Phase II study of pemetrexed and cisplatin plus cetuximab followed by
pemetrexed and cetuximab maintenance therapy in patients with advanced
nonsquamous non-small cell lung cancer
Objectives: The aim was to determine if combined pemetrexed, cisplatin,
and cetuximab was efficacious and safe as first-line treatment in
advanced nonsquamous non-small cell lung cancer (NSCLC).
Patients and methods: In this single-arm, multicenter clinical trial,
patients with Stage IIIB/IV nonsquamous NSCLC received first-line
therapy consisting of pemetrexed (500 mg/m(2)) and cisplatin (75 mg/m2)
on Day 1 (21-day cycles) plus weekly cetuximab (400 mg/m(2) loading
dose, then 250 mg/m(2)) for 4-6 cycles. Non-progressing patients
received maintenance therapy consisting of pemetrexed and cetuximab as
above until disease progression. All patients received vitamin
supplementation, dexamethasone, and antihistamine prophylaxis. The
primary endpoint was objective response rate (ORR). Secondary endpoints
were progression-free survival (PFS), 1-year survival rate,
translational research (TR) and safety.
Results: Of the 113 patients receiving study drug, 109 were
protocol-qualified. All patients completed >= 1 cycle of induction, and
51 (45%) and 49 (43%) patients completed >= 1 cycle of maintenance
with pemetrexed and cetuximab, respectively. The ORR (n=109) was 38.5%
(80% confidence interval [CI], 32.3-45.1%), all partial responses.
Median PFS was 5.8 (80% CI, 4.4-6.7) months. One-year survival rate was
45% (80% CI, 39-51%). In exploratory analyses, there was some
preliminary evidence of potential prognostic relationships with efficacy
outcomes for epidermal growth factor receptor and thyroid transcription
factor-1 protein expression, but not for KRAS mutation or for
thymidylate synthase or folate receptor-alpha protein expression.
Seventy-three (64.6%) patients had study drug-related Grade 3/4 adverse
events (AEs). Drug-related serious AEs were reported in 31 (27.4%)
patients. There were 3 (2.7%) potentially drug-related deaths on-study
or within 30 days of follow up.
Conclusion: Pemetrexed, cisplatin, and cetuximab appeared efficacious
and tolerable in advanced nonsquamous NSCLC patients. The TR outcomes
are hypothesis-generating given the study’s size and nonrandomized
nature. (C) 2013 Elsevier Ireland Ltd. All rights reserved
