Pemetrexed with or without matuzumab as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer.
BACKGROUND
This randomized phase II study investigated pemetrexed in combination with the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer.


METHODS
Patients received pemetrexed 500 mg/m every 3 weeks either alone (n = 50) or in combination with matuzumab at either 800 mg weekly (n = 51) or 1600 mg every 3 weeks (n = 47). The primary end point was objective response, as assessed by an independent review committee.


RESULTS
Tumor EGFR expression was detected in 87% of randomized patients. The objective response rate for the pooled matuzumab-treated arms was 11% compared with 5% for pemetrexed alone (p = 0.332). Apart from one patient in the pemetrexed alone group, all responses occurred in patients whose tumors expressed EGFR. The objective response rate for patients receiving weekly matuzumab was 16% compared with 2% for those receiving matuzumab every 3 weeks. There was also a trend for improved overall survival in patients receiving matuzumab weekly versus every 3 weeks (12.4 months versus 5.9 months, respectively, versus 7.9 months for pemetrexed alone). The combination of pemetrexed and matuzumab demonstrated an acceptable safety profile, with the most common grade 3/4 adverse event being neutropenia.


CONCLUSIONS
Although the analysis on the pooled matuzumab-treated arms did not demonstrate a statistically significant improvement in objective response for the addition of matuzumab to pemetrexed compared with pemetrexed alone, the trends for improvement in objective response and overall survival for pemetrexed plus weekly matuzumab compared with pemetrexed alone warrant confirmation in additional clinical trials.
Schiller
Joan H
JH
Division of Hematology and Oncology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Texas, USA.
von Pawel
Joachim
J
Schütt
Philipp
P
Ansari
Rafat H
RH
Thomas
Michael
M
Saleh
Mansoor
M
McCroskey
Robert D
RD
Pfeifer
Wolfgang
W
Marsland
Thomas A
TA
Kloecker
Goetz H
GH
Sebastian
Martin
M
Pirker
Robert
R
Kurek
Raffael
R
Beadman
Claire
C
Socinski
Mark A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011788:Quality of Life
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D066246:ErbB Receptors; C520777:matuzumab