05), FANCG (20%), GATA2 (20%), and PTEN (20%).

      Conclusion:
      Never-smokers with SCLC are increasingly prevalent and have a better prognosis than their smoker counterpart. EGFR, MET and SMAD4 are frequent mutations among SCLCs of ever/never smokers, and RB1, CDKN2A and CEBPA among smokers. Figure 1



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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-055 - Genotyping Squamous Cell Lung Carcinoma Among Hispanics (Geno1.1-CLICaP) (ID 10166)

      09:30 - 16:00  |  Author(s): P. Archila

      • Abstract
      • Slides

      Background:
      Lung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer subgroup, largely because of a lack understanding of the molecular pathogenesis of the disease. To characterize SCC genomic profile among Hispanics we tested diverse alterations using a validated next generation sequencing (NGS) platform.

      Method:
      We performed sequencing using a comprehensive NGS assay (TruSight Tumor 170) targeting the full coding regions of 170 cancer-related genes on 26 squamous cell lung cancer samples from Hispanic patients. PD-L1 expression in tumor cells (TCs) was assessed using clone 22C3 (Dako) and main clinical outcomes like progression free survival (PFS), overall response rate (ORR), and overall survival (OS) were recorded.

      Result:
      Median age was 67 years (range, 33-83), 53.8% were men and all patients had previous exposure to tobacco (former 69.2%/current 30.8%) with a mean consumption rate of 34-year package. Almost all patients (80.8%) received cisplatin or carboplatin plus gemcitabine as first line with an ORR of 61.5%, a median PFS of 12.0 months (95% CI 10.9-13.2) and OS of 24.8 months (95% CI 20.8-28.7). We found a relatively high prevalence of inactivating mutations in TP53 (61.5%), PIK3CA (34.6%), MLL2 (34.6%), KEAP1 (30.8%) and NOTCH1 (26.9%). In addition, genetic alterations in the NF1 (19.2%), RB1 (15.4%), STK11 (15.4%), SOX2 (11.5%), PTEN (7.7%), KRAS (3.8%) and HRAS (3.8%). Distribution of PD-L1 expression were: negative, 1%, 2-49% and ≥50% in 23.1%, 38.5%, 26.9% and 11.5%, respectively. None of the genetic alterations affected PFS, OS or ORR and PDL1 expression was lower among those who had mutations in TP53 (p=0.037) and PIK3CA (p=0.05).

      Conclusion:
      We identified previously described mutations among Hispanic patients with SCC. Lower PDL1 expression was also found among those who had alterations in TP53 and PIK3CA.Figure 1



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    P3.02 - Biology/Pathology (ID 620)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P3.02-063 - EGFR Exon 20 Insertions in Lung Adenocarcinomas: Molecular and Clinicopathologic Characteristics Among Hispanics (Geno1.2-CLICaP) (ID 10406)

      09:30 - 16:00  |  Author(s): P. Archila

      • Abstract
      • Slides

      Background:
      In contrast to other primary EGFR mutations in lung adenocarcinomas, insertions in exon 20 of EGFR have been generally associated with resistance to EGFR tyrosine kinase inhibitors. Their molecular spectrum, clinicopathologic characteristics and prevalence are not well established among Hispanics.

      Method:
      Tumors harboring EGFR exon 20 insertions were identified through a comprehensive screening of 4.500 lung adenocarcinomas from diverse Latin American Countries. Cases were tested for common and uncommon EGFR mutations and KRAS. Almost all cases (n=52) underwent extended genotyping for other driver mutations in BRAF, NRAS, PIK3CA, Her2 and MEK1 by NGS (TruSight tumor[TM]), EGFR amplification, ALK and PDL1 protein expression (D5F3CDx Assay and 22C3 Clone). Clinical outcomes were evaluated using Kaplan-Meier and Cox proportional models.

      Result:
      60 patients were included; median age was 66-yo (r, 24-79), 63.3% were females, most patients had a micropapillary (38.3%) or lepidic (20.0%) adenocarcinomas, 61.7% were never smokers and 36.7% had brain metastasis at diagnosis. 14 patients (23.4%) had common EGFR mutations (del19/L858R) in addition to the exon 20 insertion, 5 (10.0%) had non-common EGFR mutations (G719X /L861Q/S768I) plus the exon 20 insertion, and two cases had additional mutations in PIK3CA and MEK1. Insertion sequences were highly variable, with the most common variant (V769_D770insASV) making up only 21.7% of cases. 30% of patients had amplification of the EGFR and 75% had a PDL1 expression level of less than 50%. Overall response rate (ORR) to the first line was 30%, progression free survival (PFS) was 8.3 months (95%CI 6.9-9.6) and OS was 17.4 months (95%CI 16.4-19.5). Prognosis was positively influenced by concomitant presence of common EGFR mutations (p=0.016) and by response to first line therapy (p=0.06).

      Conclusion:
      Patients with EGFR exon 20 insertions have similar clinical characteristics to those with common EGFR mutations but a poorer prognosis. The mean PDL1 expression in this population appears to be higher than in patients with common EGFR mutations, finding that promote the potential use of immunotherapy alone or in combination for this population.

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