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Jeffrey Crawford
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MA 08 - Supportive Care and Communication (ID 669)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Nursing/Palliative Care/Ethics
- Presentations: 2
- Moderators:E. Esposito-Nguyen, John McPhelim
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 511 + 512
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MA 08.04 - Discussant - MA 08.01, MA 08.02, MA 08.03 (ID 10859)
11:15 - 11:30 | Presenting Author(s): Jeffrey Crawford
- Abstract
- Presentation
Abstract not provided
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MA 08.11 - Do Patients Treated with Chemotherapy for Advanced NSCLC Regret Having Received Treatment? A Prospective Evaluation in 164 Patients (ID 10241)
12:10 - 12:15 | Author(s): Jeffrey Crawford
- Abstract
- Presentation
Background:
While many thousands of patients per year receive chemotherapy for advanced NSCLC with first-line or subsequent chemotherapy, little is known about patients’ views on their decision to receive that treatment. In that median survival results generally do not exceed one year, there are many potential risks for regret. Given the highly symptomatic nature of NSCLC coupled with patient, family and oncologist desires to decide rapidly on treatment, many challenges exist affecting quality decision making for patients and their supporters facing treatment. Among 59 studies dealing with regret in a recent systematic review (Becerra Perez 2016), none analyzed patients with lung cancer (66% of studies were in oncology). A clinical profile of the extent of regret, and factors contributing to that regret is lacking in those undergoing chemotherapy for lung cancer.
Method:
All patients were entered into a phase III, two-arm, prospective, randomized trial in patients receiving chemotherapy for lung cancer. Patients were randomly assigned to either usual care (UC), or enhanced care (EC) using the DecisionKEYS decision aid coupled with every 3 week PRO assessment using the electronic LCSS measure. All patients were offered the Decision Regret Scale (“DRS,” O’Connor 1999), at 11 weeks (+/- 2 weeks) after starting treatment. The DRS is a categorical scale with 5-items in 5 categories (ranging from “strongly disagree” to “strongly agree”). Patients completed assessment for decisional conflict; the patients’ supporters completed similar measures.
Result:
164 patients were entered, 160 received chemotherapy. Characteristics: 43% women; 92% Stage IV; 73% first-line therapy. Means: age 63; KPS 81. ECOG 1 = 56%; ECOG 2 = 42%. 46% represented minority groups. 22 different chemotherapy regimens were used. First-line patients received combination regimens with the majority being platinum-based with 2 or 3 drugs. 128 patients (80%) completed the DRS. Results combined the two top categories indicating the greatest extent of regret. Only 9 patients (7%) expressed regret as the maximum of the 5 DRS questions. 94% expressed that the decision for chemotherapy was a wise one. This low degree of regret did not differ by first-line or subsequent chemo or by EC versus UC groups.
Conclusion:
Patients receiving chemotherapy for advanced NSCLC, at 3 months after starting treatment, rarely (7%) have regret, and 98% expressed that they made the right decision. Other factors associated with the few patients with regret, such as decisional conflict or reduced quality of life, will also be presented. Support: NIH/NCI R01 CA-157409
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MA 19 - Mesothelioma: Bench to Bedside (ID 680)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Mesothelioma
- Presentations: 1
- Moderators:Dean A Fennell, Hedy Lee Kindler
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 315
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MA 19.09 - The Role of Neoadjuvant Chemotherapy in Patients with Malignant Pleural Mesothelioma (ID 10187)
12:00 - 12:05 | Author(s): Jeffrey Crawford
- Abstract
- Presentation
Background:
The treatment of localized malignant pleural mesothelioma (MPM) involves multimodality therapy, however, there is no standard of care with respect to operative procedure and timing of chemotherapy. We analyzed data from a single institution to identify whether the use of pemetrexed-platinum neoadjuvant chemotherapy impacts survival.
Method:
Patients with histologically-proven MPM who had surgery from 1996 to 2016 were identified. Follow-up was complete for a median of 24 months. Survival was calculated from time of diagnosis to last follow up or death. Univariate and multivariate Cox proportional hazards were used.
Result:
From 1996 to 2016 we identified 376 patients. Mean age was 66+/-8 years and 54 (14%) were female. There was no difference in survival for pleurectomy/decortication or extrapleural pneumonectomy. Neoadjuvant chemotherapy significantly improved survival compared to surgery followed by chemotherapy (table 1). Multivariate analysis was significantly associated for increased survival for epithelioid histology, T-status, node positivity, and neoadjuvant chemotherapy (table 2).Table 1. Univariate Analysis
Variable (n) Median survival (mo.) P value Gender Male (322) Female (54) 13.6 17.2 P=0.043 Histology Epithelial (252) Mixed (91) Sarcomatoid (26) 18.3 12.1 6.5 P<0.0001 T stage T 1-2 (33) T 3-4 (343) 42.6 14.3 P=0.0002 N status N 0 (129) N 1-2 (113) 23.1 11.3 P<0.0001 Neoadjuvant chemotherapy Yes (153) No (223) 19.8 11.3 P<0.0001 Table 2. Cox Proportional Hazards Model
Cox proportional hazards model including histology, t-status, n-status, and neoadjuvant chemotherapy C-index: 0.69Covariate Hazard Ratio 95% CI p-value Histology (ref: Epithelioid) Biphasic Sarcomatoid ref 1.66 4.24 [ref] [1.17-2.36] [1.77-10.1] ref 0.005 0.001 T-status 3-4 vs 1-2 3.07 [1.32-7.15] 0.009 Node-positivity 1.93 [1.40-2.66] <0.001 Neoadjuvant chemotherapy 0.65 [0.47-0.91] 0.011
Conclusion:
Our results suggest that neoadjuvant chemotherapy increases survival and likely enhances the complete resection rate. These data are being evaluated in a multi-institutional cohort of five major mesothelioma programs in North America to improve guidelines for mesothelioma therapy.
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OA 12 - Emerging Genomic Targets (ID 679)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:H. Akita, Maurice Pérol
- Coordinates: 10/18/2017, 11:00 - 12:30, F203 + F204 (Annex Hall)
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OA 12.05 - Spectrum of 1,014 Somatic BRAF Alterations Detected in Cell-Free DNA of Patients with Advanced Non-Small Cell Lung Cancer (ID 9984)
11:40 - 11:50 | Author(s): Jeffrey Crawford
- Abstract
- Presentation
Background:
Somatic BRAF V600E is a National Comprehensive Cancer Network clinical therapeutic target in non-small cell lung cancer (NSCLC), occurring in 6% of tumors from patients with lung adenocarcinoma. However, approximately half of BRAF alterations are non-V600E that do not respond to FDA-approved vemurafenib or dabrafenib. Emerging evidence suggests some non-V600E mutations exhibit clinical response to novel therapeutic agents. We analyzed the landscape of BRAF mutations in a very large cohort of patients with NSCLC who underwent somatic genomic testing utilizing a CLIA-certified/CAP-accredited/NYSDOH-approved 73 gene cell-free circulating tumor DNA (cfDNA) panel which evaluates single nucleotide variants, and selected indels, fusions, and copy number amplifications.
Method:
The Guardant Health laboratory database was queried for cfDNA tests from patients with a diagnosis of NSCLC where a BRAF variant was identified. Literature was queried for a description of the known function of non-V600E BRAF mutations on serine-threonine kinase activity.
Result:
A total of 1,014 BRAF alterations were observed in 914 tests, with 234 unique alterations identified. The majority of variants were observed only once (75.6%; N=177). 43 alterations were synonymous and excluded from analysis. Plasma-detected BRAF amplification was the most common alteration, observed in 484 tests. Of the remaining variants, 33 of 190 had functional consequence reported in the literature (17.4%), 18 with gain of function or predicted gain of function, 13 with loss of function or predicted loss of function and 2 with no effect. BRAF V600E accounted for 51.1% of occurrences of variants with gain of function or predicted gain of function (N=95 occurrences). Recurrent (>10 occurrences) non-V600E gain of function mutations included G469A (13.4%; N=25 occurrences), K601E (8.0%: N = 15 occurrences), and N581S (7.0%; N=13 occurrences). Fourteen additional gain of function variants comprised the remaining 21% of occurrences. Recurrent loss of function BRAF mutations (>10 occurrences) included G466V and D594G.
Conclusion:
This is the largest reported cohort of somatic BRAF alterations in metastatic non-small cell lung cancer. Non-V600E alterations accounted for almost 50% of the gain of function variants. The spectrum of non-V600E alterations was consistent with reports from The Cancer Genome Atlas and prior published results from tissue genomic sequencing. The recurrent non-V600E variants identified in this cohort are emerging therapeutic targets with promising early clinical data. These findings advocate for more comprehensive BRAF genomic profiling and identification of patients eligible for clinical trials targeting these non-V600E classic mutations and demonstrate the ability of plasma-based cfDNA to detect these alterations.
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OA 14 - New Paradigms in Clinical Trials (ID 681)
- Event: WCLC 2017
- Type: Oral
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:Alex Adjei, Eun Kyung Cho
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 311 + 312
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OA 14.07 - Progress in Lung Squamous Cell Carcinoma from the Lung-MAP Master Protocol (S1400) Sub-Studies S1400A, S1400B, S1400C and S1400D (ID 9593)
12:05 - 12:15 | Author(s): Jeffrey Crawford
- Abstract
- Presentation
Background:
Lung-MAP (S1400) is a master umbrella protocol designed to establish genomic screening for previously treated squamous cell lung cancer patients (SqCCA), and independently evaluate targeted therapies with matching biomarkers and alternative therapies (designated non-match therapy) in patients without putative markers. The protocol opened June 16, 2014 with four biomarker-driven sub-studies and one non-match sub-study.
Method:
Eligibility stipulated advanced SqCCA, progressing after at least one prior platinum-based chemotherapy, PS 0–2, and EGFR/ALK wild-type. Tumor samples were required and analyzed for gene alterations by FoundationOne NGS assay (Foundation Medicine). The original biomarker and non-match studies were: S1400B evaluating taselisib for PI3K mutations, S1400C evaluating palbociclib for cell cycle gene alterations (CCGA), S1400D evaluating AZD4547 for FGFR mutations, S1400E evaluating rilotumumab and erlotinib for c-MET positive tumors, and S1400A evaluating durvalumab in patients with no matching biomarkers. The original design included randomization to a control arm, but was amended to a single-arm phase 2 design. The primary endpoint for each modified sub-study was response.
Result:
As of June 16, 2017 all original sub-studies have been closed to accrual; 1298 patients registered to the screening component of the trial and 486 patients have registered to a sub-study. Two new sub-studies have been launched and are currently accruing. Details of the completed sub-studies are included in the table.Sub-study Final Accrual Biomarker prevalence/% of sub-study registrations Closure Date Response to investigational therapy N (%) Status S1400A (non-match) Total: 116 Durvalumab: 78 Docetaxel: 38 NA/59% 12/18/15 Docetaxel arm closed: 4/22/15 11 (16%) Administratively closed to enable activation of new non-match study. S1400B PI3K Total: 39 taselisib: 31 Docetaxel: 8 8%/9% 12/12/16 Docetaxel arm closed: 12/18/15 1 (4%) Closed at interim futility analysis. S1400C (CCGA+) Total: 54 Palbociclib: 37 Docetaxel: 17 19%/15% 09/01/16 Docetaxel arm closed: 12/18/15 2 (6%) Closed at interim futility analysis. S1400D (FGFR+) Total: 45 AZD4547: 35 Docetaxel: 10 16%/12% 10/31/16 Docetaxel arm closed: 12/18/15 2 (7%) Closed at interim futility analysis. S1400E (MET+) Total: 9 R+E: 4 E: 5 N/A (closed too early) 11/26/2014 N/A Closed d/t discontinuation of development of rilotumumab
Conclusion:
Lung-MAP as a master genomic screening protocol has demonstrated feasibility with respect to accrual and evaluation of targeted therapies in lower prevalence patient populations. This dynamic, centralized, single-IRB platform is well positioned to efficiently assess multiple novel therapeutics for advanced SqCCA patients.
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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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P1.01-068 - Impact of Case-Based CME on Physician Performance in the Diagnosis and Management of NSCLC (ID 9431)
09:30 - 09:30 | Author(s): Jeffrey Crawford
- Abstract
Background:
Lung cancer is the leading cause of cancer-related mortality in the United States. Over the last decade an improved understanding of the pathways that drive malignancy and disease progression have fundamentally altered the NSCLC treatment paradigm. We sought to determine if participating in a case-based online educational intervention related to NSCLC diagnosis and management improved the clinical decision-making of oncologists and pathologists in the US.
Method:
Oncologists participated in an innovative online CME activity using branching logic that assessed clinical decisions in management of patients with NSCLC and provided tailored feedback. Two patient cases were presented and clinicians were assessed on answers to multiple-choice questions pre- and post- education. If first attempt answers were incorrect, clinicians received feedback and clinical consequences for their choices, and provided a second opportunity to answer. The CME activity launched May 5, 2016 and data were collected through June 6, 2016.
Result:
For oncologists (n=149), between 52% and 70% answered clinical decision questions correctly on the first attempt, while 27% to 94% of pathologists (n=44), answered correctly . After consequence-based feedback, between 12% and 41% of both oncologists and pathologists improved their decision-making. Specific improvements seen include: 20% oncologists and 23% pathologists increased their ability to identify the need to order IHC staining to identify the tumor’s histopathology 23% more oncologists and 29% more pathologists selected the most appropriate regimen for a patient with adenocarcinoma without actionable mutations after 30% of oncologists and 41% pathologists increased in their ability to select the most appropriate therapy for a patient who has progressed on a first-line regimen based on prior treatment and the PD-L1 status of their tumor
Conclusion:
This innovative, case-based CME activity using branching logic with tailored consequence-based feedback improved clinical decision-making in management of patients with NSCLC to drive learning. It is anticipated that improved clinical decisions among oncologists and pathologists in diagnosis and management of NSCLC will lead to translation in practice and better patient outcomes. Future education using a similar design could be used to translate ongoing developments in NSCLC into clinical decisions for comprehensive management of NSCLC.
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-050 - Predicting Risk of Hospitalization in Patients with NSCLC Receiving Chemotherapy Using the LCSS 3-Item Global Index (3-IGI) (ID 10313)
09:00 - 09:00 | Author(s): Jeffrey Crawford
- Abstract
Background:
A leading factor of poor treatment outcomes and cost in cancer care is hospitalization. If hospitalization risk can be accurately predicted, preventive interventions can be effectively used and treatment regimen selection may be able to be refined. Currently, oncologists do not routinely use laboratory, molecular, PRO or imaging data to predict risk of hospitalization or its prevention. Prior research demonstrated that the 3-IGI (quality of life, activities, distress) of the LCSS at baseline, predicts survival more accurately than performance status and requires only two minutes for administration.
Method:
The objective was to determine if the 3-IGI measured at baseline accurately predicts cancer-related or treatment toxicity-related hospitalization risk. PROs were prospectively evaluated in 164 patients receiving chemotherapy for advanced NSCLC using the LCSS 3-IGI, with electronic assistance (“eLCSS-QL”). Patients were followed for hospitalization over three months. Hospitalizations were characterized as cancer-related, or treatment toxicity-related.
Result:
Characteristics: 57% men; 92% Stage IV; 73% first-line therapy; mean age 63; ECOG 1/2: 56%/42%. 77 hospitalizations occurred among 53 (33%) patients. Patients were placed into 3-IGI groups based on scores at baseline by thirds (tertiles; mean 3-IGI = 188 with 0=worst, 300=best; 33[rd] percentile <162, and 67[th] percentile > 239). Baseline 3-IGI significantly predicted risk of cancer-related hospitalizations (p<0.0001), but not treatment toxicity-related hospitalizations (27%, p=0.69). The table outlines marked differences in hospitalizations associated with baseline 3-IGI groups.PERCENT OF HOSPITALIZATIONS BY 3-IGI GROUP AT BASELINE (p = 0.0001)
Additionally, in only those in the ECOG=1 group, the 3-IGI significantly identified cancer-related hospitalization risk (p=0.025).TIME FROM BASELINE: LEAST-RISK GROUP MEDIUM-RISK GROUP HIGHEST-RISK GROUP 30-DAYS 0% 18% 23% 60-DAYS 10% 20% 39% 90-DAYS 12% 27% (HR 2.7) 41% (HR 4.6)
Conclusion:
The 3-IGI of the LCSS significantly identifies risk of hospitalization in patients receiving chemotherapy for NSCLC, and is more accurate than ECOG PS. Interventions (including enhanced monitoring) focused on identifiable high risk groups is warranted to reduce hospitalization. These results may also help in appropriate regimen choice to reduce hospitalization. Such interventions could improve cancer care and reduce costs. Support: NIH/NCI R01 CA-157409
