Results from the POLO trial demonstrate that patients treated with olaparib (Lynparza, AstraZeneca and Merck & Co., Inc.) compared with placebo had statistically significant and clinically meaningful improvement in progression-free survival (median, 7.4 months vs. 3.8 months, respectively). In addition, more than twice the number of patients showed no disease progression at one year (34% on olaparib vs. 15% on placebo) and at two years (22% vs. 10%, respectively).
Pancreatic cancer is the 12th most common cancer worldwide, and has the worst survival rate among the most common cancers. Early diagnosis is difficult as symptoms usually manifest in late stages, and approximately 80% of patients are diagnosed at the metastatic stage. Fewer than 3% of patients with metastatic pancreatic cancer survive more than five years after diagnosis.
Olaparib’s safety and tolerability profile was similar to that observed in prior clinical trials. The most common adverse events were fatigue/asthenia (60%), nausea (45%), abdominal pain (29%), diarrhea (29%), anaemia (28%), decreased appetite (25%) and constipation (23%).
The phase 3 randomized, double-blinded, placebo-controlled, multicenter POLO trial compared olaparib tablets as maintenance monotherapy versus placebo in 154 patients with gBRCAm metastatic pancreatic cancer whose disease had not progressed on first-line platinum-based chemotherapy. Patients were randomized (3:2) to olaparib or placebo until disease progression. The primary endpoint was progression-free survival, and key secondary endpoints included overall survival, time to second disease progression, overall response rate, disease control rate, and health-related quality of life.
Olaparib is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumors harboring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2.
Source: AstraZeneca, June 3, 2019