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D. Patel
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-008 - The Impact of Brain Metastases and Their Treatment on Health Utility Scores in Molecular Subsets of Lung Cancer Patients (ID 4348)
14:30 - 14:30 | Author(s): D. Patel
- Abstract
Background:
New therapies, particularly in advanced patients with EGFR-mutated and ALK-rearranged tumors, result in prolonged survival. Brain metastases and/or their treatment, may have a negative impact on health-related quality of life. Technological assessment of the cost-effectiveness of various treatments for brain metastases will benefit from measurements of health-related qualify of life and health utility scores (HUS). This study evaluated the impact of brain metastases on HUS across multiple health states defined on the basis on disease stability, brain-specific therapies, and molecularly-defined subsets of NSCLC.
Methods:
A longitudinal cohort study at Princess Margaret Cancer Centre evaluated 1571 EQ5D-3L-derived HUS in 476 Stage IV lung cancer outpatients, from Dec, 2014 through May, 2016: EGFR+ (n=183), ALK+ (n=38), wild-type (WT) non-squamous (n=171), squamous (n=29), and small cell lung cancer (SCLC) (n=30). Patients were stratified according to presence or absence of brain metastases at the time of assessment; mean HUS (± standard error of the mean, SEM) by presence of brain metastases and various health states and disease subtypes were reported. For patients with repeated measures, only the earliest time point was analyzed.
Results:
172 patients had brain metastases, median age 62, (range 32-86) years and 304 patients did not have brain metastases, median age 66 (29-96) years. Overall HUS was related to disease subtype but not presence of brain metastases: EGFR/ALK+ patients with (0.78±0.02) or without brain metastases (0.79±0.01) versus WT/SCC/SCLC with (0.74±0.02) and without brain metastases (0.73±0.01) (p=0.01 by subtype; p>0.10 by presence of brain metastases). However, symptomatic CNS disease (0.69±0.04) had lower HUS (versus asymptomatic disease (0.77±0.02)) (p=0.03). Patients achieving intracranial stability or response to treatment had significantly higher HUS (0.81±0.05) than patients with progressive CNS metastases (0.72±0.02) (p=0.03). Extra-cranial control also correlated with higher HUS (0.81±0.02 versus 0.69±0.03, p<0.0001). When local treatment for brain metastases was delivered within 6 months, HUS was lower (0.71±0.02 versus 0.82±0.02, p=0.0005). CNS disease treated only with systemic therapy or on no active therapy had mean HUS of 0.81±0.03, while patients treated only with stereotactic radiosurgery (SRS) had values of 0.80±0.04; there was a trend for lower HUS with whole brain radiation (WBRT) only (0.72±0.03) or WBRT+SRS (0.74±0.03) (p=0.11).
Conclusion:
Brain metastasis stability has significant impact on HUS in lung cancer patients. Treatment modalities of brain metastases may also impact HUS. Data collection is ongoing; updated HUS data including longitudinal assessments and multivariable analyses will be presented.
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P2.03b-077 - EGFR/ALK+ Patient-Derived Xenografts from Advanced NSCLC for TKI Drug Selection & Resistance Development: The REAL-PDX Study (ID 6081)
14:30 - 14:30 | Author(s): D. Patel
- Abstract
Background:
Lung cancer patient-derived xenografts (PDX) have shown to be representative models for individual patient tumors. Theoretically, such models could inform the choice of subsequent lines of therapy, since PDX development, TKI resistance induction, and subsequent drug-screening can be completed before TKI resistance develops in the patient. The goal of Resistance modeling in EGFR and ALK Lung cancer (REAL)-PDX is to develop PDX models for real-time treatment selection of subsequent lines of therapy in advanced-stage NSCLC patients.
Methods:
Since August 2015, Princess Margaret Cancer Centre patients with EGFR/ALK+, as well as lifetime never-smoking lung cancer patients with unknown mutation status, were consented to have additional tumor sampling for PDX development during routine- or trial-related biopsies. Tumor sufficiency was confirmed prior to implantation into non-obese severe combined immunodeficient (NOD-SCID) mice, with successful engraftment defined as propagation beyond first passage; unsuccessful implantations had no palpable tumor after 6 months.
Results:
72/82 (88%) approached patients consented; 49/72 (68%) had adequate tumor tissue for implantation (71% stage III/IV): 46 adenocarcinomas, 2 squamous cell carcinoma, 1 LCNEC. 36/49 (73%) were lifetime never smokers. Patients received adjuvant chemotherapy (3), TKI therapy (15), both (5), or no treatment (26) prior to sampling. Tumor samples were taken from surgically resected lung (18), metastatic adrenal (1) and brain (2), CT-guided lung biopsies (5), endoscopic ultrasound-guided (EBUS) biopsies (6), and thoracentesis pleural fluid (17) specimens. Twenty-eight implanted tumors were EGFR+ (12 exon19 deletions, 2 exon19 deletion/T790M, 1 exon19 del/exon18 mutation, 12 L858R, and 1 L858R/T790M); 7 had ALK-rearrangements, and 1 had ROS1-rearrangement. Engraftment rates of 31 assessable implanted tumors were as follows: lung resections 12/12 (100%), metastatic resections 2/3 (67%), CT- or EBUS-guided biopsies 1/5 (20%), and pleural fluid 2/11 (18%); Engraftment rate was associated with no prior treatment (14/17 no treatment vs 3/14 any treatment, p=0.001). Of 17 assessable tumors with EGFR activating mutations, 9 engrafted (53%). Of 3 assessable tumors with ALK-rearrangement, 1 was successful (33%).
Conclusion:
PDX development of EGFR/ALK+ models for testing with novel therapeutics from various tumor biopsy sites is feasible and will provide valuable real-time information for subsequent treatment decisions in advanced NSCLC patients. Updated engraftment and drug screening data will be presented.
