FLEX: A randomized,multicenter, phase III study of cetuximab in combination with cisplatin/ vinorelbine (CV) versus CV alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC)

Carolyn Vachani, RN, MSN, AOCN
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 23, 2008

Epidermal growth factor (EGFR) is over expressed in 80% of lung cancers. Cetuximab is a monoclonal antibody that interferes with EGFR. A previous randomized phase II FLEX (First-Line Treatment for Patients with EGFR-expressing Advanced NSCLC) trial compared cisplatin and vinorelbine (CV) to cisplatin, vinorelbine, and cetuximab (CV+C) in patients with advanced NSCLC. Forty-three patients were randomized to each arm. Improvement in outcomes were seen with the addition of cetuximab; tumor response was improved from 28% to 35% with addition of cetuximab, progression-free survival was improved from 4.6 months to 5 months, and overall survival was improved from 7.3 to 8.3 months (Rosell, 2008).

Data from the FLEX phase II trial prompted the design of the FLEX phase III trial a larger trial utilizing the same therapies as FLEX II in more patients to evaluate survival benefit.

1125 patients participated in the study, with 94% having stage IV disease. Median overall survival* (OS) was 11.3 months in the CV + C arm, versus 10.1 months in the CV arm. One-year OS was 47% and 42% in the CV + C arm versus CV arm, respectively, which was statistically significant. As far as variation in side effects in the two groups, as expected, 10% patients receiving cetuximab developed rash, while virtually no one in the CV arm developed rash. Neutropenic fever was seen in 22% of those receiving CV+C versus 15% in the CV arm.

The authors point out the survival benefit, which is quite small, as reason to change standard therapy, but one must consider the cost of adding cetuximab to all regimens. Patients with adenocarcinoma appeared to derive the most benefit from the addition of cetuximab. Further research may determine a way to better classify which patients will derive the most benefit. In the meantime, this trial demonstrates a modest but real survival advantage for patients with advanced NSCLC treated with cetuximab added to conventional chemotherapy versus chemotherapy alone. This data is interesting and supports findings in head and neck and colorectal cancer that cetuximab is effective and safe when utilized concurrently with conventional chemotherapy. These findings are clinically important, and are an important contribution to the literature regarding treatment of patients with NSCLC.

* The median is the “middle of the pack”, where half of the patients have had more years since treatment and half have had less. For instance, if the patients were 2, 4, 6, 10.8, 12, 12 and 14 years since treatment, 10.8 is the mid point, or the median. It is different from the mean, which would be the average time since treatment.