Abstract 4154
Background
Non-small cell lung cancer (NSCLC) patients carrying epidermal growth factor receptor (EGFR) mutations are sensitive to tyrosine kinase inhibitors (TKIs); nonetheless, about 20% of patients show primary resistance to TKIs. We previously demonstrated the association between TP53 mutations and primary resistance to first-line TKIs in EGFR-mutated adenocarcinoma (ADC) patients. Here we analyze a validation case series of ADC patients treated with first-line TKIs to confirm our previous data, and we assess the association between TP53 status and the prognosis of ADC patients treated with third generation TKIs.
Methods
We considered 136 ADC EGFR-mutated patients treated with a TKI in the first-line setting. Also, we analyzed 42 patients who developed T790M mutation and were treated with a third generation TKI in second- or further line setting. EGFR and TP53 mutation analyses were performed by Sanger Sequencing or Next Generation Sequencing methodologies. TP53 mutations were evaluated in relation to disease control rate (DCR: complete response [CR], partial response [PR] or stable disease [SD]), objective response rate (ORR: CR, PR), progression-free survival (PFS) and overall survival (OS).
Results
Of 136 patients, we found 42 (31%) TP53 mutations: 12 mutations in exon 5 (28.6%), 6 in exon 6 (14.3%), 13 in exon 7 (30.9%), and 11 in exon 8 (26.2%). DCR and ORR were 31.8% and 32.5% in TP3-mutated patients with respect to 68.6% and 67.4% in TP53 wild-type (wt) patients, respectively. Exon 8 TP53-mutated patients had a worse PFS with respect to TP53 wt patients (HR 3.19 [1.62-6.27], p = 0.001), but not OS. Moreover, we assessed TP53 status in 42 patients who developed a T790M mutation and received a third generation TKI in second or additional lines of treatment. In 30 patients with evaluable clinical response, DCR and ORR were 62.5% and 25% in TP53 mutated patients, with respect to 77.2% and 54.5% in the TP53 wt patients, respectively. Data analyses of PFS and OS are ongoing.
Conclusions
EGFR-mutated NSCLC patients with concomitant TP53 mutations had a worse clinical response to first-, second-, and third generation TKIs, administrated in any line of treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5939 - Matrix metalloproteinases and their tissue inhibitors genes abnormal DNA methylation in breast cancer
Presenter: Olga Simonova
Session: Poster Display session 1
Resources:
Abstract
2703 - Uveal melanoma cell lines depend on multiple signaling pathways for survival
Presenter: John Park
Session: Poster Display session 1
Resources:
Abstract
4849 - XAF1 and ZNF313 complex stimulates ER stress-induced apoptosis via direct GRP78 inhibition.
Presenter: Sungchan Jang
Session: Poster Display session 1
Resources:
Abstract
4801 - XAF1 assembles a destructive complex to induce BRCA1-mediated apoptosis via suppressing ERa and switching estrogen function
Presenter: Seung-hun Jang
Session: Poster Display session 1
Resources:
Abstract
3416 - Cancer associated fibroblasts promote cancer progression via Wnt2 secretion in colorectal cancer
Presenter: Hideaki Karasawa
Session: Poster Display session 1
Resources:
Abstract
4273 - Paired-related homeobox 1 overexpression promotes invasion and metastasis and is a prognostic factor for worse disease-free survival in patients with lung cancer
Presenter: Jung-jyh Hung
Session: Poster Display session 1
Resources:
Abstract
4241 - LncRNA-GC1 contributes to gastric cancer chemo-resistance through inhibition of miR-551b-3p and the overexpression of dysbindin
Presenter: Xin Guo
Session: Poster Display session 1
Resources:
Abstract
5388 - GLPG 1790, a new selective EPHA2 inhibitor, is active in colorectal cancer cell lines belonging to the CMS4/mesenchymal-like subtype
Presenter: Pietro Paolo Vitiello
Session: Poster Display session 1
Resources:
Abstract
5208 - Characterisation of growth hormone signal transduction in primary melanoma cell lines
Presenter: Karla Sousa
Session: Poster Display session 1
Resources:
Abstract
3156 - LAPTM5 protein can regulate TGF-β mediated MAPK and Smad signaling pathways in ovarian cancer cell
Presenter: Yan Gao
Session: Poster Display session 1
Resources:
Abstract