Pneumologie 2012; 66 - P93
DOI: 10.1055/s-0032-1302878

A randomized phase 2 study of pemetrexed vs. pemetrexed+erlotinib in second-line treatment for locally advanced or metastatic, non-squamous NSCLC

J von Pawel 1, Z Papai-Szekely 2, N Vinolas 3, C Sederholm 3, M Klima 4, D Desaiah 5, M Leschinger 6, C Dittrich 7
  • 1Asklepiosfachkliniken München Gauting
  • 2Fejer Megyei Szent Gyorgy Korh, Szekesfehervar, Hungary
  • 3University Hospital, Linköping, Sweden
  • 4Eli Lilly GmbH, Vienna, Austria
  • 5Eli Lilly, Indianapolis, USA
  • 6Lilly Deutschland GmbH
  • 7LBI-ACR VIEnna and ACR-ITR VIEnna, Kaiser Franz Josef-Spital, Vienna

Background: PEM and ERL have been approved as second-line monotherapy for locally advanced or metastatic NSCLC. The combination of PEM + ERL showed synergistic activity in preclinical studies. This multicenter, randomized, open-label study assessed the efficacy and safety of PEM + ERL vs. PEM.

Methods: Patients (pts) with NSQ NSCLC who have failed one prior platinum-based chemotherapy regimen for advanced or metastatic disease, ≥1 measurable lesion by RECIST, and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2 were eligible. Pts received PEM 500mg/m2 (with vitamin B12 and folic acid supplementation) q3w alone or combined with ERL 150mg daily until progression. The primary endpoint of progression-free survival (PFS) was analyzed using the log-rank test with one-sided alpha of 0.20.

Results: Of 165 pts with NSQ NSCLC who were randomized (PEM: 86; PEM + ERL: 79), 159 were treated (PEM: 83 and PEM + ERL: 76). The baseline characteristics for PEM/PEM + ERL were: median age of 61/64yrs, stage IV disease in 84.3%/84.2%, and ECOG PS 2 in 13.3%/12.0% of pts. The median PFS (months) was 2.9 [95% CI: 1.9, 3.4] in PEM versus 3.2 [95% CI: 2.9, 4.7] in PEM + ERL (hazard ratio [HR] 0.63; 95% CI: 0.44, 0.90; log-rank P=0.005). The median overall survival (OS; months) was 7.8 [95% CI: 5.3, 10.4] in PEM versus 11.8 [95% CI: 8.2, 16.7] in PEM + ERL (HR 0.68; 95% CI: 0.47, 0.98; log-rank P=0.019). Response rates were 10.8% in PEM and 17.1% in PEM + ERL; disease-control rates were 51.8% in PEM and 55.3% in PEM + ERL. Two pts died in PEM + ERL due to drug-related lung abscess and febrile neutropenia. Study drug-related grade (G) 3 + 4 laboratory toxicities (in ≥10% of pts) in PEM/PEM + ERL were anemia (6%/11.8%), leukopenia (9.6%/23.7%), neutropenia (9.6%/25.0%), and thrombocytopenia (4.8%/14.5%). G 3 + 4 non-laboratory drug-related toxicities (in ≥5% of pts) in PEM/PEM + ERL were rash (1.2%/9.2%), diarrhea (1.2%/5.3%), and febrile neutropenia (2.4%/10.5%).

Conclusions: PEM + ERL significantly improved PFS and OS compared with PEM, and was well tolerated. The benefit of this combination therapy should be confirmed in a phase III study.