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C. Ho
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ORAL 13 - Immunotherapy Biomarkers (ID 104)
- Event: WCLC 2015
- Type: Oral Session
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:D. Kim, D. Grunenwald
- Coordinates: 9/07/2015, 16:45 - 18:15, Four Seasons Ballroom F3+F4
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ORAL13.05 - Predictive Biomarker Testing for Programmed Cell Death 1 Inhibition in Non-Small Cell Lung Cancer (ID 1081)
17:28 - 17:39 | Author(s): C. Ho
- Abstract
- Presentation
Background:
Lung cancer is the largest cause of cancer-related mortality in the developed world. Advances in molecular targeted therapies have led to improved survival in a subset of non-small cell lung cancer (NSCLC) patients. Recently, inhibitors of the programmed cell death receptor 1 (PD1) have proven clinical efficacy in NSCLC. Only a subset of patients respond to PD1 inhibitors, likely reflecting variation in tumor-expression of the PD1 ligand (PD-L1). Many clinical trials have evaluated PD-L1 as a possible predictive biomarker for immune therapy; however several parallel and uncoordinated efforts have led to a high amount of heterogeneity, uncertainty, and ambiguity in the literature around PD-L1 and its use as a biomarker. We aim to investigate the feasibility of PD-L1 biomarker testing in NSCLC using immunohistochemistry (IHC).
Methods:
Cases of stage II, surgically resected NSCLC, adenocarcinoma were identified retrospectively from the archives of the British Columbia Cancer Agency. A tissue microarray (TMA) was constructed with matched primary and metastatic lung tumors. IHC directed towards PD-L1 was performed with 3 different primary antibody clones: E1L3N (Cell Signaling Technology), SP142 (Spring Bioscience), and 28-8 (Dako), each stain was prepared using a unique protocol. Additional cases of NSCLC with available whole-genome sequence were also stained. Staining results were reviewed and scored by intensity of staining and the percentage of positive tumor cells. Cases with positive staining of any intensity in greater than 1% of tumor cells were considered positive (H score > 1). Clinical, pathological, and genomic features of PD-L1 positive cases were reviewed.
Results:
Eighty cases of NSCLC were identified and used in TMA construction. 78 cases had matched lymph node metastases included in the TMA. 29 cases (36%) were positive by the SP142 clone, 19 (24%) by E1L3N, and 27 (34%) by the 28-8 clone. The 3 clones showed concordant results in 61 (76%) of cases, 15 (19%) discordant cases showed low level staining with SP142/28-8 and no staining with E1L3N, 2 (2.5%) cases showed no staining by 28-8 with moderate staining by SP142/E1L3N. Lymph node metastases showed a concordant PD-L1 score in 65 (83%) cases, with no detectable trend in the discordance. Comparison of primary antibodies showed a high rate of concordance (κ=0.68). Exploratory analysis of 6 additional cases with whole-genome and transcriptome data showed no statistical correlation between PD-L1 IHC and tobacco-induced hypermutation signature (p=0.22), or PD-L1 mRNA expression (R[2] = 0.35) by linear regression.
Conclusion:
PD-L1 IHC is reproducible in the setting of an academic reference laboratory. There are small, but potentially clinically relevant, differences between commercially available PD-L1 diagnostic antibodies. Primary tumor PD-L1 status is generally reflective of metastatic tumor PD-L1 status. Molecular correlates of PD-L1 positive cases remain to be elucidated and warrant further investigation.
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-005 - Early versus Late Brain Metastases in Wild Type and Mutation Positive EGFR Patients (ID 416)
09:30 - 09:30 | Author(s): C. Ho
- Abstract
Background:
Brain metastasis (BM) in NSCLC is a negative prognostic indicator. Historically, the median survival from diagnosis of BM has been reported as 6 m. The prognostic significance of BM however, may be altered in the setting of EGFR mutated disease. The timing of BM development may also influence survival outcomes. We evaluated the difference between early (<= 6 months from diagnosis) versus late (> 6 months) BM, in EGFR wild type (WT) and mutant (MT) with respect to radiographic patterns and the impact on survival.
Methods:
The British Columbia Cancer Agency provides cancer care to a population of 4.6 million. A retrospective study was conducted of referred patients with stage IV non squamous NSCLC who underwent whole brain radiotherapy and/or surgical resection of brain metastasis with known EGFR mutation status from Mar 2010 - Dec 2012. The data was analyzed by WT and MT, early and late BM groups to characterize the radiographic patterns and overall survival (OS) from initial NSCLC diagnosis (dx) and BM dx.
Results:
430 patients were identified: 327 WT patients (206 early vs 121 late) and 103 MT (65 early vs 38 late). Pattern of BM in WT early vs late showed no difference in size of largest BM, number of metastases, cerebral edema. Leptomeningeal disease was more frequent in WT late disease (2% vs 8% p=0.01). Pattern of BM in MT early vs late showed no difference in size of largest BM, cerebral edema or leptomeningeal disease. There was a trend to miliary pattern disease in MT late BM (p=0.058). Median OS from initial dx in EGFR WT was early: 7.1 m vs late: 24.9 m (p<0.001) and OS from BM dx early: 6.3 m vs late: 4.9 m (p=0.67). Median OS from initial dx in EGFR MT was early: 19.9 m vs late: 25.6 m (p=0.39) and OS from BM dx early: 19.2 m vs late: 3.9 m (p<0.001). Cox proportional hazards (CPH) model showed in the EGFR WT receipt of chemotherapy and late BM were associated with better survival. CPH in EGFR MT demonstrated that good PS and systemic treatment but not BM timing were predictive of better outcomes.
Conclusion:
Brain metastases in EGFR WT disease is a significant negative prognostic indicator with early dx associated with poor survival. In contrast, in EGFR mutation positive disease, the overall survival from diagnosis is the same regardless of the development of early or late brain metastases. This outcome may reflect the importance of systemic control and the penetrance of EGFR TKIs across the blood brain barrier.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-067 - Clinical Characteristics Associated with PDL1 Positive Status in Resected NSCLC (ID 1077)
09:30 - 09:30 | Author(s): C. Ho
- Abstract
Background:
Multiple different PD1 and PDL1 targeting antibodies have been developed for the treatment of NSCLC. Identifying the population most likely to benefit from PD1/PDL1 direct therapy has focused on PDL1 immunohistochemistry (IHC) of the tumor cells. However, each therapeutic agent has a different companion diagnostic test therefore it is difficult to consistently ascertain the PDL1 status of an individual patient. We proposed to evaluate clinical predictors of PDL1 positive status based on consensus PDL1 immunohistochemistry.
Methods:
Patients with resected Stage II lung adenocarcinoma who underwent adjuvant chemotherapy at the BC Cancer Agency were selected for this study. A tissue microarray (TMA) with matched primary and lymph node was constructed. IHC directed towards PD-L1 was performed with 2 different primary antibody clones: E1L3N (Cell Signaling Technology) and SP142 (Spring Bioscience). PDL1 consensus score was considered positive if there was concordance with both antibodies. Clinical characteristics were abstracted by retrospective chart review.
Results:
Eighty cases of NSCLC were identified and used in TMA construction. 19 primary tumors (24%) were PD-L1 positive by consensus scoring. Lymph node metastases showed a concordant PD-L1 score in 92% cases. Patients were categorized as PDL1 positive based on consensus score of the primary tumor. Baseline characteristics based on PDL1 primary tumor status negative/positive: female 64%/47%, median age 61/65 (NS). Current smoker at the time of diagnosis 34%/58% (p=0.07). The 7 EGFR mutation positive and 2 ALK positive patients were PDL1 negative. PDL1 positivity was examined by pack years of smoking: >10 pk yrs 69%/90% (p=0.13), >20 pk yrs 62%/79% (p=0.26), >30 pk yrs 39/63% (p=0.11) and tumor differentiation: well 13%/5%, moderate 48%/21%, poorly 39%/74% (p=0.03).
Conclusion:
PDL1 positive status is associated with poorly differentiated tumors and demonstrates a trend towards current smokers. This is consistent with the concept that smoking related malignancies and poorly differentiated tumors are more antigenic and therefore require immunosuppression via PDL1 to remain undetected by the immune system.
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P2.09 - Poster Session/ Nursing and Allied Professionals (ID 227)
- Event: WCLC 2015
- Type: Poster
- Track: Nursing and Allied Professionals
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.09-001 - Triage Nurse Navigator Implementation: Improvements in NSCLC Resource Utilization (ID 414)
09:30 - 09:30 | Author(s): C. Ho
- Abstract
Background:
Involvement of nurse navigators (NN) in oncology care is becoming increasingly common to facilitate more timely access to diagnostic services and treatment for patients. A lung cancer NN was implemented at the British Columbia Cancer Agency (BCCA) and this role involved developing pathways for triage and staging investigations, initiating molecular tests and coordinating new patient referrals. In the BC publicly funded health care model, reflex molecular testing is not available. The purpose was to evaluate referral practice, timelines and molecular testing for advanced NSCLC patients in cohorts with and without a triage nurse navigator.
Methods:
The study included all advanced NSCLC patients referred to the BCCA – Vancouver Centre in two separate 1 year cohorts for comparison; 2011 and 2014. Timelines between referral and systemic therapy/radiotherapy (XRT) treatments, availability of molecular testing and data on referral patterns were collected.
Results:
A total of 408 patients were included: 212 in 2011, 196 in 2014. Endpoints for medical oncology (MO) comparing 2011 to 2014: overall referral rates remained the same and the proportion of patients receiving systemic treatment increased, 57% vs 69% (p=0.05). Referral to MO consult 18 d vs 15.5 d (p=0.11), referral to systemic therapy initiation was reduced 48 d vs 38 d (p=0.016). Molecular testing: time from referral to EGFR result was reduced 34 d vs 20 d (p<0.001), EGFR results available at MO consult increased 6% vs 37% (p<0.001), rate of molecular testing increased 62% vs 91% (p<0.001), EGFR mutation positive (19% vs 26% p=0.26). For radiation oncology (RO) endpoints: RO consults 87% vs 80% (p=0.05), the same proportion of patients received XRT (91% vs 87%). Time from referral to RO consult 10 d vs 8 d (p=0.005), referral to XRT 18 d vs 11.5 d (p<0.001).
Conclusion:
Implementation of a NN at triage reduced the time period between referral and treatment for MO and RO. The proportion of patients provided with molecular testing increased and the rate of EGFR positive results remained the same, an indication that more patients received appropriate first line targeted therapy. Nurse navigator participation during triage activities suggests that physician, diagnostic and clinical resources are more appropriately allocated.
