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
4021 - Prospective pathological experience with research biopsies in the context of clinical trials at Vall d’Hebron Institute of Oncology
Presenter: Paolo Nuciforo
Session: Poster Display session 3
Resources:
Abstract
5603 - Development of a comprehensive next-generation targeted sequencing assay for detection of gene-fusions in solid tumors
Presenter: Vinay Mittal
Session: Poster Display session 3
Resources:
Abstract
4952 - Next-generation sequencing for better treatment strategy of cancer of unknown primary (CUP)
Presenter: Kang Kook Lee
Session: Poster Display session 3
Resources:
Abstract
4590 - Circulating-free DNA analysis from long-term surviving metastatic colorectal cancer patients undergoing surgery for resectable disease.
Presenter: Michele Ghidini
Session: Poster Display session 3
Resources:
Abstract
3696 - Ultra-sensitive detection of circulating tumor DNA identifies patients in high risk of recurrence in early stages melanoma
Presenter: Filip Janku
Session: Poster Display session 3
Resources:
Abstract
4295 - Identification of the founder BRCA1 mutation c.4117G>T (p.Glu1373*) recurring in Abruzzo and Lazio regions of Central Italy and predisposing to breast/ovarian and BRCA1-related cancers
Presenter: Daniela Di Giacomo
Session: Poster Display session 3
Resources:
Abstract
2214 - Enzalutamide (ENZA) and Apalutamide (APA) In vitro chemical reactivity studies and Activity in a Mouse Drug Allergy Model (MDAM)
Presenter: Mausumee Guha
Session: Poster Display session 3
Resources:
Abstract
5044 - Influence of genetic variation in COMT on cisplatin-induced nephrotoxicity in cancer patients.
Presenter: Bram Agema
Session: Poster Display session 3
Resources:
Abstract
3293 - Cardioprotective and anti-inflammatory effects of Empagliflozin during treatment with Doxorubicin: a cellular and preclinical study
Presenter: Vincenzo Quagliariello
Session: Poster Display session 3
Resources:
Abstract
3324 - Breast Cancer Organoids Model Treatment Response of HER2 Targeted Therapy in HER2-mutant Breast Cancer
Presenter: Xuelu Li
Session: Poster Display session 3
Resources:
Abstract