Biomedical Engineering Reference
In-Depth Information
survival for patients with advanced, incurable NSCLC. Trials have
demonstrated that the combination of EGFR inhibitors and cytotoxic
chemotherapy in patients with advanced, incurable disease have
shown no survival benefit over cytotoxic chemotherapy alone in
the first-line setting.
13,14,15,16
Trials assessing these agents in the
adjuvant setting (RADIANT) are currently ongoing and have not yet
reported.
17
The first phase III clinical trial to demonstrate an overall survival
benefit from an EGFR TKI was NCIC Clinical Trials Group (CTG)
BR21 clinical trial.
18
This trial evaluated erlotinib versus placebo
in patients with NSCLC after one or two lines of chemotherapy for
advanced disease. Patients randomized to the erlotinib arm had a
superior overall survival (OS) and quality of life benefit, compared
with patients on the placebo arm (median OS 6.7 months vs. 4.7
months; HR = 0.70,
= <0.001). The Iressa NSCLC Trial Evaluating
REsponse and Survival versus Taxotere (INTEREST) was a phase III
clinical trial with a non-inferiority design that evaluated gefitinib
versus standard second-line cytotoxic chemotherapy docetaxel. The
trial met its non-inferiority endpoint.
p
19
The Iressa Pan-Asian Study
(IPASS) was a second non-inferiority trial in the first-line metastatic
setting, evaluated gefitinib and standard first-line chemotherapy
with carboplatin and paclitaxel in patients of Asian descent, with
adenocarcinoma histology and never smoking/former light smoker
status. This design was based on the observation that the patients
with these clinical features appeared to respond better to EGFR
TKIs.
13,14,15,16
The trial met its non-inferiority endpoint, and has
become a pivotal trial for the validation of the EGFR activating
mutations as a predictive biomarker.
20
Two phase III trials have assessed cetuximab in combination with
platinum-doublets. The FLEX (first-line Erbitux) trial compared the
addition of cetuximab with cisplatin and vinorelbine in the first-line
setting for patients with advanced NSCLC. The addition of cetuximab
resulted in a statistically significant 1.1 month overall survival
benefit and a superior response rate (36% vs. 29%).
21
The BMS-
099 trial assessed whether cetuximab was beneficial in combination
with carboplatin and a taxane. The primary endpoint of the trial was
progression-free survival (PFS). No statistically significant benefit in
terms of the primary endpoint was detected with the trial. There was
a 1.3 month benefit on OS detected, although this was not statistically
significant.
22
