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Helano C. Freitas
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EP1.04 - Immuno-oncology (ID 194)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.04-44 - Exploration of Factors Relating to Paradoxical Immune Response in Patients Treated with Immune Checkpoint Inhibitors for NSCLC (Now Available) (ID 2634)
08:00 - 18:00 | Author(s): Helano C. Freitas
- Abstract
Background
Although the introduction of immune checkpoint inhibitors (ICIs) has yielded substantial benefits in terms of survival in the treatment of Non-Small Cell Lung Cancer (NSCLC), the possibility of activation of dormant autoimmune diseases or onset of immune mediated toxicities is a reality. The objective of this study was to explore intrinsic immunological factors associated with poor outcomes.
Method
In a retrospective cohort study of 48 patients, without any prior medical history of autoimmunity, treated for advanced/metastatic NSCLC with ICI´s were assessed. Determination of HLA-A*02011 as well as acute phase reactants and antiphospholipid antibodies was performed. Additionally, evaluation of survival in a time to event manner was conducted using the Kaplan Meier method and Cox regressions
Result
Median follow-up was 27.3 months, of the included patients 26 were male (54%) with a median age of 62 years old and there were no individuals with and ECOG performance score >1. Median overall survival (OS) was reached at 22.47 months. When analyzing the presence of the HLA-A*02011 serotype, 6 patients tested positive (12.5%). Additionally, all presented with borderline or abnormal B2glycoprotein IgM and IgG, 2Bmicroglubulin and elevated C reactive protein. Four patients (66%) experienced reactive lymphadenopathy during treatment and all suffered some form of venous thromboembolism. When analyzing OS, this group of patients had a significantly worse outcome (6.53 vs 22.47 months, HR= 4.47, [95%CI 1.47 – 13.61], p<0.001) compared with their counterparts. Overall response rate for the whole was superior for the HLA-A*02011 positive patients achieving 41.4% and 33%, p<0.001, respectively.
Conclusion
The presence of the HLA-A*02011 could potentially predispose to a paradoxical and pathological activation of the immune system without offering any benefit in terms of tumor control. Larger studies validating these findings are warranted.
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EP1.04-45 - Relevance of Antibiotic Use on Clinical Activity of Immune Checkpoint Inhibitors in Hispanic Patients with Advanced NSCLC (CLICAP-ABs) (Now Available) (ID 2674)
08:00 - 18:00 | Author(s): Helano C. Freitas
- Abstract
Background
The composition of gut microbiota affects antitumor immune responses, as well as preclinical and clinical outcomes following immune checkpoint inhibitors (ICI) in cancer. Antibiotics (ATB) alter gut microbiota diversity and composition leading to dysbiosis, which may influence the effectiveness of ICI.
Method
We examined patients with advanced non-small-cell lung cancer (NSCLC) treated with anti-programmed cell death ligand-1 mAb monotherapy alone or in combination in three different countries of Latin America. Those receiving ATB within 30 days of beginning ICI were compared with those who did not. Objective response, progression free survival (PFS) and overall survival (OS) were assessed.
Result
18 of 140 (13%) NSCLC patients received ATB. The most commonly used ATB were b-lactam or quinolones for pneumonia or urinary tract infections. In NSCLC patients, ATB was associated with 4 cases of primary PD (28.6% versus 31.5%, P=0.818), non-significant decreased PFS (median 2.66 versus 1.94 months, HR 1.63, [95% CI 0.71-3.72], P=0.247) and significantly deleterious OS (median 12.42 versus 2.04 months, HR 2.3, [95% CI 1.08-4.95], P=0.03). In multivariate analyses, the impact of ATB remained significant for OS.
Conclusion
ATB were associated with reduced clinical benefit from ICI in Hispanic patients with NSCLC. Modulation of ATB-related dysbiosis and gut microbiota composition may be a strategy to improve clinical outcomes with ICI.
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EP1.15 - Thymoma/Other Thoracic Malignancies (ID 205)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Thymoma/Other Thoracic Malignancies
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.15-28 - Survival of Thymoma Is Extensive in Latin-American Patients: Results from Over 10 Years of Experience (CLICaP-LATimus) (ID 2936)
08:00 - 18:00 | Author(s): Helano C. Freitas
- Abstract
Background
Thymomas are a group of rare neoplasm of the anterior mediastinum. Due to their low incidence, large cooperative studies are required to evaluate outcomes. The objective of this study is to present the results and experience in treatment of this pathology in Latin-America.
Method
A retrospective multicenter cohort study was conducted by The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP). Patients with histologically proven thymomas between 1997 and 2018 were included in the analysis. Variables including clinical, pathological and therapeutic outcomes were registered in a centralized manner.
Result
A total of 105 patients were included. Median age at diagnosis was 54 years old (20-84), and with 60% (n = 38) of the included patients were female. Only 11% (n=7) of the patients had an ECOG performance score >1. Twenty-four patients (22.9%, 95%CI 14.8-30.9) presented with pulmonary or distant metastatic involvement with a median of 2 metastatic sites. Furthermore, 21.9 % of patients (n=23, 95%CI 13.9-29.8%) concurrently presented myasthenia gravis. Surgery was performed in 55 patients (52.3%, 95%CI 42.8 – 61.9%), comprising of 15 tumorectomies, 37 thymectomies and 5 biopsies achieving an R0 resection rate of 78% (95%CI 67.3-89.1%). Adjuvant treatment in the form of either chemotherapy, radiotherapy or both was offered to 3(5%), 7(12.7%) and 5(9%) patients, respectively. Disease progression was documented in 10 cases (9%, 95%CI3.9-15.1%) of which 6 (60%) were locoregional, 1 (10%) distant progression and 3 (30%) both locoregional and distant. Median overall survival (OS) was estimated at around 139.5 months (95%CI 86.1-NA). Cox regression indicated that OS was significantly improved by resection (139.5 vs 25.7 months, HR 4.17 [95%CI 12.6-17.8 months]).
Conclusion
Survival in patients with thymomas continues to be very favorable, especially in patients who receive adequate local control. The benefit of adjuvant treatment in this setting remains unclear.
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EP1.15-29 - Real World Characterization and Treatment of Patients with Thymic Carcinoma: Lessons from a Latin-American Study (CLICaP-LATimus) (Now Available) (ID 2921)
08:00 - 18:00 | Author(s): Helano C. Freitas
- Abstract
Background
Thymic carcinoma is a rare tumor that represents a clinical challenge, especially in resource limited settings. The objective of the present study was to characterize patients who presented this disease in Latin-America.
Method
From 2014 until 2018, a multinational Latin-American cooperative retrospective cohort study was performed. Patients with histologically confirmed thymic carcinoma were included. Clinical, pathological and treatment variables were collected across 7 participating nations.
Result
A total of 31 patients were included. Median age at diagnosis was 58 years old (34-69), 48% (n=15) of individuals were women with all but 2 patients (6.5%) achieving an ECOG performance score <2. All patients debuted with Stage IV disease; 24 patients (66%, [95%CI 62-92%]) as stage IVa and 7 as stage IVb (33%, [95%CI 7-37%]) with a median LDH level of 396.5 U/L (153-1529 U/L) and a median of 2 metastatic sites. 13 (41.9%, [95%CI 25-59%]) patients received preoperatory treatment consisting of chemotherapy (n=8, 42%) and chemoradiotherapy (n=5, 16%). Among these patients only 4 (12.9%) were subjected to surgery, two of which underwent a tumorectomy and 2 a thymectomy. 28 (90%, [95%CI 79.9-100%]) received palliative chemotherapy either with sunitinib (n=7, 25%) or cytotoxic agents. Median overall survival (OS) was reached at 20.2 months (95%CI 19-NA months). Patients who received preoperative treatment had a significantly prolonged OS (17.6 vs 26 months, HR 2.93 [95%CI 1.04-8.27 months], p = 0.03).
Conclusion
Thymic carcinoma constitutes an aggressive disease that is often diagnosed in advanced stages. These results suggest that multimodal treatment can be beneficial even in locally advanced cases. Larger clinical trial validating these conclusions are warranted.
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-76 - Predictive Factors of Early Therapeutic Failure to Immunotherapy in Patients with Metastatic NSCLC (ID 974)
09:45 - 18:00 | Author(s): Helano C. Freitas
- Abstract
Background
Immunotherapy helped to improve the outcomes of patients diagnosed with metastatic NSCLC. Nevertheless, survival curves show that some patients do not benefit from treatment and progress rapidly. Identifying factors capable of predicting early failure to immunotherapy is clinically useful. We determined factors associated with disease progression before nine weeks of treatment with anti-PD1.
Method
We retrospectively reviewed the medical records of patients with metastatic NSCLC treated in second or more line with anti-PD1 at AC Camargo Cancer Center-Brazil, from January 2006 until April 2018. Altogether, 87 patients were identified and had pre-treatment (data collected within 30 days of immunotherapy initiation) characteristics collected. Univariate analysis was performed using binomial logistic regression (disease progression occurring till 9 weeks versus after); variables with p value < 0.20 were selected for multivariate analysis. A multivariate model to predict disease progression (DP) until 9 weeks was developed using the likelihood ratio test and Akaike Information Criteria (AIC). Median follow-up was estimated using reverse Kaplan-Meier method. Median progression-free (mPFS) and overall survival (mOS) were obtained from Kaplan-Meier curves.
Result
Median follow-up was 18 months (95% CI 14.0-20.3), mPFS was 3.3 months (95%CI 2.1-3.7) and mOS was 15.8 months (95%CI 7.5-25.5). Univariate analysis demonstrated that the number of metastatic sites (OR=1.79; 95%CI 1.25-2.68; p=0.002), hemoglobin level (OR=0.791; 95%CI 0.55-0.88; p=0.003), monocyte count (OR=1.24; 95%CI 1.08-1.47; p=0.004), platelet count (OR=1.44; 95%CI 1.01-2.14; p=0.051), dNLR (derived neutrophil to lymphocyte ratio) (OR=1.19; 95%CI 0.95-1.54; p=0.14), ECOG (OR=2.43; 95%CI 1.00-6.048; p=0.051), T stage (OR=2.15; 95%CI 0.78-6.14; p=0.14), N stage (OR=4.26; 95%CI 1.51-14.13; p=0.010) and treatment line (OR=0.53; 95%CI 0.22-1.25; p=0.15) were significantly associated with early treatment failure. The final multivariate model demonstrated that N stage (OR=8.14; 95%CI 1.50-44.11; p=0.015), the number of metastatic sites (OR=2.10; 95%CI 1.24-3.55; p=0.005), hemoglobin level (OR=0.62; 95%CI 0.44-0.89; p=0.010), monocyte count (OR=1.44; 95%CI 1.12-1.84; p=0.004) and dNLR (OR=1.40; 95%CI 1.03-1.91; p=0.029) are independent factors associated with DP until 9 weeks of treatment.
Conclusion
N stage, the number of metastatic sites, hemoglobin level (g/dL), the monocyte count and the dNLR are factors independently associated with early disease progression (until 9 weeks from immunotherapy initiation). This can help to better select metastatic NSCLC patients for anti-PD1 therapy in second line.
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P1.04-80 - Immunotherapy-Related Thrombosis: Considerations and Associated Factors in Non-Small Cell Lung Cancer (NSCLC) Patients (ID 2724)
09:45 - 18:00 | Author(s): Helano C. Freitas
- Abstract
Background
Widespread use of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer has exposed a large number of patients to these medications, increasing the incidence of rare adverse reactions such as thromboses. The present study elaborates on factors related to the occurrence of these events.
Method
In a retrospective cohort study, a total of 48 patients, 24 who experienced thrombosis and 24 matched controls who underwent evaluation after initiation of ICIs therapy for advanced/metastatic NSCLC, were included. Clinical and pathological as well as serum inflammatory and coagulation markers were evaluated.
Result
Among the 48 patients, 46% (n=26) were female, median age was 62 years old and all patients had an ECOG performance score of < 2. The median overall survival reached by the cohort was 22.47 months. Among patients who developed thrombosis there were 8 cases of deep venous thrombosis (DVT) (33%), 13 pulmonary embolisms in addition to DVT (62.5%) and 1 case of brain venous sinus thrombosis (4.2%). Apart from expected thrombosis markers such as D dimer, differences in inflammatory and immune related markers between patients who experienced thrombosis and those who did not, were observed. Abnormal values were found in the thrombosis group for B2glycoprotein 1 (33% vs 0%, OR= 4.08, [95%CI 1.65 - 12.1], p= 0.005), B2glycoprotein 1 IgG (29.2% vs 0%, OR= 4.64, [95%CI 1.73 – 16.9], p= 0.007), C Reactive protein (83.3% vs 12.5%, OR= 35, [95%CI 7.9 - 213], p< 0.001), B2microglobulin (62.5% vs 8.3%, OR= 14, [95%CI 3.11-103.7], p = 0.002), Prothrombin time (41.7% vs 4.2%, OR= 2.4, [95%CI 1.64 -3.69], p =0.01) and C Coagulation protein (50% vs 16.6%, OR =1.79, [95%CI 1.53 – 2.91], p <0.001).
Conclusion
Abnormalities in antiphospholipid antibodies, C reactive protein, B2microglobulin and coagulation in patients who suffered thrombosis during ICI treatment suggest that this phenomenon could be the result of immune and auto-inflammatory induced intravascular dysfunction.
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P1.11 - Screening and Early Detection (ID 177)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.11-38 - Frequency and Prognostic Impact of Concomitant Mutations in KRAS and TP53 or STK11 in Brazilian Lung Adenocarcinoma Patients (ID 2576)
09:45 - 18:00 | Author(s): Helano C. Freitas
- Abstract
Background
Previous studies reported that co-occurring genomic alterations in KRAS and STK11/LKB1 or TP53 tumor suppressor genes define subgroups of KRAS-mutant lung adenocarcinomas (LADC) with distinct biology, therapeutic vulnerabilities, and immune profiles. The impact of concomitant STK11, TP53 and KRAS mutations in Brazilian lung cancer patients remains poorly explored.
Aims: In our preliminary study, we investigated the frequency of STK11 and TP53 in KRAS mutant or wild-type LADC. STK11 and TP53 mutational status was correlated with clinico-pathological characteristics and overall survival (OS).
Method
This is a retrospective analysis which included 27 consecutive LADC patients treated with platinum-based chemotherapy and/or immunotherapy. Mutational status analysis was performed using the Illumina TruSight Tumor 26™ panel based on multiplex-PCR. This customized multiple genes panel covers 26 critical oncogenes or tumor supressor genes including: exons 2–4 of KRAS, exons 1–9 of STK11 and 1–11 of TP53, specifically considered in the current study. Kaplan-Meier method was used to calculate overall survival and the univariate Cox model was used to compare survival.
Result
Among the 27 patients included, 23 (85%) were KRAS mutant (KRASmut), 15 (55.6%) were TP53 mutant (TP53mut) and 5 (18%) harbored a STK11 mutation (STK11mut). From all mutant cases, 10 (37%) were KRASmut only; 4 (14.8%) TP53mut only; 2 (7.4%) KRAS+STK11; 8 (29.6%) KRAS+TP53; 3 (11%) KRAS+TP53+STK11. No associations were observed between KRAS, TP53 and STK11 status and clinico-pathological variables. OS was shorter for TP53mut compared with wild-type patients in Cox univariate analysis (p=0.006). KRAS and STK11 status did not impact OS and progression-free survival. The co-occurrence of KRAS and TP53 mutations appears to have a detrimental effect in OS (p=0.064).
Conclusion
In this cohort, KRAS, TP53, and STK11 mutations were not associated with clinico-pathological features. TP53 mutations may identify a more aggressive molecular subtype of LADC.
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-61 - EGFR Inhibitors Plus Bevacizumab Are Superior Compared to EGFR Inhibitor Monotherapy in Advanced EGFR+ NSCLC Patients with BIM Deletions (ID 2697)
09:45 - 18:00 | Author(s): Helano C. Freitas
- Abstract
Background
BIM activation is essential for EGFR-TKIs triggered apoptosis in EGFR-mutant Non-small-cell lung cancer (NSCLC). A 2903-bp germline deletion in intron 2 of the BIM gene results in generation of alternatively spliced isoforms that lack the crucial BH3 domain, impairing the apoptotic response to TKIs and conferring NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions (BIMdel).
Method
A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction (PCR) analysis and direct sequencing of DNA from tumor and peripheral blood cells (PBCs). We also assessed BIM protein expression by immunohistochemistry and BIM mRNA levels by RT-PCR. Clinical characteristics, overall survival (OS), progression-free-survival (PFS), objective response rate (ORR) and treatment-related adverse events were compared in the EGFR-TKIs versus EGFR-TKIs plus Bev groups.
Result
32 patients were included; 16 of them received EGFR-TKIs and 18 received EGFR-TKIs plus Bev. The addition of Bev resulted in a significantly higher ORR compared with TKIs alone (94% vs. 44%, p=0.0014). Median PFS was longer with the use of the combination compared with TKIs alone (11.1 vs. 7.77 months; p < 0.001). Median OS tended to be longer in the EGFR-TKIs plus Bev group than in TKIs alone (30.9 vs. 25.4 months; p = 0.06). EGFR-TKIs plus Bev was associated with more grade >3 hematological and thrombotic adverse events. The expression of BIM by immunohistochemistry did not influence PFS and OS, however when stratifying BIM mRNA levels by the median (≥2.2 vs. <2.1) allowed to find a prognostic trend in favor of those with higher BIM mRNA levels (32.2 vs. 25.2 months respectively; p = 0.058).
Conclusion
EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings.
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P2.11 - Screening and Early Detection (ID 178)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.11-12 - Sputum Liquid Biopsy Provides a Non-Invasive Modality to Assess Driver Mutations and Tumor Heterogeneity in NSCLC (ID 2348)
10:15 - 18:15 | Author(s): Helano C. Freitas
- Abstract
Background
The incidence of lung cancer has significantly increased over the last century and remains the most common cause of cancer death worldwide. Our better understanding of the tumor microenvironment and of how tumors interacts with the host systemically, combined with the recent advent of the liquid biopsy, may allow non-invasive, assessment of tumor heterogeneity and evolution. Sputum has been used for the investigation of biomarkers in lung cancer since it carries airway epithelial cells, and molecular alterations identified in sputum are most likely to reflect tumor-associated changes. Our aim is to evaluate whether the molecular alterations identified in the sputum is representative of the mutations found in the tumor.
Method
Sputum samples were prospectively collected from 30 patients with lung adenocarcinoma at AC Camargo Cancer Center, from January 2017 till November 2018. Samples were collected at the time of diagnosis for further evaluation of actionable mutations in 14 genes, including EGFR, KRAS, BRAF and NRAS. Driver mutations were detected in 16 (53%) patients in tissue biopsy (six in KRAS and 10 in EGFR), and 2 cases also had EGFR T790M detected in circulating tumor DNA (ctDNA) isolated from plasma after disease progression post EGFR-TKI.
Result
Mutations were detected in 9 out of 16 sputum samples with previously known driver mutations: 3/7 with KRAS mutation (codon 12 and 61) and 6/9 with EGFR with (four exon 19 deletions, five L858R point mutations and one exon 18 G719A). Two patients with mutant KRAS detected in their sputum, did not exhibit KRAS mutations in tissue biopsy of primary tumor. One of them had a KRAS mutation detected only in a metachronous brain metastasis. EGFR T790M mutation was detected in sputum in 1 out of two samples previously positive for T790M in plasma ctDNA. All seven sputum samples negative for mutations were derived from peripheral lesions or cases with low tumor burden.
Conclusion
As a preliminary result, analysis of driver mutations in sputum had a good correlation with tissue biopsy (60%), especially in patients with centrally located tumors and high tumor burden, and seems to reflect tumor heterogeneity.
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P2.11-28 - Late-Breaking Abstract - Clinical Potential of Sputum Hyaluronan Measurement in the Diagnosis and Prognosis of Patients with NSCLC (Now Available) (ID 2622)
10:15 - 18:15 | Author(s): Helano C. Freitas
- Abstract
Background
Lung cancer is the most frequently diagnosed and also the most lethal due to late diagnosis. Many efforts are being made to mitigate this problem. In this scenario, sputum is a potentially attractive source of biomarkers present in the extracellular matrix such as hyaluronan (HA). The aim of this study is to validate HA levels in sputum’s patients with non-small cell lung cancer (NSCLC) at the time of diagnosis and after first-line treatment evaluation response and correlate the values response rate in patients submitted to definitive treatment with chemotherapy and/or radiotherapy, progression and recurrence. We also evaluated the HA concentrations in chronic obstructive pulmonary Disease (COPD) and healthy volunteers and its impact on the screening and diagnosis of lung cancer patients.
Method
HA was examined in sputum samples of 64 NSCLC, 14 COPD patients and 15 healthy controls. All the patients and healthy controls selected underwent a sputum induction.The levels of HA were measured in ng/ug of protein by a noncompetitive ELISA-like fluorometric assay.
Result
A significant different concentration pattern of HA in the sputum was found among NSCLC (median: 33.25 ng/mg), COPD (median:16.6ng/ug) and healthy individuals (median: 12.2 ng/ug), (p<0.001, Fig. 1A), as well as NSCLC before first-line treatment (median:33.25ng/mg) and after 6 months treatment regimens with good response (median:6.2ng/ug), (p<0.001, Fig 2).
Conclusion
Based on the results obtained so far, we rely on the clinical potential of sputum as a screening tool in the early detection of lung cancer.
Fig. 1A
Fig. 2
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-59 - Osimertinib in EGFR T790M Advanced NSCLC: Analysis of Uncommon/Complex EGFR Mutations in a Real-World Study (ASTRIS) (ID 1263)
10:15 - 18:15 | Author(s): Helano C. Freitas
- Abstract
Background
The challenges of treating uncommon/complex EGFR mutations impact treatment decisions in clinical practice. Osimertinib is a third-generation, irreversible, oral EGFR-TKI that potently and selectively inhibits both EGFR-TKI sensitising (EGFRm) and EGFR T790M mutations and has demonstrated efficacy in NSCLC CNS metastases. ASTRIS is an ongoing, international, real-world study of osimertinib in EGFR T790M positive advanced NSCLC (NCT02474355). We report a subset-analysis of patients with uncommon/complex mutations.
Method
Patients with stage IIIB/IV T790M positive NSCLC previously treated with an EGFR-TKI were enrolled and received osimertinib 80 mg once-daily. Progression-free survival (PFS), clinical response and time to treatment discontinuation (TTD) were analysed in both full analysis set (FAS) and patients with uncommon/complex EGFR mutations. Uncommon mutation combinations included: T790M+G719X, T790M+S768I, T790M+ex20ins; complex mutations included T790M+two or more mutation(s).
Result
From 18 September 2015 to 15 October 2018 data cut-off, 3015 patients across 16 countries had received ≥1 dose of osimertinib (FAS), 53(2%) of these patients had uncommon/complex EGFR mutations. Baseline demographics between this patient subset and the FAS were similar (Asian: 55%/69%; female: 57%/64%; median age: 59 [30–80] years/62 [range, 27–92]; WHO performance status 2: 9%/11%, respectively). Baseline EGFR mutation status at enrolment of the FAS is shown in Table 1. Clinical outcomes appeared to be lower in the uncommon/complex mutation subset than in the FAS: response rate (measured in a FAS subset with ≥1 documented response assessment) was 50% [95% CI, 35.2, 64.8] in the uncommon/complex mutation group, and 57% [55.2, 58.9] in the FAS; median PFS was 8.1 [5.4, 10.1] and 11.1 [11.0, 12.0] months; median TTD was 9.0 [6.7, 11.5] and 13.5 [12.6, 13.9] months, respectively. Overall survival data are immature.
Conclusion
Whilst clinical outcomes appeared to be lower in the uncommon/complex mutation subset than the FAS, they were favourable and support use of osimertinib 80mg in this heterogeneous population.
