Source: Eur J Ophthalmol  |  Posted 6 years ago

By Chris Berrie

BARCELONA, SPAIN -- July 6, 2005 -- The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib (Iressa) demonstrates a similar efficacy to docetaxel that is accompanied by a more favorable tolerability profile as second-line monotherapy in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC), according to an international, multicenter, randomized, parallel-group, open-label, phase 2 study (E4599).

Eduard Vrdoljak, MD, PhD, principal investigator and chief, division of oncology and radiotherapy, Center of Oncology, Clinical Hospital of Split, Split, Croatia, presented the results here on behalf of the Second-line Indication of Gefitinib in NSCLC (SIGN) Investigators on July 4[^]th[] at the 11[^]th[] World Conference on Lung Cancer (WCLC).

"Second-line treatment of metastatic or advanced non-small-cell lung cancer is rather problematic, and right now the only registered treatment is with docetaxel and pemetrexed, both of which are cytostatic, and are accompanied by a lot of side effects," said Dr Vrdoljak.

As these are also the patients that are less able to take such toxic treatments, the search continues for alternative treatment options following relapse on initial chemotherapy, he said.

This phase 2 trial was the first to compare gefitinib against docetaxel as second-line monotherapy for patients with advanced NSCLC who had failed one prior chemotherapy regimen.

Following the randomization of 68 patients to gefitinib (median age, 63.0; range, 34-85 years; male, 69%) and 73 to docetaxel (median age, 59.5 years; range, 29-83; male, 70%), baseline demographics were similar for performance status, metastatic disease, prior cancer treatment, and ever-smoked status.

Patients received 250 mg/day oral gefitinib continuously or 75 mg/m[^]2[] docetaxel on day 1 every 3 weeks until disease progression, unacceptable toxicity or withdrawal of consent. The mean number of 21-day gefitinib treatment periods was 5.3, and for the docetaxel 21-day treatment cycles, 4.3.

The primary endpoint was symptom improvement as assessed at baseline and after every 3 weeks using the Lung Cancer Subscale (LCS) of the Functional Assessment of Cancer Therapy - Lung (FACT-L) questionnaire.

The secondary endpoints were quality of life (complete FACT-L questionnaire), objective response rate, disease control rate, overall survival, and safety.

Patients in the study were symptomatic, with baseline LCS scores of 16.8 and 17.2 for the gefitinib and docetaxel, respectively. Similarly, the patients had a compromised quality of life at baseline, with mean FACT-L scores of 83.8 and 86.2, respectively.

Similar symptom improvement and quality-of-life outcomes were seen for gefitinib versus docetaxel: 36.8% versus 26.0% and 33.8% versus 26.0%, respectively. For those showing improvement, the mean times to improvement were 22 versus 27 days for gefitinib and docetaxel, respectively.

Objective response rates were 13.2% versus 13.7% (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.47- 2.03), with disease control experienced by 63.2% versus 58.9%, respectively (OR, 1.19; 95% CI, 0.61-2.33). Median time to response was 23.0 (range, 22-72) versus 41.5 (range, 23-110) days, respectively.

At a median follow-up of 9.2 months for gefitinib and 9.4 months for docetaxel, no difference in survival outcomes were seen for gefitinib versus docetaxel, with median overall survivals of 7.5 and 7.1 months (hazard ratio [HR], 0.97; 95% CI, 0.61-1.52; P =.88); median progression-free survivals of 3.0 versus 3.4 months (HR, 0.94; 95% CI, 0.64-1.39; P =.76).

Gefitinib achieved a greatly reduced rate of grade 3/4 neutropenia (1.6% vs 46.0%) and leukopenia (0.0% vs 37.3%), although there were no further large differences for the other hematological parameters tested of anemia (4.5% vs 1.5%), thrombocytopenia (1.5% vs. 0.0%), and febrile neutropenia (0.0% vs 3.2%).

Nonhematological adverse events were similar across the 2 treatment arms, although overall, gefitinib was better tolerated than docetaxel, with fewer drug-related adverse events (42% vs 67%) and withdrawals due to toxicity (3% vs 10%).

Dr. Vrdoljak indicated that these results support the further investigation of overall survival for second-line treatment with gefitinib and docetaxel that is now ongoing in the phase 3 Iressa NSCLC Trial Evaluating Response and Survival against Taxotere (INTEREST) study.

[Study title: SIGN: a Phase 2, Open-Label, Randomised Study Comparing Gefitinib (Iressa) With Docetaxel as Second-Line Therapy in Patients With Advanced (Stage IIIB Or IV) Non-Small-Cell Lung Cancer. Abstract PD-070]