Gefitinib + Olaparib

Gefitinib + olaparib is a combination therapy that targets two different cellular mechanisms in cancer cells. Gefitinib inhibits the epidermal growth factor receptor (EGFR) tyrosine kinase, blocking the ATP-binding site of the enzyme and preventing downstream signaling cascades that promote cancer cell survival and proliferation[8]. Olaparib is a PARP inhibitor that prevents the repair of single-strand DNA breaks, which can lead to double-strand breaks and ultimately cell death, particularly in cells with defective DNA repair mechanisms like those with BRCA mutations[4]. The rationale behind this combination was based on research showing that low BRCA1 mRNA levels correlate with longer progression-free survival (PFS) in EGFR-mutant NSCLC patients treated with erlotinib. Since olaparib can reduce BRCA1 expression, it was hypothesized that adding it to gefitinib might improve outcomes in EGFR-mutant advanced NSCLC[1][6]. The combination was evaluated in the GOAL study, a multicenter, randomized phase IB/II trial conducted in Spain and Mexico. The recommended phase 2 dose was determined to be 250 mg of gefitinib once daily plus 200 mg of olaparib three times daily in 28-day cycles[3][6].

Brand names

IressaLynparza

Other names

Gefitinib plus olaparibGefitinib and olaparib