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Tesi etd-06252014-224356


Thesis type
Tesi di specializzazione (5 anni)
Author
MINUTI, GABRIELE
URN
etd-06252014-224356
Title
PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients
Struttura
RICERCA TRASLAZIONALE E DELLE NUOVE TECNOLOGIE IN MEDICINA E CHIRURGIA
Corso di studi
ONCOLOGIA MEDICA
Commissione
relatore Prof. Falcone, Alfredo
Parole chiave
  • PD-L1
  • PD-1
  • non-small-cell lung cancer
  • tyrosine kinase inhibitors
Data inizio appello
22/07/2014;
Consultabilità
completa
Riassunto analitico
Background: Agents targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) are showing promising results in non-small-cell lung cancer (NSCLC). It is unknown whether PD-1/PD-L1 are differently expressed in oncogene-addicted NSCLC.<br>Methods: We analyzed a cohort of 125 NSCLC patients, including 56 EGFR mutated, 29 KRAS mutated, 10 ALK translocated and 30 EGFR/KRAS/ALK wild-type. PD-L1 and PD-1 expression were assessed by immunohistochemistry (IHC). All cases with moderate or strong staining (2+/3+) in &gt;5% of cells were considered as positive.<br>Results: PD-1 positive (+) was significantly associated with current smoking status (p=0.02) and with presence of KRAS mutations (P=0.006), while PD-L1+ was significantly associated to adenocarcinoma histology (P=0.005) and with presence of EGFR mutations (P=0.001). In patients treated with EGFR tyrosine kinase inhibitors (N=95), sensitivity to gefitinib or erlotinib was higher in PD-L1+ versus PD-L1 negative in terms of response rate (RR: P=0.01) time to progression (TTP: P&lt;0.0001) and survival (OS: P=0.09), with no difference in PD1+ versus PD-1 negative. In the subset of 54 EGFR mutated patients, TTP was significantly longer in PD-L1+ than in PD-L1 negative (P=0.01). <br>Conclusion: PD-1 and PD-L1 are differentially expressed in oncogene-addicted NSCLC supporting further investigation of specific checkpoint inhibitors in combination with targeted therapies.<br>
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