Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
Background: CD4 + CD25 + Foxp3 + regulatory T-cells (Tregs) are known to suppress
immune responses. Treg-mediated immunosuppression is a key mechanism for
tumor immune-evasion, which could lead cancer immunotherapies to failures.
Systemic depletion of Tregs has been tried; however, intravenously delivering
antibodies against Tregs might not sufficiently deplete Tregs in tumoradenocarcinomas)
were retrospectively evaluated for response to Nivolumab.
Pts’ samples from a subgroup of responders (14/17 pts, 82%), were further
analyzed for PD-L1/PD-1 expression by immunoistochemistry (IHC), and for
TILs density. We used rabbit monoclonal antibodies anti PD-L1 [clone E1L3N]
for tumor cell expression (0-3, negative-intense) and mouse monoclonal
antibody anti PD-1 [clone EH33] for TILs. Results: Clinico-pathologic
characteristics: mostly smoker males (81%), PS 0-1 (85%), EGFR+ 7%, K-RAS+
23%. Overall response rate was 25% (2% complete response and 23% partial
response), stable disease 30%, progressive disease 41%. Median progression
free survival (PFS) and overall survival (OS) for the entire cohort were 2.9
and 8.3 months (mo) respectively. 1 and 2-y OS rates were both 44% (95% CI,
29-58). Pts with EGFR + NSCLC showed a significantly lower median OS with
respect to the wild type cohort (4.5 vs NR; p < 0.005) as well as pts with brain
metastases (4.1 vs NR), while a trend toward improvement in PFS for K-RAS+
was seen. A subgroup analysis according to the time to progression to prior
chemotherapy regimen (< 3 mo versus > 6 mo), confirmed a poorer survival for
those with rapid spread of disease. Among laboratory tests, a better outcome
for those who developed G2 leucopenia was demostrated (OS 8.3 vs 5.0 mo).
Severe drug-related adverse events occurred in only 5.7% of pts. PD-L1, PD-1,
TIL expression for 14/17 pts with OR, were as follows: PD-L1 > 5% 6/14 pts
(43%); PD-1 2/14 (14%); focal TILs presence 7/14 (50%). Conclusion: Nivolumab
confirms activity in NSCLC with durable responses and accettable safety
profile. Of note, 44% of our patients were alive at 2 years. No predictive role
emerged in our small cohort, according PD-L1, PD-1 and TILs expression, for
those obtaining a tumor response. Interactions among alternative factors
such as smoking habit, mutational status, time to progression, bone marrow
toxicities (ie leucopenia), may have more powerful association with response
and clinical outcome. Updated clinical activity and biomarker analysis will be
presented.
Keywords: Immunotherapy, non small cell lung cancer, predictive biomarkers
POSTER SESSION 3 – P3.02C: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
IT BIOMARKERS –
WEDNESDAY, DECEMBER 7, 2016
P3.02C-069 PRETREATMENT NEUTROPHIL-TO-LYMPHOCYTE RATIO
(NLR) PREDICTS OUTCOMES WITH NIVOLUMAB IN NON-SMALL
CELL LUNG CANCER (NSCLC)
Stephen Bagley 1 , Shawn Kothari 2 , Charu Aggarwal 1 , Joshua Bauml 1 , Evan
Alley 1 , Tracey Evans 1 , John Kosteva 1 , Christine Ciunci 1 , Jeffrey Thompson 3 ,
Susan Stonehouse-Lee 1 , Victoria Sherry 1 , Elizabeth Gilbert 1 , Beth Eaby-
Sandy 1 , Faith Mutale 1 , Gloria Dilullo 1 , Roger Cohen 1 , Anil Vachani 4 , Corey
Langer 1
1 Hematology/Oncology, University of Pennsylvania, Philadelphia/PA/United States
of America, 2 Medicine, University of Chicago, Chicago/IL/United States of America,
3 Pulmonary/critical Care, University of Pennsylvania, Philadelphia/PA/United
States of America, 4 University of Pennsylvania, Philadelphia/PA/United States of
America
Background: The NLR, a marker of systemic inflammation, has been
associated with outcomes in multiple cancers. In patients (pts) with
metastatic melanoma treated with ipilimumab, pre-therapy NLR < 5 has been
associated with improved progression-free survival (PFS) and overall survival
(OS). However, the utility of NLR as a marker of outcomes in pts with NSCLC
treated with programmed-death 1 (PD-1) inhibitors is not known. Methods: We
conducted a retrospective cohort study of pts with advanced NSCLC treated
with nivolumab off clinical trials at the University of Pennsylvania between
March 2015 and March 2016. NLR was calculated from complete blood counts
obtained within two weeks of starting nivolumab. Pts were dichotomized
based on a NLR