ROCKVILLE, MarylandThe Food and Drug Administration
(FDA) has approved Tarceva tablets
(erlotinib, OSI Pharmaceuticals) as a
single-agent treatment for patients
with locally advanced or metastatic
non-small-cell lung cancer (NSCLC)
whose disease has continued to
progress despite other therapies, including
at least one prior chemotherapy
regimen. The FDA granted marketing
approval on the basis of
increased survival findings in the
Tarceva-treated arm of a phase III trial
in patients who had received second-
or third-line therapy for advanced NSCLC. The primary endpoint
of the study was overall survival.
Secondary endpoints included
progression-free survival and tumor
response rate.
Tarceva, developed by OSI and
distributed by Genentech, is an epidermal
growth factor receptor (EGFR)
inhibitor, and it is the first of the class
to demonstrate a survival advantage
for advanced NSCLC in a phase III
trial. However, two large, randomized
studies of Tarceva given concurrently
with doublet platinum-based
chemotherapy in previously untreated
advanced NSCLC failed to show clinical benefit, and the drug is not
recommended for such use.
The pivotal study involved 731 patients
with locally advanced or metastatic
NSCLC in a randomized,
double-blind, placebo-controlled
trial conducted in 17 countries. Patients
were randomized 2:1 to receive
Tarceva 150 mg or placebo, administered
orally once daily until disease
progression or unacceptable toxicity.
Survival, progression-free survival,
and tumor response all proved significant
in favor of Tarceva (P < .001).
Median survival, evaluated in an intent-to-treat population, was 6.7
months for Tarceva vs 4.7 months for
placebo. Median progression-free survival
was 9.9 vs 7.9 weeks, respectively,
and the Tarceva-treated patients had a tumor response rate of 8.9% vs
0.9% for placebo. One-year survival
was 31.2% in the treatment group vs
21.5% for the control patients, and
median duration of response was 34.3
vs 15.9 weeks, respectively.
EGFR status was not part of the
study protocol, and survival was seen
in a broad range of patients. Survival
among EGFR-positive patients was
looked at retrospectively, however.
Among the 238 patients with a known
EGFR status, the 78 EGFR-positive
Tarceva-treated patients had a better
survival rate than the 49 EGFR-positive
placebo patients. Tarceva did not
appear to affect survival in the EGFRnegative
subgroup (HR = 1.01). A
survival benefit due to Tarceva in the
EGFR-negative subgroup cannot be
excluded, however, because the confidence
intervals for the EGFR-positive,
-negative, and unmeasured
subgroups are wide and overlap (see
Table 1).
The most common adverse reactions
in patients receiving Tarceva
were rash and diarrhea.
