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Negar Chooback
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 3
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-013 - CNS Metastases in EGFR Mutation Positive NSCLC: Impact on Health Resource Utilization (ID 8584)
09:30 - 09:30 | Presenting Author(s): Negar Chooback
- Abstract
Background:
EGFR mutation positive (EGFRm) NSCLC patients commonly progress in the CNS. We reviewed CNS disease development and its impact on resource utilization and outcomes in EGFRm patients who received first-line EGFR TKI.
Method:
Methods: A retrospective review was completed of all advanced EGFR+ patients referred to the BC Cancer Agency and treated with a first/second-generation EGFR TKI from 2010-2015. Baseline characteristics, systemic treatment and CNS management was collected. Comparison was made between the CNS positive (CNS+) and negative (CNS-) patients’ health resource utilization from median time of CNS+ diagnosis to death/last follow-up (8.9 m) and for no CNS metastases group, 9 months preceding death/last follow-up, using the Chi squared test and t-test.
Result:
499 patients were identified. Baseline characteristics: Female 68%, median age 66 (30-90), adenocarcinoma 89%, Asian 51%, never/former/current smoker 67/24/9%, exon 19/21/other/not specified 57/37/3/3%. 229/499 patients (46%) developed CNS+; 39% at diagnosis, 61% during the course of disease. Systemic treatment: first-line EGFR TKI 95%, first-line platinum doublet 5%; 40% (202/499) second-line EGFR TKI 24%, second -line platinum doublet 56%, single agent chemo 13%, osimertinib 7%, third-line therapy 47%. CNS+ management: surgery+/-WBXRT 13%, WBXRT alone 73%, SRS+/-WBXRT 5%, no CNS directed therapy 9%. Median time from diagnosis to CNS+ was 7.6 m. Median time from development of CNS+ diagnosis to death was 8.9 m. Median OS was 24m in CNS+ versus 33m in CNS- (p<0.001).Events in 9m preceding death or last follow-up (consistent with median time from CNS+ to death) No CNS Metastases n=270 CNS Metastases n=229 p value Average number of clinic visits 8.53 12.71 <0.001 Average number of hospitalizations 0.43 0.76 <0.001 Average number of CNS imaging investigations 0.52 2.65 <0.001 Average number of ER visits 0.03 0.14 0.001 Palliative Care Unit admission 22 (8%) 22 (10%) 0.64 Hospice admission 9 (3%) 43 (19%) <0.001
Conclusion:
The incidence of CNS+ in EGFRm patients is high and associated with increased Health Resource Utilization. Prevention or delay of CNS+ with newer systemic therapy options may result in decreased interactions with health care providers, which may translate into lower resource utilization and cost savings.
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P3.01-015 - Differential Outcomes between First and Second Generation TKIs in Patients with Activating EGFR Mutations in NSCLC (ID 8667)
09:30 - 09:30 | Author(s): Negar Chooback
- Abstract
Background:
Both first and second generation EGFR tyrosine kinase inhibitors (TKIs) have efficacy in NSCLC with activating EGFR mutations (EGFRM+). Previous studies showed a differential benefit of second generation TKIs based on mutational subtypes but failed to show a difference in overall survival (OS). We aimed to characterize the patterns of use and outcomes of first and second generation TKIs and describe any differences with mutation subtype in the real world setting.
Method:
A retrospective review of all advanced EGFRM+ NSCLC patients treated with TKIs between the years 2010-2015 at the British Columbia Cancer Agency was performed. All time to event analyses were performed from date of diagnosis of metastatic disease. Multivariate regressions were performed to examine for associations of OS, treatment and mutation subtypes.
Result:
500 patients were eligible for analysis: 283 patients had an exon 19 deletion (del19), 185 had an exon 21 L858R mutation and 32 were not specified or have mutational variants such as G719var. Patient characteristics in the del19 vs. L858R group were similar: 69%/66% were female, 66%/71% were never smokers, 90%/89% were adenocarcinoma, 20%/20% had CNS metastases at diagnosis, 85%/84% had de novo metastatic disease and 41%/37% received ≥2 lines of therapy (all p>0.05). The del19 cohort had less Asians (46% vs 58%, p=0.02) and were younger (median age 63 vs. 69, p=0.02) compared to L858R group. In the del19/L858R cohorts, 81%/19% and 84%/16% received a first and second generation TKI respectively. 43% of patients receiving a second generation TKI required a dose reduction to manage the toxicity and one patient discontinued the medication. OS in the entire cohort was 26 months, with the del19 group surviving longer compared to the L858R cohort (27 vs. 22 months, p<0.01). In multivariate analysis, factors associated with improved OS were del19 (HR0.7, p<0.01 95%CI0.6-0.9), treatment with a second generation TKI (HR0.6, p=0.01 95%CI0.5-0.9) and absence of CNS metastases (HR0.7, p<0.01 95%CI0.5-0.9). First line treatment with a second generation TKI was associated with better OS compared to a first generation TKI (HR0.6, p=0.04 95%CI0.3-1.0). This was statistically significant only in the del19 subgroup (HR0.4, p=0.04 95%CI0.2-1.0).
Conclusion:
Use of a second generation TKI in EGFRM+ advanced NSCLC is associated with improved OS in multivariate analyses controlling for other prognostic factors. This was significant in the entire group and in the del19 cohort, supporting the use of mutational subtype to guide therapy decisions.
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P3.01-030 - CNS Metastases in EGFR Mutation Positive (EGFRm) NSCLC Patients: The Prognostic Relevance of Presenting Symptoms (ID 9135)
09:30 - 09:30 | Presenting Author(s): Negar Chooback
- Abstract
Background:
The overall survival (OS) of patients with EGFR mutation positive (EGFRm) lung cancer has changed dramatically due to the combined benefit of targeted systemic therapy, local management of oligometastatic disease and incorporation of judicious use of radiotherapy. We reviewed EGFRm NSCLC patients who were diagnosed with CNS metastasis to determine the prognostic importance of the initial CNS presentation.
Method:
A retrospective review was conducted of EGFR+ referred to the BC Cancer Agency between 2010 and 2015, treated with a first/second-generation EGFR TKI who developed CNS metastases (CNSm). Baseline characteristics, presenting symptoms and CNS-targeted treatment data was collected. Cox regression was conducted to determine the prognostic implications of the most common clinical presentations on OS.
Result:
229 patients were identified; 90 presented with CNSm and 139 developed CNSm during the course of their disease. Method of CNSm detection: CT only 61%, MRI only 8%, CT and MRI 30%, PET 1%. 80% of patients were symptomatic at CNSm diagnosis. Baseline characteristics: female 66%, median age 62 (34-90), Asian 51%, exon 19/exon 21/rare mutation/not specified 56/39/3/2%. CNS management: 13% surgery+/- whole brain radiotherapy (WBRT), 73% WBRT alone, 5% stereotactic radiosurgery (SRS)+/-WBRT, 9% no CNS directed therapy. OS was 21.6 months in patients who presented with CNSm vs. 27.1 months in those who developed CNSm during the course of disease (p=0.39). On multivariate analysis, the only presenting symptom associated with increased risk of death was cognitive dysfunction.Frequency of symptom at presentation Univariate Analysis Multivariate Analysis HR P value HR P value Cognitive Dysfunction 19% 1.26 0.01 1.21 0.04 Motor Dysfunction 18% 1.04 0.69 Balance and Ataxia 11% 1.04 0.46 Cranial Nerve Changes 8% 0.94 0.65 Headache and Dizziness 30% 0.94 0.41 Nausea and Vomiting 13% 0.92 0.48 Visual Disturbance 10% 0.99 0.97 Speech and Aphasia 10% 1.19 0.16 Seizures 7% 0.75 0.09 0.78 0.13 Leptomeningeal disease 12% 1.25 0.04 1.20 0.10
Conclusion:
The most common symptoms at initial presentation of CNSm in EGFRm patients were headache and dizziness, cognitive dysfunction and motor dysfunction. In multivariate analysis, only cognitive dysfunction was associated with poorer survival. Clinicians should have a low threshold for CNS screening based on the varied clinical symptoms experienced by patients
