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P. Bradbury
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MINI 05 - EGFR Mutant Lung Cancer 1 (ID 103)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:Y. Yatabe, R. Perez-Soler
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 2a-3b
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MINI05.13 - Treatment of EGFR/ALK-Driven Non-Small Cell Lung Cancer (NSCLC) Brain Metastases: Impact of First-Line Whole Brain Radiotherapy on Outcome (ID 1251)
17:55 - 18:00 | Author(s): P. Bradbury
- Abstract
- Presentation
Background:
Brain metastases (mets) in EGFR/ALK-driven NSCLC are common, and frequently pose treatment dilemmas. Effective systemic therapy with tyrosine kinase inhibitors (TKIs) controls extracranial disease in up to 70% of patients, but often radiotherapy is required for intracranial control. As whole brain radiation (WBRT) may be associated with neurocognitive toxicity, we aimed to evaluate the impact of molecularly targeted therapy and stereotactic radiotherapy (SRS) for EGFR/ALK-driven NSCLC on intracranial disease control with and without WBRT.
Methods:
This retrospective analysis included patients treated with EGFR/ALK-positive NSCLC at Princess Margaret Cancer Centre from 1998-2015, with brain mets at lung cancer diagnosis or during treatment/follow-up. Demographic data were collected from electronic patient records. Time to intracranial progression (TTIP) and overall survival (OS) were calculated from date of diagnosis of brain mets, using the cumulative incidence function and Kaplan-Meier methods respectively; differences between groups were tested with Gray’s or log-rank test.
Results:
From 1998-2015, 162 patients with brain mets from EGFR/ALK-driven NSCLC were identified: 138 in the EGFR cohort, 23 in the ALK cohort and one included in both cohorts for analysis, whose tumour carries both an EGFR mutation and ALK rearrangement. Table 1 contains clinical characteristics and treatment details. In the EGFR cohort, initial brain mets treatment consisted of systemic therapy alone in 19 patients (17 TKI, 2 chemotherapy), SRS +/- surgery in 27 patients and WBRT +/- SRS/surgery in 88 patients. 1-year intracranial progression rates were 26%, 32% and 12%, respectively, and median TTIP was 18, 16 and 40 months [p=0.12]. Median OS was 26, 27 and 34 months respectively [p=0.49]. In the ALK cohort, initial brain mets treatment consisted of systemic therapy alone in 4 patients (1 TKI, 3 chemotherapy), SRS/surgery alone for 4 patients and WBRT +/- SRS/surgery for 15 patients. 1-year intracranial progression rates were 50%, 50% and 13%, respectively, and median TTIP was 18, 14 and 69 months [p=0.028]. Median OS was 35 months, not reached and 51 months, respectively [p=0.75]. Multivariable analysis for the whole group showed that age [p=0.021], number of brain mets [p=0.012] and extracranial control [p=0.008] were significantly associated with OS, but not WBRT [p=0.61].
Conclusion:
In this cohort of patients with brain mets from EGFR/ALK-driven NSCLC, patients treated with WBRT trended to longer TTIP. Although not statistically significant, our data also show a trend towards longer survival in patients who received WBRT. These observations require further validation in this patient population.EGFR (N=139) ALK (N=24) Median Age (Range) 59(29-86) 53(31-77) Female Sex 93(67%) 15(62%) Ethnicity Asian Caucasian Other 58(42%) 63(45%) 18(13%) 7(29%) 13(54%) 4(17%) Smoking Never Smoker Former/Current Smoker Unknown 108(77%) 30(22%) 1(1%) 19(79%) 5(21%) 0 ECOG PS (Diagnosis) 0 1 2-4 66(48%) 67(48%) 6(4%) 7(29%) 14(58%) 3(13%) Brain Mets at Stage IV diagnosis 93(67%) 13(52%) Number of Brain Mets 1 2-4 5+ N/A 32(23%) 39(28%) 62(45%) 6(4%) 9(38%) 6(24%) 9(38%) 0 Symptomatic Brain Mets No Yes 78(56%) 61(44%) 16(67%) 8(33%) Initial Brain Mets treatment WBRT WBRT+SRS/Surgery SRS+/-Surgery Systemic Therapy None 71(51%) 17(12%) 27(19%) 19(14%) 5(4%) 13(54%) 3(12%) 4(17%) 4(17%) 0
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-044 - EGFR and ALK Status Influence Health Utility and Global Quality of Life Scores in Patients with Metastatic Lung Cancer (ID 1613)
09:30 - 09:30 | Author(s): P. Bradbury
- Abstract
Background:
EGFR mutations and EML4-ALK rearrangements play important roles in prognosis and response to treatment. While extending survival is a main goal of treatment, improving symptoms, well-being, and quality of life is an equally important priority.
Methods:
At Princess Margaret Cancer Centre, a cross-sectional study evaluated 224 outpatients with metastatic lung cancer who completed demographic and EQ5D-3L questionnaires generating health utility scores (HUS, 0-1) and a visual analogue scale (VAS) slider (0-100). Patients rated their ECOG performance status (0-4), and described their health over the last month from 1 (excellent) to 5 (poor). Results were correlated with clinical and demographic data. Our objective was to compare HUS and global quality of life by mutational status. Patients with EGFR mutations and ALK rearrangements were enriched through targeted enrolment, while patients with neither alteration were selected randomly from the same outpatient clinics.
Results:
94 patients (42%) had an EGFR mutation, 23 (10%) an ALK rearrangement and 107 (48%) had neither (“wildtype”) in their tumor. Participation rate was 87%. Characteristics of the populations were as expected, with higher rates of never smokers in patients with EGFR or ALK alterations (p<0.0001), greater proportion of Asians (p=0.0004), and higher proportion of adenocarcinoma (p<0.0001). Current systemic treatment differed among groups, as the majority of patients with driver mutations were receiving targeted agents at the time of assessment (77% EGFR and 65% ALK vs 7% wildtype). Conversely, wildtype patients were more likely on chemotherapy (6% vs 17% vs 38%) or not on treatment (17% vs 17% vs 47%, p<0.0001). Patients filled questionnaires on average 25 months after initial diagnosis of lung cancer. Patients with EGFR mutations (97%) or ALK rearrangements (100%) were more often ECOG performance status 0-1 at the time of diagnosis of stage IV disease than wildtype individuals (86%, p=0.02). For quality of life analysis, we regrouped the patients with EGFR/ALK alterations (n=117). Their mean HUS was better than for wildtype patients (0.80 vs 0.71, p=0.0003), their mean VAS slider was higher (66.9 vs 60.8, p=0.0381) and their mean self-rated ECOG scores was better (0.90 vs 1.26, p=0.022).
Conclusion:
In a clinical population, patients with metastatic lung cancer harboring EGFR and ALK alterations report superior HUS and global quality of life scores when compared with patients without these molecular changes, during the course of their therapy. This is reflected in higher proportion of patients on active therapy, particularly with molecularly targeted agents, and with improved self-reported performance scores. Health utility values used in economic analyses of metastatic lung cancer patients in clinical practice should be specific for different mutations.
