Hong Kong Med J 2014;20:176–7 | Number 3, June 2014
DOI: 10.12809/hkmj144267
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
EDITORIAL
Comparison is beyond IPASS and OPTIMAL
KC Lam, FHKAM (Medicine)1; Tony
SK Mok, FHKCP, FHKAM (Medicine)2
1 Department of Clinical
Oncology, Prince of Wales Hospital, Shatin, Hong Kong
2 Department of Clinical
Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong
Corresponding author: Dr KC Lam (kc_lam@clo.cuhk.edu.hk)
Now that first-line epidermal growth factor
receptor tyrosine kinase inhibitor (EGFR TKI) is recognised as a
standard therapy for non–small-cell lung cancer (NSCLC) with
activating mutations,1 2 3
4 5 6 7 it is only natural for some of us to ask which
TKI is the best. In the absence of a direct head-to-head
randomised controlled study, Lee et al8
used an indirect comparison method to compare the efficacy and
cost-effectiveness of gefitinib and erlotinib, results of which
are published in this issue. The authors concluded that erlotinib
has better efficacy and is more cost-effective than gefitinib.8 Is this a trustworthy conclusion?
For reason that is not entirely clear to
us, authors chose to use data from only the OPTIMAL and IPASS
studies. Truth is that there are four randomised studies on
gefitinib (IPASS, FIRST-SIGNAL, NEJ-002, and WJTOG 345) and three
randomised studies on erlotinib (OPTIMAL, EURTAC, and ENSURE) in
patients with activating EGFR mutation–positive NSCLC. The authors
excluded EURTAC study from the comparison because of the
differences in baseline demographic data and ethnicity. Similar to
IPASS, EURTAC is a registration study using stringent criteria for
documentation of treatment outcomes and toxicity. The OPTIMAL
study was not considered a registration study by the China Food
and Drug Administration, and that was exactly the reason for the
replication of OPTIMAL study (ENSURE study) in China. Grade 3 or
above skin rash rate was higher in the EURTAC study (13%) as
compared with IPASS study (3.1%), and this is a fact that should
not be ignored. The median progression-free survival (PFS) and
hazard ratio were comparable between EURTAC and IPASS and, again,
this fact was ignored. Lee et al8
should incorporate data from more relevant clinical trials into
the indirect comparison to provide a non-biased estimate of the
true treatment effect. As erlotinib is slightly more expensive
than gefitinib in the Hong Kong public health care system, it will
be unrealistic to conclude a better cost-effectiveness if the two
drugs were shown to have similar efficacy in an honest manner.
Kim et al9
conducted a prospective open-label randomised non-comparative
parallel study in a single Korean hospital to evaluate the
efficacy of erlotinib and gefitinib in those EGFR
mutation–positive NSCLC patients or patients with at least two out
of three clinical factors associated with higher incidence of EGFR
mutations who failed platinum-based chemotherapy. In this
exploratory comparison, there were no statistically significant
differences in response rate and median PFS between the two drugs.
More treatment-related grade-3 or -4 adverse events were observed
with erlotinib versus gefitinib (12.4% vs 4.2%). Wu et al10 conducted a retrospective study to evaluate
the difference in efficacy between erlotinib and gefitinib in
Taiwanese patients with advanced-stage EGFR mutation–positive
NSCLC. They also found no statistically significant difference in
response rate and PFS between the two drugs. Lim et al11 performed
a retrospective review to examine the treatment outcomes with two
EGFR TKIs with a match-pair case-control study design. Again,
there were no statistically significant differences in response
rates, PFS, and overall survival between the two drugs. An ongoing
prospective randomised trial in China compares erlotinib with
gefitinib in NSCLC patients harbouring EGFR exon 21 mutation. This
will be the only true head-to-head comparison between gefitinib
and erlotinib in this setting.
While we argue about which is a better EGFR
TKI, treatment paradigm is shifting to second and third
generations of EGFR TKIs. Afatinib, an irreversible pan-HER
inhibitor, has been proven to be superior to standard
platinum-based chemotherapy.12
LUX–Lung 7 trial, a randomised phase IIb study comparing afatinib
to gefitinib in EGFR mutation–positive NSCLC, is completed and
results are pending. Furthermore, ARCHER 1050 will be the first
randomised phase III study comparing dacomitinib with gefitinib in
patients with either exon 19 or 21 mutations. Phase I studies on
third-generation EGFR TKIs including AZ9291 and CO1686 have also
reported high tumour response rate in patients with resistant
T790M mutation. Its role as first-line EGFR TKI remains to be
explored.
Treatment of advanced-stage lung cancer is
rapidly evolving. Instead of asking the question of which is a
better EGFR TKI, perhaps we should focus on how to improve
outcomes for our future patients.
References
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