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G. Recondo
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-058 - Real World Data with Nivolumab: Experience in Argentina (ID 8800)
09:30 - 09:30 | Author(s): G. Recondo
- Abstract
Background:
Nivolumab has improved overall survival (OS) in metastatic non-small cell lung cancer (NSCLC) patients. Analysis of the use of these drugs in real world provides more evidence about efficacy and toxicity. We describe here the experience of the use of nivolumab in NSCLC in Argentina.
Method:
NSCLC patients (pts) who received nivolumab between 6/2015 - 12/2016. Patients consented their respective physicians to be treated on a drug expanded access program. Data was collected retrospectively by the physician. Images and follow up were done according to physician´s discretion. Adverse events were classified according to CTC3.1. Responses were evaluated according to RECIST 1.1 criteria. DFS and OS was assessed. All pts who received at least one dose of Nivolumab were evaluated for toxicity.
Result:
N 109. Fup 8.83 m (IQR 3.4-12.67). 57.8% men, 29.4% current smoker, 78.0% non-squamous, 8.3% EGFR mutated. Chemotherapy lines before nivolumab 2 md (r 1-4), and 59.6% received radiotherapy. 89% received previously platinum based chemotherapy. Sites of relapse or progression before nivolumab were: lung (75.2%), lymph nodes (47.7%), bone (19.3%), liver (11.9%), central nervous system (11.0%), and adrenal gland (13.8%). PS 0 26.6%, 1 56.0%, 2 13.8% and 3 1.8%. Cycles of nivolumab 10 Md (IQR 3-18). Drug related toxicity 78.9%. Grade 2-3 28.4%. Corticoid use 33.9%. Responses were evaluated in 104 pts who had as best response CR 2/104 (2%), PR 28/104 (27. %), SD 33/104 (32%) and PD 41/104 (39.%). Time to the best response was 4.0 m (IQR 2.3-5.9). DFS 6.1 m (IQR 2.4-13.1) and OS 12.3 m (IQR 4.1-NR). Univariate analysis revealed that absence of corticoids use (p=0.034), toxicity grade 1-3 (p=0.0025), PS≤1 (p=0.049), age<=50 (p= 0.0011) were associated with longer DFS; PS≤1 (p<0.001) and toxicity grade 1-3 (p=0.001) were associated with longer OS. In multivariate cox regression analysis, toxicity grade 1-3 (HR 0.44 CI95% 0.24-0.81, p=0.008) and age<=50 (HR 0.28 CI95% 0.13-0.61, p=0.001) were associated with longer DFS while corticoids use was associated with shorter DFS (HR 2.06 CI95% 1.22-3.48, p=0.007); toxicity grade 1-3 (HR 0.28 CI95% 0.14-0.54, p<0.0001) and PS≤1 (HR 0.16 CI95% 0.08-0.31, p<0.0001) were associated with longer OS.
Conclusion:
The use of Nivolumab in a real world setting, in heavily pre-treated NSCLC patients was well tolerated and showed promising clinical efficacy. PS, the use of corticoids and immune-mediated toxicity seem to be conditions which could affect clinical outcomes.
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-035 - Human Papillomavirus Infection in Lung Squamous Cell Carcinoma and Correlation to p16 INK4a Expression from an Argentine Population (ID 9561)
09:30 - 09:30 | Author(s): G. Recondo
- Abstract
Background:
Lung cancer is the leading cause of cancer death worldwide. In 1979, Syrjänen suggested a role for human papillomavirus (HPV) infection in bronchial carcinoma. Many studies have found HPV on lung carcinoma, predominantly in squamous cell carcinoma (SCC). There seems to be a geographical factor determining prevalence rates. In Latin America, only 2 studies, altogether including 51 cases of lung SCC, examined this association. However, data from Argentina is lacking. The aim of this study is to asses the incidence of HPV infection in lung SCC of Argentinean population, and to correlate with p16[INK4a ]expression from an Argentine population.
Method:
The study was approved by CEMIC’s Ethics Committee. Informed consent was obtained. Materials consisted of formalin-fixed paraffin-embedded (FFPE) tissue from 29 surgically excised and 11 transbronchial biopsies of primary L-SCC evaluated between 2006-2016. HPV Genotyping: On 50μm-thick slides, tumor was microdissected and DNA was extracted (columns method). Wide-spectrum HPV DNA (L1-ORF) was amplified by PCR. Positive specimens were genotyped by PCR for types 16 and 18. Immunohistochemistry: All p16 staining’s were performed on VENTANA BenchMark GX using antibody CINtec® p16. Staining patterns were interpreted on a binary way (positive or negative). Only cases with diffusely intense cytoplasmic and/or nucleic staining on tumor cell (TC) were considered positive. Cases in which the normal bronchial epithelium resulted p16 positive but TC were negative, were also registered.
Result:
HPV was isolated in 10/40 cases (25%). The details of HPV infection and the clinicopathological data is depicted on table 1.Clinicopathological features of SCC
HPV positive (n=10) HPV negative (n=30) Gender Female 5 11 Male 5 19 Age <50 1 - 50-60 - 21 >60 9 9 Smoking Never-smoker - - Smoker - - Unknown 10 30 Tumor cell differentiation Well 1 - Moderate - 10 Poorly 9 20 Keratinizing Non-keratinizing 9 27 Keratinizing 1 3 p16 positive on tumor cellls Positive 3 2 Negative 7 28 p16 on bronchial epithelium Positive 3 2 Negative 7 28 HPV type HPV 16 3 - HPV 18 5 - Co-infection HPV 16 and 18 2 - Specimen type Transbronchial biopsy 3 8 Surgical excision 7 22
Conclusion:
We detected an HPV infection rate of 25%. HPV18 was the common genotype. On 7 cases, normal bronchial epithelium was both p16 and HPV positive, suggesting that adjacent tumor tissue may be HPV infected. p16 should not be used as a surrogate marker for HPV infection, since it is only positive on 60% of cases.
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-007 - Molecular Characterization of Non-Small Cell Lung Cancers (NSCLC) in Young Patients from an Argentine Population (ID 7951)
09:00 - 09:00 | Author(s): G. Recondo
- Abstract
Background:
NSCLC is the leading cause of cancer-related deaths in Argentina. NSCLC is rarely observed in young adults (aged 18-40 years) and presents distinctive molecular characteristics. This study analyzed the prevalence of oncogenic molecular alterations in tumor samples from young adults treated at our institution. Different molecular biology techniques were used and treatment outcomes were reported.
Method:
Retrospective observational study of FFPE tumor samples from individuals aged 18-40 years, presenting stage IV lung adenocarcinoma. ALK fusions were studied by IHC (clone-D5F3) and confirmed with FISH-Vysis. The areas selected for molecular studies were micro-dissected, and DNA/RNA were purified. EGFR mutations were studied by Sanger. If available, targeted NGS was done with Colon and Lung. Cancer Research Panel v2 (CLRP) for DNA analysis; and/or Oncomine™ Panel Focus Assay (OFA) for DNA/RNA analysis. Both panels were performed in an Ion 520 chip sequenced in the Ion S5 Next Generation Sequencing Systems. The sequences obtained were analyzed in the Ion Reporter™ Software 5.2.1. The OFA was informed by Ion Torrent™ Oncomine™ Knowledgebase Reporter.
Result:
Six patients were included, 5/6 tumors were lung adenocarcinoma and 1/6, poorly differentiated carcinoma. The male:female ratio was 2:1. Median age was 35y (range 32-37) and all subjects had stage IV disease. EGFR and ALK were tested in all patient's samples, and 4/6 had NGS analysis. Five samples (83%) harbored known targetable oncogenic drivers: EGFR sensitizing mutations occurred in 3/5, ALK translocation with KRAS co-mutation in 1/5, and HER2 exon 20 insertions in 1/5. Only one sample without NGS was negative for the studied oncogenes. Targeted therapies were administered to 4/5 patients. Figure 1
Conclusion:
Our series shows a high prevalence of known actionable oncogenic drivers in young patients with NSCLC tumor. In this population an extensive molecular profiling of tumors is required to improve the treatment strategy.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-071 - Prospective Molecular Study of 22 Genes by NGS in Patients with Non-Small Cell Lung Cancer (NSCLC) in Argentina: A Single Institution Experience (ID 7950)
09:30 - 09:30 | Author(s): G. Recondo
- Abstract
Background:
Next generation sequencing has contributed to understanding the biology of NSCLC and to improve therapy selection. The prevalence of other oncogenic alterations beyond EGFR, ALK and KRAS in Argentina remains unknown. The aim of this study was to characterize the genomic lanscape of NSCLC tumors from 45 patients in our institution by NGS.
Method:
Prospective observational study. We included 45 patients, over 18 years old, with diagnosis of NSCLC and adequate tumor sample. DNA was purified from FFPET samples. Targeted NGS was done with Colon and Lung Cancer Research Panel v2 (Ion Torrent™ AmpliSeq™ technology) for 22 genes with Ion 520 chip, sequenced in Ion S5 Next Generation Sequencing Systems.
Result:
Forte five patients were included in the analysis, 19 female (42%) and 26 male (58%). Median age was 57 years old (range 34-89). Most patients had lung adenocarcinoma 43 (96%), 1 squamous (2%) and 1 adenosquamous histology (2%). A total of 28 patients (62%) had stage IV lung cancer, 18% stage III, 4% stage II and 16% stage I. From 43 evaluable samples, 65 mutations were detected: TP53 n=21, KRAS n=20, EGFR n=9, BRAF n=5, MET n=3, ERBB2 n=2, FGFR3 n=2, PI3K n=2, FGFR2 n=1. Of these, 10 are associated with clinical benefit with approved targeted therapies. Two samples had novel EGFR mutations and 2 had EGFR co-activating mutations (Del19 + L858R; and G719C + S768I). KRAS and TP53 co-mutations were present in 50% of KRAS mutant samples. We encountered 26 variants of unknown significance. In our population, 37 samples (86%) had EGFR Q787Q (c.2361G>A) polymorphism.Figure 1
Conclusion:
The distribution of oncogene mutations in patients with NSCLC in our institution in Argentina is similar to other western countries with the exception of higher KRAS mutant patients in this cohort. An ongoing larger trial will provide further information for our country and the region.
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-039 - Compassionate Use of Osimertinib: Argentine Experience (ID 9447)
09:30 - 09:30 | Author(s): G. Recondo
- Abstract
Background:
EGFR is one of the most commonly mutated proto-oncogenes in lung cancer. The frequency of these mutations varies from approximately 10% of lung adenocarcinomas in North American and European populations to 50% in Asia. The leucine to arginine substitution at position 858 (L858R) in exon 21 and short in-frame deletions in exon 19 are the most common sensitizing mutations, comprising approximately 90% of cases. Approximately 50% of EGFR TKI resistance is due to a second site mutation, the T790M mutation occurring within exon 20.
Method:
To describe the "real life" experience in our country regarding the compassionate use of Osimertinib in patients with diagnosis of lung cancer with EGFR mutation and progression to tyrosine kinase inhibitors with detectable T790M mutation. We also include patients with de novo T790M mutation. We evaluated demographic data, the diagnostic method of resistance, sites of disease progression, toxicities and treatment efficacy.
Result:
We analyzed 17 patients from 10 different centers in Argentina in the period between January 2016 and May 2017. Median age: 61 years old, female 76%, PS: 0-1: 86%, non-smokers: 59%, histology: 15 adenocarcinoma and 2 undifferentiated, 14/17 with stage IV at diagnosis. EGFR mutations: Exon 19: 9 patients, 3 patients with evidence of T790M de novo, the remainder between exons 21 and 18. At the time of diagnosis, 13 patients start treatment with tyrosine kinase inhibitors, and the median time of response was 17 months. The most frequent site of progression was lung/pleura (85%) and liver (21%). Re-biopsy was performed in 13/17 patients. The major difficulty for successful biopsy was the site or the complexity of the procedure to be performed. A liquid biopsy was performed in 6 of 17 patients, 4 were positive. ORR with Osimertinib was 68%. The most common side effects were diarrhea: 31% (only 1 patient with grade 3), rash 18%. One patient had liver toxicity (grade 3 hepatitis).
Conclusion:
Osimertinib showed better adhesion and tolerance profile than tyrosine kinase inhibitors. Osimertinib offers an excellent toxicity profile with overall response rates similar to those described in publications.
