AZ/Merck & Co wow ASCO with pancreatic cancer data

Finding targeted therapies for pancreatic cancer has long been an issue for pharma, meaning that for decades the only real option has been a course of chemotherapy, with unpleasant side-effects and limited efficacy. In most cases the prognosis even with chemotherapy is between eight and 12 months, a “dismal” situation according to Hedy Kindler, from Professor of Medicine at the University of Chicago. Kindler was presenting data from the POLO study that is already being described as a game-changer for a small group of patients with the disease. For between 4% and 7% of patients who have an inherited BRCA1 and/or BRCA2 mutation, AstraZeneca and Merck & Co’s Lynparza (olaparib) could stay progression, and possibly even cause tumours to shrink completely in a small number of cases according to the POLO data. Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor, and has already produced data at ASCO this year in prostate cancer, following in the footsteps of Clovis Oncology’s rival, Rubraca (rucaparib). Findings of POLO showed that in pancreatic cancer patients with the germline BRCA gene, progression-free survival was 7.4 months with Lynparza, compared with 3.8 months in those receiving placebo. The top line is that progression-free survival was 7.4 months compared with placebo, a 47% reduction in risk of progression or death. Duration of response was 24.9 months, compared with 3.9 months on placebo. After two years 22.1% of patients on Lynparza had no disease progression, compared with 9.6% for those treated with placebo. Duration of response was 24.9 months, compared with 3.9 months on placebo. There were two complete responses, ongoing at data cut off. Perhaps the biggest “wow” moment from a presentation at ASCO is the lack of overall survival data after two years. So many patients are still alive in the treatment arm that OS data is not yet available, in this set of data described by a visibly emotional Kindler as “remarkable” in a press briefing. Kindler said: “For patients with BRCA-driven metastatic pancreatic cancer, we may be seeing a change in patients’ disease trajectory.” Findings were based on 247 people screened for BRCA mutations from a sample of 3,315 people with pancreatic cancer. In the study 92 people were randomly assigned to receive Lynparza, and 62 were assigned to placebo. Serious side effects occurred in 40% of people taking Lynparza, compared with 20% in the placebo group, with 5.5% stopping Lynparza treatment compared with 1.7% on placebo. ASCO’s experts noted that because these are inherited mutations, rather than somatic mutations that spring up as the disease progresses, it is easy to sequence a patient’s DNA to find out whether they are eligible to receive Lynparza. There is also the possibility in the future that the drug could be used in BRCA-like somatic mutations in the future, according to ASCO’s experts. José Baselga, AZ’s oncology R&D chief, said: “These unprecedented results raise new hope for patients that have seen little progress over a long period of time. We are now working with regulatory authorities to bring Lynparza to patients as quickly as possible.”