(Tarceva) alone demonstrated
significant activity as first-line chemotherapy
against advanced nonsmall-
cell lung cancer (NSCLC) in a
phase II trial conducted in The Netherlands,
France, and Switzerland. The
findings showed that the tyrosine kinase
(TK) inhibitor had efficacy similar
to that observed with the most
active cytotoxic agents, said coinvestigator
Jean-Charles Soria, MD, PhD,
of the division of cancer medicine,
Institute Gustave Roussy, Villejuif,
France (abstract 7073).
The trial enrolled 54 patients with
stage IIIb or IV NSCLC who had not
had previous chemotherapy. Participants
received 150 mg of erlotinib per
day until disease progression or unacceptable
At 6 weeks, 55% of patients had
either a complete response, partial response,
or stable disease. Among the
23% with complete or partial responses,
the median duration of response
was 256 days (Table 1).
The majority of the responses occurred
in women, never smokers, and
patients with adenocarcinoma and/or
bronchioalveolar carcinoma, Dr. Soria
said. However, responses were also
observed in men, current smokers, andpatients with squamous cell carcinoma.
The one complete response occurred
in a male current/former smoker
Tissue samples were available for
only five of the responders, and just
one of those had the epidermal growth
factor receptor (EGFR) mutations associated
with response to TK inhibi-tors. Mutations in the K-ras gene were
found only in patients who did not
respond to erlotinib, Dr. Soria said.
Overall, adverse effects were mild.
Diarrhea and rash were most common,
including grade 3 rash in three
patients and grade 3 diarrhea in two
patients. There were no grade 4 toxicities.
Three patients discontinued
treatment because of side effects and
five had their dose reduced to 100 mg.
This is one of the first studies of
erlotinib as first-line therapy in a generalpopulation of NSCLC patients,
said Roman Perez-Soler, MD, chief of
the oncology division in the department
of medicine at Montefiore Medical
Center, New York. As the discussant
of this trial and of other
investigations of TK inhibitors, he
noted that the only other trial of firstline
erlotinib was in elderly patients.
"Despite the favorable demographics,
I think the response rate appears
higher than that observed in secondline
studies," Dr. Perez-Soler said. The
implication of the findings, he said, is
that as a single agent, erlotinib may be
as active as the classical chemotherapy
agents and could now be tested as
first-line therapy in a phase III trial
comparing it with standard chemotherapy
in selected patients.