A randomised phase II study of pemetrexed versus pemetrexed+erlotinib as second-line treatment for locally advanced or metastatic non-squamous non-small cell lung cancer.
BACKGROUND
Pemetrexed and erlotinib have been approved as second-line monotherapy for locally advanced or metastatic non-small cell lung cancer (NSCLC). This multicentre, randomised, open-label, parallel phase II study assessed efficacy and safety of pemetrexed versus pemetrexed+erlotinib in patients with advanced non-squamous NSCLC.


METHODS
NSCLC stage III-IV patients who failed one prior platinum-based chemotherapy regimen, ≥ 1 measurable lesion by Response Evaluation Criteria in Solid Tumors, and Eastern Cooperative Oncology Group performance status ≤ 2 were eligible. Patients received pemetrexed 500 mg/m(2) with vitamin B12 and folic acid q3w alone or combined with erlotinib 150 mg daily. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), time-to-treatment failure (TTTF), response and toxicity.


RESULTS
Of 165 randomised non-squamous patients, 159 were treated (pemetrexed: 83; pemetrexed+erlotinib: 76). The median PFS (months; 95% CI) was 2.89 (1.94, 3.38) for pemetrexed versus 3.19 (2.86, 4.70) for pemetrexed+erlotinib (hazard ratio [HR] 0.63; 95% CI: (0.44, 0.90); P = 0.0047). The median OS (months; 95% CI) was 7.75 (5.29, 10.41) for pemetrexed versus 11.83 (8.18, 16.66) for pemetrexed+erlotinib (HR: 0.68; 95% CI: 0.46, 0.98; P = 0.019). The median TTTF (months: 95% CI) was 2.4 (1.74, 2.99) for pemetrexed versus 3.0 (2.23, 4.07) for pemetrexed+erlotinib (HR 0.64; 95% CI: 0.46, 0.89; P = 0.0034). One patient died in pemetrexed+erlotinib arm due to febrile neutropenia. Grades 3/4 drug-related toxicities (in ≥ 5% of patients) in pemetrexed/pemetrexed+erlotinib were febrile neutropenia (2.4%/10.5%), diarrhoea (1.2%/5.3%), rash (1.2%/9.2%); anaemia (6%/11.8%), leukopenia (9.6%/23.7%), neutropenia (9.6%/25.0%), and thrombocytopenia (4.8%/14.5%).


CONCLUSIONS
Pemetrexed+erlotinib treatment significantly improved PFS, OS and TTTF in 2nd line non-squamous NSCLC and was associated with an increase in grade 3/4 toxicities compared with pemetrexed alone.
LBI-ACR VIEnna and ACR-ITR VIEnna, Kaiser Franz Josef-Spital, Vienna, Austria. Electronic address: christian.dittrich@wienkav.at.
Christian
C
Dittrich
St. George Hospital of Fejér County, Szekesfehervar, Hungary.
Zsolt
Z
Papai-Szekely
Hospital Clinic I Provincial, Barcelona, Spain.
Nuria
N
Vinolas
University Hospital, Linköping, Sweden.
Christer
C
Sederholm
Department of Internal Medicine II-Hematology and Medical Oncology, Kiel, Germany and Catholic Hospital Consortium Ostwestfalen, Bielefeld, Germany.
Joerg T
JT
Hartmann
Clinic of Hematology and Oncology, Bochum, Germany.
Dirk
D
Behringer
Eli Lilly UK, Erl Wood Manor, Windlesham, Surrey, United Kingdom.
Gbenga
G
Kazeem
Eli Lilly Corporate Center, Indianapolis, USA.
Durisala
D
Desaiah
Lilly Deutschland GmbH, Bad Homburg, Germany.
Monika I
MI
Leschinger
Asklepios Hospital München-Gauting, Gauting, Germany.
Joachim
J
von Pawel
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000068437:Pemetrexed; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D005971:Glutamates; D011799:Quinazolines; D000068437:Pemetrexed; D006147:Guanine; D000069347:Erlotinib Hydrochloride
Erlotinib; Non-small cell lung cancer; Non-squamous; Pemetrexed; Second-line therapy