Abstract 1291
Background
The efficacy of immunotherapy treating EGFR-positive non-small cell lung cancer (NSCLC) patients has been proved to be limited. However, a series of mutant-patients could be benefit from PD-1 blockade. Therefore, this study evaluated the immune microenvironment in NSCLC with uncommon EGFR mutation, and explored the prospect of immunotherapy in this cohort.
Methods
We retrospectively evaluated the expression of PD-L1, CD4 and CD8 in NSCLC patients who harbored uncommon EGFR mutation at Zhejiang Cancer Hospital between April 2016 and September 2017. The association with clinical factors and outcomes were also explored, as well as the effectiveness of immunotherapy in uncommon mutation-positive cases.
Results
Among the 600 NSCLC patients with EGFR mutation, we retrospectively collected 49 (8.2%) cases bearing uncommon mutation. In total, 49.0% (24/49) of NSCLC patients showed a strong PD-L1 expression in tumor cells, which was significantly higher than common sensitive (19del and L858R) or negative EGFR mutation (49.0% vs 12.1% vs 26.3%, respectively, P < 0.05). Furthermore, positive PD-L1 expression was associated with a significantly shortened OS when compared with the negative PD-L1 expression (20.0 vs 44.3 months, P = 0.006). And PD-L1 positivity was predominantly observed among patients with high CD8 expression rather than low cases (72.0% vs 25.0%, P = 0.001). Notably, we found PD-L1 and CD8 dual-positive cases demonstrated the worst prognosis (OS: 19.3[dual-positive] vs 31.1[single-positive] vs 44.3[dual-negative] months, P = 0.023). Additionally, this approach revealed PD-L1 and CD8 positivity were not associated with the response to EGFR-TKIs, playing no role in the de novo resistance of EGFR-TKIs among the uncommon mutated patients. Finally, one patient harboring EGFR G719A mutation with PD-L1 and CD8 dual positivity experienced a favorable response to anti-PD-1 therapy.
Conclusions
This study revealed the expression of PD-L1, CD4 and CD8 in uncommon EGFR-mutated NSCLC patients. The findings indicated the reshaping of an inflamed immune phenotype characterized by PD-L1 and CD8 dual positivity and suggest potential therapeutic sensitivity to PD-1 blockade.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2108 - Biomarker analyses of ramucirumab in patients with platinum refractory urothelial cancer from RANGE, a global, randomized, double-blind, phase 3 study.
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3090 - Comparison of Immuno-Oncology (IO) Biomarkers in Adenocarcinoma (ACB), Urothelial Carcinoma (UCB) and Squamous Cell Carcinoma (SCCB) of the Bladder, with interim results from PURE01
Presenter: Daniele Raggi
Session: Poster Display session 3
Resources:
Abstract
5211 - Potential role of a clinical, taxonomical classification and RNA expression integrated signature to predict response to neoadjuvant platinum-based chemotherapy in muscle-invasive bladder cancer (MIBC) patients
Presenter: Albert Font
Session: Poster Display session 3
Resources:
Abstract
3206 - Hyperphosphatemia due to Erdafitinib (a Pan-FGFR Inhibitor) and Anti-tumor Activity Among Patients (Pts) with Advanced Urothelial Carcinoma (UC)
Presenter: Scott Tagawa
Session: Poster Display session 3
Resources:
Abstract
3110 - Prognostic role of FGFR Mutations and FGFR mRNA expression in metastatic urothelial cancer treated with anti-PD(L1) inhibitors in first and second line setting
Presenter: Florian Roghmann
Session: Poster Display session 3
Resources:
Abstract
3564 - Circulating tumour DNA (ctDNA) utility as a biomarker for metastatic urothelial carcinoma (mUC)
Presenter: Jean-Michel Lavoie
Session: Poster Display session 3
Resources:
Abstract
2760 - Comparative analysis of tumor mutational burden (TMB) prediction methods and its association with determinants of the tumor immune microenvironment of urothelial bladder cancer (UBC)
Presenter: Markus Eckstein
Session: Poster Display session 3
Resources:
Abstract
2513 - The Immunoscore in patients with urothelial carcinoma treated with neoadjuvant chemotherapy: clinical significance for pathological response and survival
Presenter: Elise Nassif
Session: Poster Display session 3
Resources:
Abstract
2835 - Genomic analysis of urothelial cancer and associations with treatment choice and outcome
Presenter: David Sarid
Session: Poster Display session 3
Resources:
Abstract
5763 - cfDNA is an acceptable but insufficient means of characterizing FGFR3 mutation in patients with metastatic urothelial cancer (mUC)
Presenter: Sumanta Pal
Session: Poster Display session 3
Resources:
Abstract