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D. Lawrence
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P1.01 - Poster Session with Presenters Present (ID 453)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Epidemiology/Tobacco Control and Cessation/Prevention
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.01-042 - Molecular Epidemiology of Programmed Cell Death 1-Ligand 1 (PD-L1) Protein Expression in Non-Small Cell Lung Cancer (ID 4746)
14:30 - 15:45 | Author(s): D. Lawrence
- Abstract
Background:
Expression of programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) patients might identify patients who would benefit from PD-L1 blocking antibodies. In a retrospective cohort of NSCLC patients, we characterized PD-L1 expression and other biomarkers to determine if PD-L1 expression is a prognostic biomarker and whether patient characteristics could be identified to determine those associated with high expression.
Methods:
This was a retrospective analysis of 136 NSCLC patients diagnosed between 1997 and 2015 with stage IIIB and IV disease and treated at Moffitt Cancer Center and affiliated institutions. All patients had at least 2 lines of standard of care chemotherapy and sufficient archival tumor tissue for PD-L1 testing by the Ventana SP263 validated assay and mutation status testing by targeted DNA sequencing with the TumorCare Panel. High PD-L1 expression was defined as ≥ 25% of tumor cells with membrane positivity for PD-L1 at any intensity above background staining. Statistical analyses were performed comparing PD-L1 expression by patient characteristics. Survival analyses were performed using Kaplan-Meier survival curves and the log-rank statistic. All statistical tests were two-sided; P-value of less than .05 was considered statistically significant.
Results:
Of the 136 tissues tested for PD‐L1 expression, 116 (85.3%) were collected by surgical resection and 20 (14.7%) were collected by biopsy. Mean sample age was 7.2 years (SD=2.8 years). 82 of the 136 samples also underwent targeted DNA sequencing. In this patient cohort, 51.5% were male, 83.1% were ever smokers, 90.4% were White, 39% were stage IV at time of tissue collection, 71.3% had adenocarcinoma, 28.7% had four or more lines of therapy, and 24.2% had high-expression for PD‐L1. There were no statistically significant differences with respect to PD-L1 expression for patient characteristics, overall survival (OS), or progression-free survival (PFS). Additionally, there were no statistically significant differences with respect to PD-L1 expression by EGFR (WT/PD-L1<25% = 74.4% vs. WT/PD-L1≥ 25% = 88.5%), KRAS (WT/PD-L1<25% = 74.7% vs. WT/PD-L1≥ 25% = 69.2%), and ALK status (Neg/PD-L1<25% = 98.5% vs. Neg/PD-L1≥ 25% = 100%). However, mutation load (total number of non-synonymous mutations) was statistically significantly correlated with PD-L1 expression (correlation coefficient = 0.23; P = 0.03).
Conclusion:
In this study of NSCLC patients treated with 2 or more lines of standard of care chemotherapy, PD-L1 expression (high vs. low and as a continuous covariate) was not statistically significantly associated with OS or PFS. We did observe a novel positive correlation between PD-L1 expression and mutational load.
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-031 - Impact of PD-L1 Status on Clinical Response in SELECT-1: Selumetinib + Docetaxel in KRASm Advanced NSCLC (ID 5040)
14:30 - 15:45 | Author(s): D. Lawrence
- Abstract
Background:
Anti-PD-1/PD-L1 immunotherapy has delivered clinical benefit for patients with NSCLC, and PD-L1 has emerged as a predictive biomarker. In the Phase III SELECT-1 trial (NCT01933932), selumetinib (AZD6244, ARRY-142886), an oral, potent and selective, allosteric MEK1/2 inhibitor with a short half-life, plus second-line docetaxel did not provide clinical benefit for patients with KRAS-mutant (KRASm) NSCLC compared with placebo plus docetaxel (PBO+DOC). Although no incremental benefit was observed, it is important to evaluate biomarkers, such as PD-L1, to understand more about the biology of patients with KRASm NSCLC.
Methods:
In total, 510 patients with a prospectively, centrally confirmed KRAS mutation (cobas® KRAS Mutation Test, Roche Molecular Systems) were randomised 1:1 to selumetinib 75 mg BID, plus docetaxel 75 mg/m[2] q21d (SEL+DOC), or PBO+DOC. Evaluations included progression-free survival (PFS) by investigator assessment (RECIST 1.1; primary endpoint), and overall survival (OS). Association of tumour PD-L1 status with clinical responses was assessed as an exploratory objective. PD-L1 status was centrally determined using the PD-L1 IHC 28-8 pharmDx test (Dako) for all patients with sufficient tumour sample. Samples with a pre-specified cut-off of ≥5% tumour cell staining were considered PD-L1 positive.
Results:
SEL+DOC did not improve PFS or OS compared with PBO+DOC. PD-L1 status was determined for 385 (75%) patients: 224 (58%) samples were PD-L1 <5%, and 161 (42%) samples were PD-L1 ≥5%; the remaining 125 patients had unknown PD-L1 status due to insufficient tumour sample. Subgroups were balanced across treatments. PD-L1 subgroup analysis of PFS and OS is presented below.Subgroup Events (%) in SEL+DOC group Events (%) in PBO+DOC group HR (95% CI) PFS PD-L1 <5% 94/112 (84%) 101/112 (90%) 0.89 (0.67, 1.18) PD-L1 ≥5% 65/79 (82%) 71/82 (87%) 0.70 (0.50, 0.99) PD-L1 unknown 59/63 (94%) 57/62 (92%) 1.24 (0.86, 1.79) OS PD-L1 <5% 73/112 (65%) 74/112 (66%) 0.94 (0.68, 1.30) PD-L1 ≥5% 55/79 (70%) 58/82 (71%) 0.89 (0.61, 1.28) PD-L1 unknown 48/63 (76%) 38/62 (61%) 1.57 (1.02, 2.41)
Conclusion:
Prevalence of PD-L1 positive status in this KRASm cohort was similar to that reported for a pan-NSCLC cohort (Borghaei, NEJM 2015). No significant PFS or OS differences were observed between treatments in either PD-L1 positive or negative tumours. Additional biomarker analyses are planned for different KRAS codon mutations, and LKB1 and TP53 status.
