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Heather A Wakelee
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MA04 - Novel Approaches with IO (ID 900)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
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MA04.03 - Immunotherapy for Non-Small Cell Lung Cancers (NSCLC) with Oncogenic Driver Mutations: New Results from the Global IMMUNOTARGET Registry (ID 13187)
13:40 - 13:45 | Author(s): Heather A Wakelee
- Abstract
- Presentation
Background
Prospective data on immunotherapy for NSCLC with oncogenic driver mutations are limited. We recently reported first results from the global IMMUNOTARGET registry (Mazières, ASCO 2018). Here, we present new data for PD-L1 and mutation subgroups.
a9ded1e5ce5d75814730bb4caaf49419 Method
In 2017, we started an international retrospective registry study ("IMMUNOTARGET") for patients with advanced NSCLC, known driver mutations (KRAS, EGFR, ALK, ROS1, BRAF, HER2, MET and RET) and PD-L1 immune checkpoint inhibitor therapy. The registry is approved by University of Toulouse and Swissethics, and funded by University of Toulouse and Cantonal Hospital of Lucerne. Anonymized real-world data submitted to the coordinating center include: patient and tumor characteristics, mutation test methods and results, systemic therapy lines, immune related adverse events, best response by RECIST, survival, and tumor PD-L1 expression (optional). Statistical calculations including best response, median PFS and OS are done at University of Toulouse.
4c3880bb027f159e801041b1021e88e8 Result
In April 2018, the registry included 551 pts from Europe, USA, Israel and Australia. Patients were 50% male/female, 28% current smokers, median age 60 years (range 28-83), 85% had PS0/1. Most (73%) tumors were stage IV at diagnosis, almost all (96%) were adenocarcinomas. Molecular classification by dominant driver mutation: KRAS=271 (49%), EGFR=125 (23%), BRAF=43 (8%), MET=36 (7%), HER2=29 (5%), ALK=23 (4%), RET=16 (3%), ROS1=7 (1%), 1 (0.2%) not classified (ALK+RET+MET). Most pts received nivolumab (466) or pembrolizumab (48) and were treated with immunotherapy in second or third line (67%). The median number of cycles was 5 (range 1-68). Fifty (11%) pts had grade 3-5 toxicity. Median OS from start of immunotherapy was 13.3 months, median PFS was 2.8 months. Best response was PR/CR in: KRAS=26%, BRAF=24%, ROS1=17%, MET=16%, EGFR=12%, HER2=7%, RET=6%, ALK=0%. Percentage of PD-L1 positive cells was available for 177 pts: 0%=71 (40%), 1-49%=46 (26%), 50-100%=60 (34%). Median % of positive cells was highest for ROS1 (90%), BRAF (50%), MET (30%) and RET (26%) mutant tumors. PD-L1 positivity was predictive for improved PFS in KRAS and EGFR mutant tumors. PD-L1 status was known in 18 tumors with ALK, ROS1 or RET rearrangements: 5 had 0%, 4 had 1-49% and 9 had 50%-100%. No tumor remissions were observed in this subgroup. The registry remains open, updated results will be presented at the conference.
8eea62084ca7e541d918e823422bd82e Conclusion
Although response rates were lower than in KRAS mutant NSCLC, individual tumors with other driver mutations responded to immunotherapy. PD-L1 expression may not accurately predict clinical benefit from immunotherapy in some molecular subgroups, better markers are needed.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MA18 - Modelling, Decision-Making and Population-Based Outcomes (ID 920)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 201 F
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MA18.10 - Evolving Immunotherapy Practice Patterns in Advanced NSCLC: Analysis of an Online Treatment Decision Tool (ID 13848)
14:30 - 14:35 | Author(s): Heather A Wakelee
- Abstract
- Presentation
Background
Checkpoint immunotherapy (IO) is revolutionizing NSCLC therapy. We have previously published results of an online decision support tool designed to provide clinicians with education and expert guidance (Chow et al: JTO 2015). Here we report an analysis of a recently updated version of this online tool, capturing the impact of emerging IO options.
a9ded1e5ce5d75814730bb4caaf49419 Method
From June 2016 to July 2017, the NSCLC decision tool was updated to incorporate new treatment options for 280 different case scenarios. Briefly, oncologists entered patient and disease characteristics and then their planned treatment into the tool. Afterwards recommendations from 5 lung cancer experts were provided for that specific patient scenario.
4c3880bb027f159e801041b1021e88e8 Result
This analysis includes 1481 individual cases entered by 863 practicing oncologists between June 2016 and April 2018 (USA 19%, Europe 33%, Rest of World 48%). During this time, treatment choices for EGFR and ALK cancers by oncologists closely resemble those of experts. After approval of 1st-line pembrolizumab for patients with high PD-L1 expression, oncologists recommended pembrolizumab less often than experts (67% vs 95%). In the 2nd-line setting following platinum chemotherapy, both tumor histology and PD-L1 expression level impacted treatment recommendations (see Table). For PD-L1 expression < 1%, recommendations between oncologists and experts differed substantially.
Second-line setting after platinum chemotherapy Participants' Treatment Choice Experts' Treatment Choice 2016 2017 2016 2017 Nonsquamous PD-L1 (≥ 1%) 54% IO
34% CT
(n = 35)
79% IO
15% CT
(n = 47)100% IO
85% IO
15% CT
PD-L1 (< 1%) 28% IO
65% CT
(n = 104)49% IO
41% CT
(n = 63)40% IO
55% CT
75% IO
25% CT
Squamous PD-L1 (≥ 1%) 62% IO
25% CT
(n = 24)74% IO
4% CT
(n = 23)100% IO
100% IO
PD-L1 (< 1%) 28% IO
65% CT
(n = 74)
38% IO
40% CT
(n = 45)
85% IO
15% CT
80% IO
20% CT
8eea62084ca7e541d918e823422bd82e Conclusion
This updated analysis of an online NSCLC decision-making tool integrates recent changes to the treatment landscape in 2017, capturing emerging patterns in IO therapy. Compared to earlier versions, practicing oncologist’s choice of 1st-line EGFR- and ALK- targeted therapy more closely tracked with experts during this period, while selection of IO differs from expert recommendations. A detailed analysis of expert versus online user data will be presented.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MTE19 - How I Treat Advanced Stage Thymic Malignancy Patients (Ticketed Session) (ID 826)
- Event: WCLC 2018
- Type: Meet the Expert Session
- Track: Thymoma/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 07:00 - 08:00, Room 205 AC
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MTE19.01 - How I Treat Advanced Stage Thymic Malignancy Patients (ID 11574)
07:00 - 08:00 | Presenting Author(s): Heather A Wakelee
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-71 - Co-Mutations, Natural History, and Outcomes of BRAF-Mutated Non-Small Cell Lung Cancer at a Single Academic Cancer Center (ID 12392)
16:45 - 18:00 | Author(s): Heather A Wakelee
- Abstract
Background
Mutations in the BRAF oncogene occur in 2-4% of cases of non-small cell lung cancer (NSCLC). Based on recent trials, combination therapy targeting BRAF and MEK within the MAPK pathway is now approved for BRAF V600E-mutated NSCLC. As BRAF mutations occur infrequently, however, the natural disease history of BRAF-mutated NSCLC remains an area of ongoing study. Our aim was to describe the natural history and outcomes of patients with BRAF-mutated NSCLC seen at our institution.
a9ded1e5ce5d75814730bb4caaf49419 Method
An IRB-approved protocol was used to query the Stanford Cancer Registry and Stanford Cancer Institute Research Database (SCIRDB) for patients with BRAF-mutated NSCLC presenting between January 1, 2006 and July 31, 2015. Each patient chart was then retrospectively reviewed.
4c3880bb027f159e801041b1021e88e8 Result
The cohort included 18 patients (median age 66.5 years, 72% male). V600E mutations were most common (72%; 13/18) while non-V600E mutations included G469A (n = 2), G466V, K601E, and V600_W604delinsR. Most patients (69%; 9/13) with V600E mutations were light or never smokers whereas most patients with non-V600E mutations (80%; 4/5) were heavy smokers (>15 pack-years). Secondary mutations occurred most commonly in TP53 (28%; 5/18). With respect to treatment, no patients received BRAF-targeted therapy upfront. Median duration of first-line platinum-based chemotherapy was 9 months (range 1.5-21.5). In the second-line setting, median duration of chemotherapy was 6 months (range 1-52) and median duration of BRAF-targeted therapy was 5.5 months (range 5.5-6.5). Median overall survival of the entire cohort was 34.8 months. Median survival from the onset of metastases (n = 16) was 26.8 months (range 2-130.5) (Table). Among patients diagnosed with stage III-IV disease, survival at 2-years was 53%, with many showing slow progression and control of oligometastatic or intrathoracic disease with systemic therapy or localized radiation.
Stage BRAF Mutation Co-occurring Mutations Overall Survival (months) Post-Metastases Survival (months) 1 IA V600E None 83.5+ 39.5+ 2 IIIB V600E None 8.5 7 3 IV G469A None 37 37 4 IIIB V600E None 40+ 26.5+ 5 IIIA G469A TP53 41 27 6 IV V600E None 14 14 7 IV V600E None 130.5 130.5 8 IIA V600E None 65 NA 9 IV V600E CTNNB1 2 2 10 IV V600E PIK3CA 47.5 47.5 11 IIIA G466V Multiple (incl. TP53) 39.5 32.5 12 IA V600E TP53 32.5+ NA 13 IV V600_W604 None 22.5 22.5 14 IV V600E None 28 28 15 IV V600E Multiple (incl. TP53) 13.5 13.5 16 IV V600E None 88.5 88.5 17 IV K601E TP53 6.5 6.5 18 IV V600E NKX2-1 19.5 19.5
8eea62084ca7e541d918e823422bd82e Conclusion
BRAF-mutated NSCLC can be associated with prolonged survival in some patients. Future research should aim to identify factors predicting longer outcomes.
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P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.04-20 - Computational Biological Model Prediction of PD-L1 Expression and Immunotherapy Response for KRAS Mutated Lung Cancer Based on Co-Mutations (ID 13049)
16:45 - 18:00 | Author(s): Heather A Wakelee
- Abstract
Background
Emerging data suggest that KRAS mutated non-small cell lung cancer (NSCLC) is a heterogeneous disease based on the presence of co-mutations. These co-mutations may impact PD-L1 expression, a predictive biomarker for PD-1/PD-L1 immunotherapy, and may result in differential responses to immunotherapy.
a9ded1e5ce5d75814730bb4caaf49419 Method
Genomic information of NSCLC patients, including 2888 from publically available datasets and 86 from Stanford University, was input into computational biological model (CBM) software (Cellworks Group, San Jose, CA). Customized computational protein network maps of disease characteristics were generated for each patient. CBM was used to predict PD-L1 protein expression and also response to PD-1/PD-L1 immunotherapy in KRAS co-mutation subsets using 3 key metrics: PD-L1 expression; Dendritic Cell Infiltration Index (9 chemokine markers); and Immunosuppressive Biomarker Expression (14 markers).
4c3880bb027f159e801041b1021e88e8 Result
The major co-mutations observed with the KRAS mutation were in tumor suppressor genes (TP53, STK11, CDKN2A, KEAP1) and a downstream effector (PIK3CA). Using the CBM approach, KRAS mutated NSCLC tumors with TP53 co-mutations had the highest prevalence of PD-L1 protein expression whereas tumors with KRAS/KEAP1 and KRAS/STK11/KEAP1 co-mutations were associated with the lowest expression. Expression of PD-L1 in tumors with KRAS/STK11, KRAS/CDKN2A, KRAS/PIK3CA co-mutations, and KRAS without co-mutations was higher than in tumors with KRAS/STK11/KEAP1 and KRAS/KEAP1 co-mutations. Of the 30 NSCLC tumors in the Stanford dataset with available PD-L1 immunohistochemistry results, including 19 with KRAS/TP53 and 11 with KRAS/KEAP1 or KRAS/STK11/KEAP1, CBM accurately predicted PD-L1 expression in these two groups at rates of 79% and 72%, respectively. In regards to prediction of response to PD-1/PD-L1 immunotherapy, CBM predicted the majority of patients with KRAS/KEAP1 and KRAS/STK11/KEAP1 to be non-responders, whereas CBM predicted the majority of patients with KRAS/TP53, KRAS/PI3KCA, and KRAS without co-mutations to be responders. The proposed mechanism for KRAS co-mutations’ impact on PD-L1 expression from the CBM model integrates differential activation of (i) downstream pathways of KRAS (PI3K/AKT, RAF/ERK, and RAL) and (ii) transcription factors involved in PD-L1 expression (i.e., MYC, HIF1α, NFKβ, AP1, and STAT1/3).
8eea62084ca7e541d918e823422bd82e Conclusion
KRAS mutated NSCLC is emerging as a diverse disease based on co-mutations. The CBM approach demonstrates that PD-L1 expression varies among KRAS co-mutation subtypes along with likelihood of response to PD-1/PD-L1 immunotherapy. CBM provides proposed mechanisms underlying these differences and therefore, provides further rationale to examine more precise delivery of immunotherapy.
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P1.11 - Screening and Early Detection (Not CME Accredited Session) (ID 943)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.11-05 - Metabolomic Profiling for Second Primary Lung Cancer Among Lung Cancer Survivors (ID 13995)
16:45 - 18:00 | Author(s): Heather A Wakelee
- Abstract
Background
Survivors of lung cancer(LC) have a high risk of developing second primary lung cancer(SPLC), the incidence of which is 4-6 times higher than that of initial primary lung cancer(IPLC). While national lung screening guidelines have been established for IPLC, no consensus guidelines exist for LC survivors. Furthermore, the factors that contribute to SPLC risk have not yet been established. The purpose of this study is to examine the potential of metabolomics to identify non-invasive blood-based biomarkers for SPLC screening.
a9ded1e5ce5d75814730bb4caaf49419 Method
We applied an untargeted metabolomics approach based on a liquid chromatography-tandem mass spectroscopy(UPLC-MS/MS) method to discover metabolic biomarkers using blood serum samples from the Boston Lung Cancer Study. Our study cohort consisted of 177 subjects diagnosed with IPLC between 1992 and 2012 and who survived >=5 years after the initial diagnosis. The cohort included 82 SPLC cases and 95 matched controls (i.e. IPLC patients without SPLC as of Dec, 2017) based on the age of initial diagnosis, sex, race, and smoking status. We applied random forest and Welch’s t-test to identify metabolomic features associated with SPLC risk and to build a risk prediction model.
4c3880bb027f159e801041b1021e88e8 Result
Our analysis detected 1008 named and 316 unnamed metabolites. The metabolites that were statistically significantly associated with SPLC risk (False Discovery Rate q-value<0.05) included 5-methylthioadenosine (MTA), phenylacetylglutamine, and umbelliferone sulfate, which showed 1.4-3.8 fold increases among SPLC cases versus controls (Figure 1). These metabolites were involved in amino acid, peptide, and xenobiotics pathways. The stratification by quintiles of estimated risk using the prediction model based on the metabolites showed that the observed incidence of SPLC was significantly higher in the fifth quintile(69.4%) versus the first-quintile(36.1%;P<0.05).
8eea62084ca7e541d918e823422bd82e Conclusion
We identified potential metabolic biomarkers for SPLC among LC survivors. A risk-stratification approach based on metabolic biomarkers can be potentially useful for identifying high-risk LC survivors to be screened by CT.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.13-02 - eXalt3: Phase 3 Randomized Study Comparing Ensartinib to Crizotinib in Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer Patients (ID 13294)
16:45 - 18:00 | Author(s): Heather A Wakelee
- Abstract
Background
Ensartinib (X-396) is a novel, potent ALK small molecule tyrosine kinase inhibitor (TKI). It is well-tolerated and has shown promising activity in NSCLC patients in a phase 1/2 study in patients that were both ALK TKI naïve and patients that received prior crizotinib, as well as those with CNS metastases. The safety profile of ensartinib appears to be different from other ALK TKIs.
a9ded1e5ce5d75814730bb4caaf49419 Method
In this global, phase 3, open-label, randomized study, approximately 270 patients with ALK+ NSCLC who have received no prior ALK TKI and up to one prior chemotherapy regimen will be randomized with stratification by prior chemotherapy (0/1), performance status (0-1/2), brain metastases at screening (absence/presence), and geographic region (Asia /other), to receive oral ensartinib (225 mg, once daily) or crizotinib (250mg, twice daily) until disease progression or intolerable toxicity.
Eligibility also includes patients ≥ 18 years of age, stage IIIB or IV ALK+ NSCLC. Patients are required to have measurable disease per RECIST 1.1, adequate organ function, and an ECOG PS of ≤2. Adequate tumor tissue (archival or fresh biopsy) must be available for central testing. The primary endpoint is progression-free survival assessed by independent radiology review based on RECIST v. 1.1 criteria. Secondary efficacy endpoints include overall survival, response rates (overall and central nervous system [CNS]), PFS by investigator assessment, time to response, duration of response, and time to CNS progression. The study has > 80% power to detect a superior effect of ensartinib over crizotinib in PFS at a 2-sided alpha level of 0.05.
Phase 3 recruitment began in June, 2016 and currently has 98 active sites in 21 countries. The duration of recruitment will be approximately 28 months. This study is registered with ClinicalTrials.Gov as NCT02767804.
4c3880bb027f159e801041b1021e88e8 Result
Section not applicable
8eea62084ca7e541d918e823422bd82e Conclusion
Section not applicable
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P1.13-03 - Ensartinib Treatment Beyond Disease Progression in Stage IV ALK+ Non-Small Cell Lung Cancer (ID 13293)
16:45 - 18:00 | Author(s): Heather A Wakelee
- Abstract
Background
Anaplastic Lymphoma Kinase (ALK) positive non-small cell lung cancer (NSCLC) patients (pts) benefit from receiving ALK tyrosine kinase inhibitors (TKIs); however, despite initial activity, resistance invariably develops. Disease progression (PD) is sometimes limited to progression which occurs in only one or a few sites and may not occur systemically. Local treatment with radiation while continuing treatment with ensartinib may enable prolonged benefit beyond progression.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients who were ALK TKI naïve or had received prior ALK treatment received ensartinib 225mg QD until PD or unacceptable toxicity or investigator discretion. The primary endpoint was safety and tolerability, and the secondary endpoint was pharmacokinetic and preliminary biological activity. Tumor assessment was performed locally every 8 weeks. Post-progression treatment with ensartinib was allowed if the investigator felt the patient was still receiving benefit from ensartinib. Cycles were approximately every 28 days, and radiation therapy after Cycle 1 for isolated CNS metastases was permitted if there was no evidence of progressive disease elsewhere. Post-progression treatment data were captured and analyzed.
4c3880bb027f159e801041b1021e88e8 Result
As of the data cut-off (May 01, 2018), 12 pts with progression continued ensartinib treatment post progression (67% with progression only in the CNS, 75% of which had CNS lesions at baseline and 33% with progression only outside the CNS). Of the 12 pts, half of the patients were ALK TKI naïve and half had received at least one prior ALK TKI. Six pts received radiation therapy at the time of initial progression. The initial median Progression Free Survival (PFS) of the 12 pts with post progression treatment was 15.7 months and median secondary PFS (date of initial progression to the date of second progression or end of treatment) was 5.7 months for a combined duration of therapy of 23.8 months. A significantly longer duration of continued therapy was observed in patients who received radiation treatment than those who did not 8.6 mos vs 3.5 mos. The secondary PFS was longer in treatment naïve pts than in pts who received a prior ALK TKI, 7.7 mos vs 5 mos. After the initial progression, excluding lesions treated with radiation therapy, secondary stable disease was observed in 92% of patients. No new or additional safety risk was identified in the pts post progression.
8eea62084ca7e541d918e823422bd82e Conclusion
Ensartinib may have clinical benefit in selected patients with NSCLC if continued post-progression. Secondary PFS was longer in patients treated with radiation therapy. Ensartinib was generally well tolerated in these patients treated post progression.
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P1.14 - Thymoma/Other Thoracic Malignancies (Not CME Accredited Session) (ID 946)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.14-17 - Identification of Molecular Subtypes of Thymic Epithelial Tumors and Novel Treatments Using a Computational Biological Model (ID 12521)
16:45 - 18:00 | Author(s): Heather A Wakelee
- Abstract
Background
The histologic classification of thymic epithelial tumors (TETs) is based on the description of both epithelial cell morphology and relative abundance of lymphocytes. Here, we used a computational biological model (CBM) approach on The Cancer Genome Atlas (TCGA) dataset to identify molecular subtypes of TETs and associated predicted therapeutic options.
a9ded1e5ce5d75814730bb4caaf49419 Method
Whole exome sequencing and gene expression data from the TCGA TET dataset (n = 102) along with the IUTAB-1 cell line was input into CBM software (Cellworks Group, San Jose, CA) to build an unsupervised classification model beyond molecular subtypes previously reported (Loehrer PJ ASCO 2017). The CBM generated a disease specific protein network map using PubMed and other online resources. Using computer simulation, disease biomarkers unique to each tumor were identified within the protein network maps. Among the tumors simulated, 6 molecular clusters were identified (TH1-TH6). The CBM digital drug library was tested against these molecular subtypes and the cell growth score (i.e. cell proliferation, viability, and apoptosis) was analyzed.
4c3880bb027f159e801041b1021e88e8 Result
The CBM identified 6 molecular subtypes among 102 TET patients. Among subtypes with a GTF2I mutation, TH1, TH4, and TH6 also had chromosomal aberrations in chromosome 22 and 9. Deletion of chromosome 22 was present in TH1, deletion of chromosome 9 in TH4 and TH6, and also amplification of chromosome 22q in TH4. Among GTF2I wild type subtypes, chromosome 22q deletion and complex cytogenetics were present in TH2, trisomy of chromosome 1 in TH3, and HRAS mutations and chromosome 2 amplification in TH5. The IUTAB-1 cell line had a GTF2I mutation and mapped to the TH4 molecular subtype. The CBM predictions of sensitivity of TH4 subtype to Nelfinavir (AKT inhibitor) and Panobinostat (histone deacetylase inhibitor) along with resistance to Everolimus (MTOR inhibitor) were validated in vitro. There were two molecular subtypes for which Everolimus was predicted to be sensitive, TH1 and TH6.
8eea62084ca7e541d918e823422bd82e Conclusion
We present an updated classification of TETs based on a CBM approach and associated potential novel therapeutic options that could be further validated in clinical trials.
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P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.16-05 - Effect of Induction Chemotherapy in the PACIFIC Study (ID 13864)
16:45 - 18:00 | Author(s): Heather A Wakelee
- Abstract
Background
The Phase 3 PACIFIC study of patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy (cCRT) demonstrated significantly longer PFS with durvalumab versus placebo (stratified HR 0.52; 95% CI 0.42–0.65; P<0.0001). Overall, 26% and 29% in the durvalumab and placebo groups, respectively, received induction chemotherapy (ICT) before cCRT. Here, we report exploratory analyses of baseline characteristics, disposition, and outcomes from this study based on the presence or absence of prior ICT.
a9ded1e5ce5d75814730bb4caaf49419 Method
PACIFIC (NCT02125461) was a Phase 3, randomized, double-blind study of patients with WHO PS 0/1 and any tumor PD-L1 status without progression after ≥2 cycles of platinum-based cCRT. Patients were stratified by age, sex and smoking history and randomized (2:1) to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months. Co-primary endpoints were PFS (blinded independent central review, RECIST v1.1) and overall survival (not available). We investigated associations between the presence/absence of ICT and disposition, baseline characteristics, and efficacy and safety endpoints.
4c3880bb027f159e801041b1021e88e8 Result
As of February 13, 2017, 713 patients were randomized; 27% had prior ICT. Baseline characteristics were similar between treatment arms; however, patients with ICT were generally younger, less frequently Asian, had lower incidence of squamous histology, and more often had stage IIIB disease. There were no differences between groups in terms of prior RT dose. PFS benefit with durvalumab was demonstrated irrespective of ICT use (ICT: HR=0.61, 95% CI, 0.41–0.88; no ICT: HR=0.54, 95% CI, 0.42–0.69). Similarly, ORR with durvalumab was numerically higher than with placebo irrespective of ICT use (ICT: 16.1% vs 13.1%; no ICT: 32.9% vs 17.1%). ICT did not affect treatment duration for durvalumab or placebo. Between-treatment safety differences were minimal across subgroups; however, patients with ICT experienced fewer SAEs, treatment-related SAEs and pneumonitis/radiation pneumonitis regardless of treatment arm.
8eea62084ca7e541d918e823422bd82e Conclusion
Durvalumab demonstrated clinical benefit irrespective of ICT. The safety profile of durvalumab was consistent in patients with or without ICT. A lower rate of toxicity was observed in patients with ICT regardless of treatment arm.
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