Background: In a previous trial, evaluating the correlation between P-AKT status and gefitinib activity, compared to the P-AKT negative group, P-AKT positive patients had a better RR (P=0.003), disease control rate (P<0.001), and significantly longer TTP (P=0.004) (PASCO 2004). In that study however, almost 40% of P-AKT positive patients did not benefit from gefitinib therapy. The hypothesis from preclinical data indicated that loss of PTEN can lead to aberrant AKT activation, and finally to gefitinib resistance. Based on the above data we decided to investigate if the loss of PTEN could be responsible for the lack of gefitinib activity in P-AKT positive patients. Patients and methods: Specimens from patients enrolled in our previous trial were evaluated for PTEN expression by immunohistochemistry. Paraffin-embedded tissue sections were stained with mouse monoclonal anti-PTEN antibodies. Results: Among the 106 NSCLC patients enrolled onto the AKT trial, 99 were evaluable for PTEN status. In the whole population, loss of PTEN was observed in 40.4% of patients. No difference in RR, disease control rate, TTP, and OS was observed between patients with and without loss of PTEN (CR+PR: 7.5% versus 15.2%; CR+PR+SD: 40% versus 37.3%; median TTP: 3.4 versus 2.98 months, P= 0.7; median OS: 8.4 versus 11.4 months, P= 0.41). In the univariate analysis, loss of PTEN was not related to P-AKT status, gender, histology, PS, skin toxicity, and smoking history. Among the 51 P-AKT positive patients, 48 were evaluated for PTEN expression, and 19 had loss of PTEN (39.5%). RR and disease control rate were not different in the group with and without loss of PTEN (CR+PR: 15.7% versus 24.1%; CR+PR+SD: 57.8% versus 51.7%, respectively). No difference between the two groups was observed in TTP (median 5.1 versus 4.2 months) and OS (median 8.9 versus 11.4 months). Conclusions: These results suggest that detection of loss of PTEN is not useful in selecting patients potentially resistant to gefitinib therapy.
Federico Cappuzzo, Elisabetta Magrini, Stefania Bartolini, Vienna Ludovini, Giovanni Ceresoli, Laura Lombardo, et al. (2004). Role of loss of pten in phospho-akt (p-akt) positive patients with advanced non-small cell lung cancer (nsclc) treated with gefitinib. BOLOGNA : sine nomine.
Role of loss of pten in phospho-akt (p-akt) positive patients with advanced non-small cell lung cancer (nsclc) treated with gefitinib
MAGRINI, ELISABETTA;DAMIANI, STEFANIA;
2004
Abstract
Background: In a previous trial, evaluating the correlation between P-AKT status and gefitinib activity, compared to the P-AKT negative group, P-AKT positive patients had a better RR (P=0.003), disease control rate (P<0.001), and significantly longer TTP (P=0.004) (PASCO 2004). In that study however, almost 40% of P-AKT positive patients did not benefit from gefitinib therapy. The hypothesis from preclinical data indicated that loss of PTEN can lead to aberrant AKT activation, and finally to gefitinib resistance. Based on the above data we decided to investigate if the loss of PTEN could be responsible for the lack of gefitinib activity in P-AKT positive patients. Patients and methods: Specimens from patients enrolled in our previous trial were evaluated for PTEN expression by immunohistochemistry. Paraffin-embedded tissue sections were stained with mouse monoclonal anti-PTEN antibodies. Results: Among the 106 NSCLC patients enrolled onto the AKT trial, 99 were evaluable for PTEN status. In the whole population, loss of PTEN was observed in 40.4% of patients. No difference in RR, disease control rate, TTP, and OS was observed between patients with and without loss of PTEN (CR+PR: 7.5% versus 15.2%; CR+PR+SD: 40% versus 37.3%; median TTP: 3.4 versus 2.98 months, P= 0.7; median OS: 8.4 versus 11.4 months, P= 0.41). In the univariate analysis, loss of PTEN was not related to P-AKT status, gender, histology, PS, skin toxicity, and smoking history. Among the 51 P-AKT positive patients, 48 were evaluated for PTEN expression, and 19 had loss of PTEN (39.5%). RR and disease control rate were not different in the group with and without loss of PTEN (CR+PR: 15.7% versus 24.1%; CR+PR+SD: 57.8% versus 51.7%, respectively). No difference between the two groups was observed in TTP (median 5.1 versus 4.2 months) and OS (median 8.9 versus 11.4 months). Conclusions: These results suggest that detection of loss of PTEN is not useful in selecting patients potentially resistant to gefitinib therapy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
