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O.T. Brustugun
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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 | Author(s): O.T. Brustugun
- 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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P1.02 - 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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P1.02-028 - Pathways Involved in Early Stage Lung Cancers (ID 9087)
09:30 - 09:30 | Author(s): O.T. Brustugun
- Abstract
Background:
Lung cancer is a heterogeneous disease and we have few good markers of therapy prediction for chemotherapy and even immunotherapy. The biological mechanisms driving the tumour growth of different tumours even within the same histology are likely to vary and cause the diversity in therapy response. Pathifier is an algorithm developed by Eaton Domany’s group (Drier Y et al. PNAS, 2013 ) to estimate the deregulation of pathways of tumour samples based on mRNA expression levels of the genes in the pathway. Briefly, the algorithm estimates the deviation of the pathway in the tumour samples compared with normal samples. We analyse pathways deregulated in early stage squamous cell carcinomas to identify pathways potentially linked to therapy response. Such analyses have been performed for breast cancer (Livshits A et al, MolOnc, 2015), but have so far not been applied to lung carcinomas.
Method:
A total of 198 patients undergoing surgery for squamous cell lung cancer were included in the study. mRNA was extracted from the surgically resected tumour from all patients and from adjacent normal lung tissue from 22 patients. An adjustment of the pathifier algorithm was developed to avoid over-estimation of pathway deregulation. The samples were clustered according to adjusted pathway deregulation. Extensive clinical information such as mutation status, smoking history and survival was available.
Result:
Hierarchial clustering of the adjusted pathway deregulation scores identified separate clusters of squamous cell carcinomas of the lung dominated by different biological pathway with putative difference in clinical behaviour. Based on the biological activity, subgroups of patients are suggested to respond to immunotherapy and cell cycle inhibitors. The clusters are linked with survival, smoking history and expression of immune-related genes including PD-L1.
Conclusion:
Subgroups of lung squamous cell carcinomas have different biology represented by deregulation of groups of pathways. These biological differences can be used to identify clinically relevant markers of prognosis and therapy prediction. The results should be validated in functional studies.
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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): O.T. Brustugun
- 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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P2.02 - 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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P2.02-053 - The Prognostic Value of 18 Circulating Markers of Inflammation, Endothelial Activation and<br /> Extracellular Matrix Remodelling in Non-small Cell Lung Cancer Patients (ID 8302)
09:30 - 09:30 | Author(s): O.T. Brustugun
- Abstract
Background:
The aim of the study was to assess the prognostic value of 18 proteins as markers of inflammation and fibrosis (Table 1) in surgically treated non-small cell lung cancer patients and how the chronic obstructive pulmonary disease (COPD) as co-morbidity affected the prognostic significance.
Method:
Blood samples were collected from 207 lung cancer patients with an early-stage disease before surgery. 55,6% of the lung cancer group had COPD and the majority of these (86%) had moderate COPD (GOLD 2). We grouped the lung cancer patients with moderate, severe and very severe COPD (GOLD 2,3 and 4) in one group, and the lung cancer patients with mild (GOLD 1) or no COPD in another group. Serum levels of 18 proteins were measured by enzyme immunoassays. The proteins were selected because most were previously known to be associated with lung cancer and its prognosis, some with COPD.
Result:
Higher soluble tumour necrosis factor (TNF) receptor type 1 (sTNFR1) level was associated with better overall survival (OS) and progression-free survival (PFS) for lung cancer patients with COPD (OS p=0.006 and PFS p=0.030) and without COPD (OS p=0.040). High level of C-reactive protein (CRP) was significantly associated with poor overall survival regardless of COPD status. Higher osteoprotegerin (OPG) level was significantly associated with better PFS (p=0.014) and OS (p=0.027) in patients with lung cancer and COPD. In lung cancer patients with COPD, only CRP was significantly increased compared to patients without COPD of those three proteins.
Conclusion:
Whereas high levels of sTNFR1 and OPG, members of the TNF receptor superfamily, were associated with better prognosis, high level of CRP was associated with worse prognosis. This illustrates the complex role of inflammation and TNF-related molecules, particularly in the prognosis of non-small cell lung cancer, at least partly influenced by COPD as co-morbidity.
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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): O.T. Brustugun
- 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): O.T. Brustugun
- 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.
