Gefitinib (IRESSA) versus docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer pre-treated with platinum-based chemotherapy: a randomized, open-label Phase III study (INTEREST): PRS-02

Background:

This Phase III, randomized, open-label, multicenter, parallel-group study (INTEREST [IRESSA non-small-cell lung cancer (NSCLC) Trial Evaluating REsponse and Survival against Taxotere]), compared gefitinib with docetaxel in patients with locally advanced or metastatic NSCLC pretreated with platinum-based chemotherapy. This is the largest reported Phase III study comparing targeted therapy (gefitinib) with chemotherapy (docetaxel).

Methods:

Patients (≈18 years, performance status [PS] 0-2) with locally advanced or metastatic NSCLC who had progressed or recurred following 1 or 2 prior chemotherapy regimens (at least 1 platinum-based) were randomized to receive gefitinib (250 mg/day orally) or docetaxel (75 mg/m² iv every 3 weeks). The primary objective was to compare overall survival between gefitinib and docetaxel using a co-primary analysis in both the overall population (non-inferiority) and, as a protocol amendment following the emergence of biomarker data, in patients with high epidermal growth factor receptor (EGFR) gene copy number (measured by fluorescence in situ hybridization) (superiority). Secondary endpoints were progression free survival, objective response rate (assessed by RECIST), patient-reported functionality and quality of life (measured using the Functional Assessment of Cancer Therapy-Lung total score, trial outcome index and lung cancer subscale), and safety and tolerability (according to Common Toxicity Criteria version 2.0). Exploratory endpoints including other biomarkers and quality of life endpoints were also assessed. A Cox proportional hazards model analysis adjusting only for randomized treatment was used to compare overall survival between the randomized treatments.

Results:

1466 patients from 149 centers in 24 countries were randomized to gefitinib (n=733) or docetaxel (n=733); 323 patients were of Asian racial origin. In the gefitinib and docetaxel treatment arms, respectively, 54% and 55% had adenocarcinoma, 36% and 33% were female, and 20% and 21% were never-smokers. 30%, 58%, 12% and 25%, 63%, 12% had PS 0, 1, 2 in the gefitinib and docetaxel treatment arms, respectively and 15% and 17%, respectively, had undergone 2 prior chemotherapy regimens. 453 patients provided a tumour sample giving at least one evaluable biomarker. Full results will be presented at the conference.

Conclusions:

In this Phase III study comparing gefitinib with docetaxel in patients with locally advanced or metastatic NSCLC pretreated with platinum-based chemotherapy, the treatment groups were well balanced in terms of patient demographics and baseline characteristics. Full results will be presented at the conference.