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Helano Carioca Freitas
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OA 07 - Biomarker for Lung Cancer (ID 659)
- Event: WCLC 2017
- Type: Oral
- Track: Biology/Pathology
- Presentations: 1
- Moderators:Philip Christopher Mack, Shinichi Toyooka
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 503
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OA 07.08 - Clinical Potential of Sputum in Detecting Driver Mutations in Patients with Non-Small Cell Lung Cancer: A Preliminary Study (ID 7540)
17:10 - 17:20 | Author(s): Helano Carioca Freitas
- Abstract
- Presentation
Background:
The incidence of lung cancer has significantly increased over the last century and remains the most common cause of cancer deaths worldwide. Our better understanding of the tumor microenvironment and the systemic actions of tumors, combined with the recent advent of the liquid biopsy, may allow molecular diagnostics to be done with non-invasive method for detection and monitoring of patient tumors. Sputum has been the target for the discovery of non-invasive biomarkers for lung cancer because it contains airway epithelial cells, and molecular alterations identified in sputum are most likely to reflect tumor-associated changes. Since January of 2017, sputum samples have been prospectively collected at the time of diagnosis for future evaluation of actionable mutations in EGFR, KRAS, BRAF and NRAS in patients with non-small cell lung cancer in our center. Currently, from 20 sputum samples already collected, 5 are confirmed for driver mutations (one in KRAS and 4 in EGFR) in tissue biopsy, with 2 of the samples being positive for T790M in circulating tumor DNA (ctDNA) isolated from plasma. Our aim is to evaluate whether sputum may be representative in the detection of these mutations.
Method:
DNA was extracted from sputum using QIAamp DNA midi kit (Qiagen). Tumor somatic mutations were investigated by target-sequencing using a custom Ion Ampliseq™ Panel (ThermoFisher Scientific), containing hotspot regions of 14 genes frequently mutated in solid tumors (including EGFR). Multiplex amplification was performed with 10 ng of DNA using Multiplex PCR Master Mix (Qiagen) and high-throughput sequencing was performed using Ion Proton platform. Somatic mutations were considered if the variant allele was present in more than 0.5% of the reads, considering a minimum coverage depth of 20,000X. A medium coverage of 172,524X was obtained in the five samples.
Result:
We detected mutations in 3 out of 5 sputum samples of patients with previously known driver mutations (two exon 19 deletions and one exon 18 G719A in EGFR). The highest frequency was detected in the only patient with spontaneous sputum collection (23%).The other two mutations were detected in low frequencies (0.5 and 0.6%) in samples derived from sputum induction. We found T790M in one patient positive for T790M in ctDNA isolated from plasma.
Conclusion:
These preliminary findings indicate that driver mutations can be identified in sputum routinely obtained from sputum samples. Thus, the ability to examine sputum might provide a convenient source of sampling and may be adapted for future large-scale screening.
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P2.09 - Mesothelioma (ID 710)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.09-002 - Prevalence and Survival of Malignant Pleural Mesothelioma Patients Treated in a Single Brazilian Cancer Center (ID 9942)
09:30 - 09:30 | Author(s): Helano Carioca Freitas
- Abstract
Background:
Malignant pleural mesothelioma (MPM) is an unusual neoplasm, originated from the mesothelial surface of the pleural cavity. The disease is associated with occupational exposure to asbestos. Although it has low incidence, it carries an elevated morbimortality, determined by its aggressiveness and aggravated by the lack of efficient therapeutic strategies. Most patients are diagnosed at advanced stages and median overall survival (OS) remains around 9-17 months. In Brazil, some studies have suggested the number of new cases will increase till 2030, nevertheless there is no official epidemiologic data available.
Method:
Clinicopathological data from patients diagnosed with MPM and treated at A.C.Camargo Cancer Center between January/2000 and December/2014 were retrospectively collected from medical records. Demographics and clinicopathological variables were described using descriptive statistics. OS was calculated from the date of diagnosis to death. Progression-free survival (PFS) was calculated from the date of diagnosis to the date of disease progression or death. Kaplan–Meier method was used to calculate survival curves. The impact of relevant variables on survival was evaluated by the log-rank test.
Result:
We identified 29 patients between 2000 and 2014. Median follow-up was 108 months. Median age at diagnosis was 68 years (43-85y). 72.4% was men and most were Caucasian (51.7%). Tobacco consumption reported (58.6%), history of asbestos exposure (44.8%) and positive family history of cancer (34.5%). The presenting symptom was dyspnea (44.8%); followed by chest pain (24.1%). Epithelioid subtype was reported (69%) and most patients were diagnosed in stage III (34,5%) and IV (24.1%). 79% of patients were submitted to surgery: pleural decortication (36,4%), pleurodesis (31,8%), and pleuro-pneumonectomy+mediastinal lymphadenectomy (31,8%). Chemotherapy was administered to 72.4% and radiotherapy to 24.1%. Median PFS was 8 months (95%CI 5.4-10.5) and the only factor associated with improved PFS was disease resectability (resectable vs. unresectable: 10mo vs. 7mo; p=0.041). Median OS was 12 months (95%CI 5.6-18.3). Variables associated with improved OS were lack of distant metastasis at diagnosis (M0 vs. M1-MX: 15mo vs. 6mo; p=0.008) and being able to receive further lines of chemotherapy (yes vs. no: 18mo vs. 6mo; p=0.016).
Conclusion:
Since there is no national official data in Brazil, collection of local data is extremely relevant to help unraveling the epidemiological scenario in our country. Our data reinforce the low prevalence of the disease, though it could also reflect issues regarding patient referral to specialized centers. As expected, we observed an association with occupational exposure to asbestos and a poor PFS and OS.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-005 - ASTRIS: A Real World Study of Osimertinib Treatment in Patients with EGFR T790M Positive Advanced NSCLC; Interim Analysis (ID 7884)
09:30 - 09:30 | Author(s): Helano Carioca Freitas
- Abstract
Background:
Osimertinib is a third-generation, CNS active EGFR-TKI that potently and selectively inhibits both EGFR-sensitizing and EGFR T790M resistance mutations in non-small cell lung cancer (NSCLC). We report interim clinical and molecular diagnostic testing results from a predefined interim analysis of the ongoing ASTRIS study (NCT02474355).
Method:
Patients (pts) received osimertinib 80 mg once daily. Eligible pts had advanced NSCLC that had progressed on prior EGFR-TKI therapy and with a T790M mutation determined by local validated molecular test, WHO performance status (PS) 0−2, acceptable organ and bone marrow function and no history of interstitial lung disease or QTc prolongation. Asymptomatic, stable CNS metastases were permitted. The primary efficacy outcome was overall survival; other outcomes included local test methods, specimen type, EGFR mutations identified, investigator-assessed response rate (RR), progression-free survival and time to treatment discontinuation. Safety data are also reported.
Result:
From 18 Sept 2015 to the planned 3 Nov 2016 data cut-off (DCO), 1217 pts received osimertinib 80 mg once-daily across 14 countries with a median age 64 yrs (27–92 yrs), 67% female, 61% White, 37% Asian, 87% WHO PS 0/1, 44% prior chemotherapy, 45% prior radiotherapy. All pts tested positive for T790M; T790M was reported alone in 185 pts (15%). The most common testing methods were PNA-Clamp 317 pts (27%), Qiagen therascreen 254 pts (22%), and Roche cobas 204 pts (17%). Exon 19 deletion was the most common co-occurring mutation with T790M (57%), followed by L858R (27%). Tissue or cytology specimens were used in 720 pts (59%), plasma in 433 pts (36%), and other specimens in 64 pts (5%). At DCO, the median duration of exposure was 3.8 months (<1–13.2 months) with a median follow-up time of 4.1 months (<1−14 months). In pts evaluable for response, the investigator-assessed RR was 64% (569/886; 95% CI 61, 67). Adverse events (AEs) leading to dose modification and treatment discontinuation were reported in 122 pts (10%) and 54 pts (4%), respectively. Serious AEs were reported in 165 pts (14%) and AEs leading to death in 28 pts (2%).
Conclusion:
ASTRIS is the largest reported global study of osimertinib in pts with T790M-positive NSCLC identified by a wide array of molecular testing methods and from various specimen types. Considering this breadth of T790M testing, the clinical activity of osimertinib is like that observed in the clinical trial program and no new safety signals were identified.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-060 - EGFR Mutation Status by Three Sequencing Platforms in 704 Non-Small Cell Lung Cancer (NSCLC) Brazilian Patients (ID 10371)
09:30 - 09:30 | Presenting Author(s): Helano Carioca Freitas
- Abstract
Background:
EGFR status has utmost importance in treatment of NSCLC with the emergence of highly effective anti-EGFR tyrosine-kinase inhibitors (TKI). Current technologies for EGFR evaluation are based on sequencing platforms, such as Sanger, Pyrosequencing (Pyro) and Next Generation Sequencing (NGS), used in different timeframes during the last 6 years of our local practice. Indirect evidence demonstrates that Latin American patients have higher frequency of EGFR mutations. We aimed to describe EGFR mutation frequency in a Brazilian population and concordance of findings and differences between available sequencing techniques.
Method:
Between August/2010-July/2016 we performed a retrospective analysis of the reports of formalin-fixed paraffin-embedded 704 consecutive biopsy samples from TKI-naïve patients tested for EGFR at A.C.Camargo Cancer Center, São Paulo, Brazil. EGFR exons 18 to 21 were analyzed by Sanger, Pyro or NGS. All tests were performed locally.
Result:
EGFR mutation aggregated rate was 26.7% for the overall population. Table 1 shows patient’s characteristics (when medical records were available) including differences between mutated and non-mutated patients. Table 2 demonstrates differences between mutation findings for each sequencing platform.Table 1. Patient Characteristics. WT: Wild Type. Mut: Mutant.
WT EGFR Mut EGFR P value GENDER Male 223/516 (43.2%) 63/188 (33.5%) Female 293/516 (56.8%) 125/188 (66.5%) <0.001 MEDIAN AGE AT DIAGNOSIS (YEARS) 64 64.8 0.72 HISTOLOGY Adenocarcinoma 367/418 (87.8%) 156/161 (96.9%) Non-Adenocarcinoma NSCLC 51/418 (12.2%) 5/161 (3.1%) 0.01 SMOKING STATUS Nonsmoker 81/308 (26.3%) 52/128 (40.6%) Smoker/Former Smoker 227/308 (73.7%) 76/128 (59.4%) < 0.001 MEDIAN SMOKING LOAD (PACK-YEARS) 40 17.5 < 0.001 METASTASIS AT DIAGNOSIS Yes 238/333 (71.5%) 105/137 (76.6%) No 95/333 (28.5%) 32/137 (23.4%) 0.25 Table 2 – Numbers and types of mutations detected according to the test methodology.
Sanger Pyro NGS Aggregated EGFR Mutant Patients 82/352 (23.3%) 27/101 (26.7%) 79/251 (31.5%) 188/704 (26.7%) Total Number of EGFR Variants Detected* 93 28 84 205 Patients with Multiple EGFR Variants 8/82 (9.8%) 1/27 (3.7%) 5/79 (6.3%) 14/188 (7.4%) Sensitivity Variants 69/93 (74.5%) 26/28 (92.9%) 71/84 (84.5%) 166/205 (81%) Resistance Variants 3/93 (3.2%) 0 6/84 (7.1%) 9/205 (4.4%) Variants of Uncertain Significance 21/93 (22.6%) 2/28 (7.1%) 7/84 (8.3%) 30/205 (14.6%) Inconclusive test 60/352 (17%) 4/101 (4%) 5/251 (2%) 69/704 (9.8%)
Conclusion:
Our findings demonstrate higher than expected EGFR mutation rate among for caucasian patients in a Brazilian population and a numerically higher and broader EGFR mutation detection rate with NGS.
