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Simon Ekman
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MA 18 - Global Tobacco Control and Epidemiology II (ID 676)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Epidemiology/Primary Prevention/Tobacco Control and Cessation
- Presentations: 1
- Moderators:H. Kawai, Christian Klaus Manegold
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 511 + 512
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MA 18.14 - Non-Small Cell Lung Cancer (NSCLC) Treatment and Survival in Scandinavia: The SCAN-LEAF Study (ID 9295)
17:10 - 17:15 | Presenting Author(s): Simon Ekman
- Abstract
- Presentation
Background:
As the lung cancer treatment landscape evolves, it is important to understand changes in care and outcomes of patients with NSCLC. SCAN-LEAF objectives include describing NSCLC disease, treatments and health outcomes in Scandinavia (Denmark, Norway and Sweden). The present analyses examined treatment proportions and temporal trends in overall survival, drawing on national registry data.
Method:
NSCLC patients diagnosed 2005-2013 (follow-up until 2014) were included in the present analyses of this retrospective longitudinal cohort study. Patient characteristics and treatment described included demographics, disease stage at initial diagnosis [resectable: I-IIIA; locally advanced: IIIA-B (radiation therapy within 3 months); advanced: IIIB (no radiation therapy within 3 months)-IV], histology, non-drug treatment (surgery and radiation: present analyses include Norway and Sweden 2008-2014 only), and survival. Overall survival (OS) (%+95% CI) was calculated 1, 3, and 5 years post-diagnosis, by stage, and by diagnosis year.
Result:
66,012 NSCLC patients were diagnosed during 2005-2013 in Scandinavia (53.6% male, mean age 68.9 years); diagnosis stage: resectable (26%), locally advanced (15%), advanced (59%). In Norway and Sweden, surgery was performed on 58.5%, 9.9% and 1.9% of patients at resectable, locally advanced and advanced stage, respectively; radiation therapy in 28.0%, 58.0% and 30.4%, respectively. 1-yr OS gradually and significantly improved by calendar year of diagnosis for all disease stages. At 3 and 5 years post-diagnosis, OS was positively and significantly associated with calendar year of diagnosis for patients with resectable and locally advanced, but not advanced disease (Table 1).Table 1. Proportion NSCLC patients from Denmark, Norway and Sweden diagnosed during 2005-2013 who survived 1, 3 and 5 years after diagnosis, by stage and calendar year of diagnosis. Stage at diagnosis & Calendar year of diagnosis % survived 1-, 3- and 5-years after NSCLC diagnosis 1-year 3-year 5-year Resectable disease Overall 81.0% (80.4%, 81.6%) 56.8% (55.9%, 57.7%) 43.5% (42.5%, 44.6%) 2005 74.7% (72.5%, 77.0%) 51.0% (48.5%, 53.6%) 40.0% (37.4%, 42.5%) 2006 77.0% (74.8%, 79.2%) 53.3% (50.7%, 55.9%) 42.3% (39.7%, 44.8%) 2007 78.6% (76.6%, 80.7%) 55.0% (52.5%, 57.5%) 43.5% (41.1%, 46.0%) 2008 80.6% (78.6%, 82.5%) 56.4% (53.9%, 58.8%) 44.2% (41.7%, 46.7%) 2009 79.7% (77.7%, 81.7%) 57.4% (55.0%, 59.8%) 45.8% (43.3%, 48.2%) 2010 81.4% (79.6%, 83.2%) 59.1% (56.8%, 61.4%) 2011 83.1% (81.4%, 84.7%) 61.2% (59.0%, 63.4%) 2012 85.5% (84.0%, 87.0%) 2013 84.2% (82.7%, 85.8%) p-value trend <0.0001 <0.0001 0.0008 Locally advanced disease Overall 52.0% (51.0%, 53.0%) 18.4% (17.5%, 19.3%) 10.8% (9.9%, 11.6%) 2005 45.7% (42.4%, 49.0%) 13.9% (11.6%, 16.2%) 7.8% (6.1%, 9.6%) 2006 45.7% (42.3%, 49.1%) 15.4% (12.9%, 17.8%) 10.7% (8.6%, 12.9%) 2007 51.5% (48.2%, 54.7%) 18.6% (16.0%, 21.1%) 11.0% (9.0%, 13.1%) 2008 50.0% (46.7%, 53.3%) 17.0% (14.5%, 19.4%) 10.3% (8.3%, 12.3%) 2009 50.9% (47.8%, 54.0%) 19.8% (17.4%, 22.3%) 12.9% (10.8%, 15.0%) 2010 51.1% (48.1%, 54.1%) 18.9% (16.5%, 21.2%) 2011 55.9% (53.1%, 58.7%) 21.2% (18.9%, 23.5%) 2012 57.0% (54.2%, 59.9%) 2013 56.1% (53.2%, 59.0%) p-value trend <0.0001 <0.0001 0.0021 Advanced disease Overall 26.2% (25.7%, 26.6%) 6.3% (6.0%, 6.6%) 3.4% (3.2%, 3.7%) 2005 24.4% (23.1%, 25.8%) 6.3% (5.5%, 7.0%) 3.5% (2.9%, 4.1%) 2006 24.2% (22.8%, 25.5%) 6.1% (5.4%, 6.9%) 3.4% (2.8%, 4.0%) 2007 25.7% (24.4%, 27.0%) 5.9% (5.2%, 6.6%) 3.1% (2.6%, 3.7%) 2008 25.0% (23.7%, 26.3%) 6.0% (5.3%, 6.7%) 3.3% (2.8%, 3.9%) 2009 26.5% (25.0%, 28.0%) 6.9% (6.0%, 7.8%) 3.9% (3.2%, 4.5%) 2010 26.3% (24.9%, 27.7%) 7.0% (6.2%, 7.8%) 2011 27.4% (26.1%, 28.8%) 6.2% (5.4%, 6.9%) 2012 28.1% (26.7%, 29.5%) 2013 27.9% (26.6%, 29.3%) p-value trend <0.0001 0.2480 0.5359
Conclusion:
These analyses showed modest improvements in survival for patients with earlier stage disease over time. However, the majority of patients were diagnosed with advanced stage disease for which no improvement in temporal trends of survival was found, beyond one year post-diagnosis. This suggests an unmet need for effective treatments still remains, particularly for patients with advanced disease.
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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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P1.01-074 - Exosomal RNA-Profiling of Lung Pleural Effusions Identifies Adenocarcinoma Patients through Elevated miR-200 Expression (ID 8919)
09:30 - 09:30 | Author(s): Simon Ekman
- Abstract
Background:
The inherent challenges associated with lung tissue biopsies have spurred an enormous interest in the use of liquid biopsies. Pleural effusions are one such liquid biopsy which may enable lung cancer profiling and also assess if the patient suffers from a benign or malignant process in the lungs. Recently extracellular vesicles of endocytic origin, exosomes, have attracted interest as liquid biopsy of tumors since they can be used to look at tumor derived mutations as well as tumor cell activity represented by the RNA transcriptome. The RNA cargo carried in exosomes is known to resemble the RNA profile of the primary tumor. Here we aimed to analyze if microRNA and targeted cancer mRNA profiling of exosomes isolated from pleural effusions could decipher biomarkers associated with lung adenocarcinoma.
Method:
A systematic microRNA profiling of matured processed microRNAs along with targeted cancer mRNA profiling was carried out on extracellular vesicles, including exosomes, derived from 36 clinical pleural effusions, separated into 18 benign and 18 lung adenocarcinoma samples. Benign pleural effusion consisted of unspecific inflammation in the majority of cases. The two groups were well balanced with respect to age (median = 72Y) and smoking history (ever smokers in circa 70% of cases). However, males were overrepresented in the benign group (83% vs 44%). Both microRNA and mRNA profiling was conducted using TaqMan RT-qPCR Open Arrays (containing 800 genes each) followed by statistical ranking (Wilcoxon test) of differentially regulated transcripts between the two patient groups.
Result:
Systematic RNA profiling revealed a substantial, and highly significant (p<0.0001), elevated expression of all members from the extended miR-200 family in pleural effusions collected from patients with NSCLC adenocarcinoma. By cross-analyzing the obtained microRNA profiling data to the mRNA cancer panel expression, statistical enrichment between miR-200 family members and predicted miR-200 target genes, including PIK3CA, NOTCH1 and KRAS was observed (Fisher’s exact test, p=0.0105).
Conclusion:
Our study demonstrates the usage of exosomal RNA profiling from pleural effusions to define patients with lung adenocarcinoma and further highlights miR-200 microRNAs as diagnostic markers in lung cancer liquid biopsies. Acknowledgment: This study was supported from the following funding bodies: Swedish Cancer Society, Stockholm Cancer Society, Stockholm County Council, Knut and Alice Wallenberg Foundation and Erling Persson Family Foundation.
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P1.06 - Epidemiology/Primary Prevention/Tobacco Control and Cessation (ID 692)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Epidemiology/Primary Prevention/Tobacco Control and Cessation
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.06-012 - Non-Small Cell Lung Cancer (NSCLC) Patient Characteristics and Clinical Care Insights in Sweden: The SCAN-LEAF Study (ID 9537)
09:30 - 09:30 | Author(s): Simon Ekman
- Abstract
Background:
Understanding non-small cell lung cancer (NSCLC) epidemiology and outcomes is fundamental for clinical decision-making. SCAN-LEAF is a retrospective longitudinal cohort study that aims to describe NSCLC epidemiology, clinical care, and outcomes of patients in Scandinavia. The present analyses examine clinical characteristics and disease management of a subset of these patients.
Method:
Cohort 2 (EMR data from Uppsala, Stockholm sites, extracted using the Pygargus Customized Extraction Platform (CXP 3.0) and linked to registry data) consisted of NSCLC patients diagnosed 2005-2013 (follow-up until 2014). Co-morbidity burden was calculated with the Charlson Co-morbidity Index (CCI). Descriptive statistics were calculated, stratified by disease stage at diagnosis [resectable: I-IIIA; locally advanced: IIIA-B (radiation therapy within 3 months); advanced: IIIB (no radiation therapy within 3 months)-IV].
Result:
48.4% of the 3984 patients were male. At diagnosis, mean age was 68.4 years with disease stage distribution: resectable (30.4%), locally advanced (10.5%), advanced (56.3%), not specified (2.7%). CCI distribution was similar between stages, as was BMI. Smoking status: never (7.4%), former smoker (34.7%), current smoker (25.6%), unknown (32.4%). Histology: adenocarcinoma (63.3%), squamous (20.5%), NSCLC NOS (Not Otherwise Specified) (16.2%). ECOG: 0/1 (48.4%), 2/3 (13.2%), 4 (2.2%), unknown (36.2%). Metastases at diagnosis were reported for 42.4% patients. 829 patients were tested for molecular sub-type EGFR (of which 751 had a valid test result, of which 14.6% were positive for the mutation) and 267 for ALK (of which 247 had a valid test result, of which 14.6% were positive for the rearrangement). More patients with locally advanced disease were treated with radiation than patients with resectable or advanced disease [(68.8%, n=289) vs (35.9%, n=436) and (47.4%, n=1064), respectively], and a greater proportion of locally advanced patients received systemic therapy [(72.1%, n=303) vs (39.4%, n=478) and (67.1%, n=1505), respectively]. The proportion of patients not treated with surgery, radiation, or systemic therapy (based on pre-selected procedure lists) was higher for advanced (22.3%, n=500) vs resectable (6.5%, n=79) and locally advanced disease (11.9%, n=50).
Conclusion:
SCAN-LEAF EMR data provides unique insights into Scandinavian NSCLC patient populations and treatments. These data suggest unmet medical need based on majority of patients being diagnosed at advanced stage and low numbers tested for molecular subtype mutation but we expect these dynamics to change over time. Additionally, our data suggest unmet treatment need in patients with advanced disease based on a high proportion receiving no surgery, radiation, or systemic therapy, whilst acknowledging potential for misclassification and/or missing treatment data.
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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: 2
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-035 - Osimertinib in Relapsed EGFR-Mutated Non-Small Cell Lung Cancer Patients with Brain Metastases: Results from the TREM-Study (ID 9286)
09:30 - 09:30 | Author(s): Simon Ekman
- Abstract
Background:
Osimertinib, an irreversible EGFR-TKI with activity also against the resistance mutation T790M, has a high brain permeability surmising intracerebral efficacy in T790M-negative cases. We assessed the efficacy of osimertinib in T790M-positive and –negative patients.
Method:
The TREM-study is an investigator initiated phase 2, single-arm, multi-center clinical trial conducted in five Northern European countries. Patients with advanced EGFR-mutated NSCLC with progression after at least one EGFR-TKI were assigned to treatment with osimertinib 80 mg daily until radiological progression or death. Both T790M-positive and –negative patients were enrolled, as well as patients with stable and asymptomatic brain metastases. The primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints were progression free survival (PFS), duration of response (DoR), disease control rate (DCR) and overall survival (OS). We here present data from a subset of patients with brain metastases at study entry.
Result:
Of 147 included patients, 34 presented with CNS-metastases at inclusion. This subset of patients had poorer performance status at baseline than the full study cohort (31 % with ECOG 2 in the CNS-subgroup vs 17 % in the full study cohort) and the median age was lower (61.5 vs 65 years), otherwise similar to the full cohort in terms of baseline characteristics. 69 % (20/29) were T790M-positive and 31 % (9/29) negative. 5 patients had unknown T790M-status. 28 patients were evaluable for response. ORR was 39 % (11/28) and DCR 75 % (21/28). For T790M-positive patients ORR was 53 % (9/17) and DCR 88 % (15/17), in T790M-negatives 13 % (1/8) and 38 % (3/8) respectively. Median DoR in T790M-positive patients was 14.7 months (95 % CI 6.4-22.9) and 5.5 months in one T790M-negative patient. Two patients had ongoing responses after 15.9 and 17.5 months at data cutoff. Median PFS in the CNS-subgroup was 7.2 months (95 % CI 4.1-10.3 months) vs 9.7 months (6.3-13.1) in patients without CNS metastases, p=0.300, regardless of T790M-status. In the CNS-subgroup PFS in the T790M-positive patients was 10.1 months (7.9-12.3) vs 2.0 months (0.9-3.2) in the T790M-negative patients, p<0.001. Of 18 patients who had progressed at cutoff, 7 had CNS as site of progression (4 T790M-negative, 2 unknown and only one T790M-positive).
Conclusion:
Although a limited number of patients in this subgroup analysis, our results show that osimertinib has similar efficacy in patients with CNS disease as without, whereas the benefit in T790M-negative patients may be substantially lower.
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P2.03-037 - Osimertinib in Relapsed EGFR-Mutated, T790M-Negative Non-Small Cell Lung Cancer (NSCLC) Patients: Results from the TREM-Study (ID 9415)
09:30 - 09:30 | Author(s): Simon Ekman
- Abstract
Background:
The resistance mutation T790M emerges in around 60 % of EGFR-TKI treated NSCLC patients. Osimertinib is approved only in T790M-positive patients. We assessed the efficacy of osimertinib in both T790M-positive and -negative patients and here present results from T790M-negative patients.
Method:
In this investigator initiated, multicenter, single-arm, phase 2 clinical trial conducted in five Northern European countries, patients with progression on at least one previous EGFR-TKI and with measurable disease by RECIST 1.1 were assigned to treatment with 80 mg of osimertinib daily until radiological progression or death. Rebiopsy for assessment of mutational status was done after inclusion. Plasma samples were collected for translational research purposes (not analyzed yet). The primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints were progression free survival (PFS), duration of response (DoR), disease control rate (DCR) and overall survival (OS).
Result:
T790M-status was assessable in rebiopsies from 120 of 147 included patients. Of these, 42 patients (35 %) were T790M-negative in tissue. 55 % (23/42) of the T790M-negative patients had exon 19 deletion at diagnosis as opposed to 71 % of the T790M-positives, other baseline factors were similar between the two groups. ORR in the T790M-negative group was 19 % (7/36) including one patient with complete response. In the T790M-positive group, ORR was 52 % (37/71), no complete responses. DCR was 64 % (23/36) and 87 % (62/71), respectively. All responses were confirmed. Median DoR was 11.0 months (95 % CI 3.0-19.1) in the negatives and 12.0 months (8.7-15.2) in the positives, p = 0.887. In the T790M-negative group, median PFS was 5.5 months (2.6-8.3) vs 10.8 months (8.2-13.4) in the T790M-positive group, p = 0.009. Subgroup analyses were performed in the T790M-negative group and there was significant higher median PFS in patients without CNS-metastases (5.6 vs 1.6 months, p = 0.007), in patients with duration of previous TKI-treatment over median (15 months) vs under (9.7 vs 3.5 months, p = 0.044) and in patients with one previous line of TKI vs two or more lines (7.3 vs 2.0 months, p = 0.007).
Conclusion:
T790M-negative patients who respond have similar DoR as T790M-positive patients. T790M-negative patients without CNS-metastases and with durable response on first EGFR-TKI could benefit from osimertinib.
