“THE RATIONALE for the POLO study is sound,” said invited study discussant Wells Messersmith, MD. “There’s clearly an unmet need in pancreatic cancer, and there are promising data for poly (ADP-ribose) polymerase (PARP) inhibitors in other BRCA-mutated tumors.” Dr. Messersmith is Professor and Head of Medical Oncology, Associate Director for Translational Research, at the University of Colorado Cancer Center.
Wells Messersmith, MD
Allyson Ocean, MD
Allyson Ocean, MD, a medical oncologist and Associate Professor of Clinical Medicine at NewYork-Presbyterian and Weill Cornell Medicine, New York, called the data “practice-changing” and applauded the POLO investigators “for leading the effort to improve outcomes in this patient population. The combined strategy of initial platinum-based chemotherapy followed by maintenance olaparib resulted in a significant progression-free survival benefit, even after 2 years on study. There was no overall survival benefit noted; however, the overall survival data were only 46% mature. I think there’s more to come. Now we need to think of other trials with olaparib including combination with chemotherapy and also immunotherapy.”
Daunting Task, Big Payoff
EXPLORING THE use of olaparib in pancreatic cancer was daunting, Dr. Messersmith noted. “Of 3,315 patients screened, just 154 were enrolled, or 4.6%. Thus, finding these patients was challenging, and the investigators are to be commended…. They have also accomplished a first in pancreatic cancer: a successful biomarker-driven trial with germline mutations, and a successful maintenance design.”
According to Dr. Messersmith, the payoff was big: “Though the improvement in progression-free survival was incremental, the effect size of 3.5 months and the hazard ratio of 0.53 are considerable in the context of patients with pancreatic cancer.”
FOR DR. MESSERSMITH, the main message is the need for widespread testing for BRCA and other hereditary mutations. He noted that this message has been echoed recently by the National Comprehensive Cancer Network®. Regarding treatment outcomes, maintenance olaparib is now “an option” for patients with germline BRCA mutations, according to Dr. Messersmith. “However, it is reasonable also to continue platinum-based chemotherapy.”
Dr. Ocean agreed with Dr. Messersmith on the key message of POLO: “All patients with pancreatic cancer should undergo germline genetic testing to uncover those who will benefit most from using olaparib in their treatment plan.”
“We also must encourage patients and family members who harbor germline BRCA mutations to enter screening clinical trials,” she continued. “I have seen numerous patients with metastatic BRCA-mutated pancreatic cancer who were known gene carriers prior to being diagnosed or who knew that the gene existed in their family and were not screened. I encourage all patients and their family members who carry the BRCA gene or another gene that predisposes to pancreatic cancer to seek out a screening study such as the Generate Study, which is supported by Stand Up To Cancer and The Lustgarten Foundation,” Dr. Ocean said. ■
DISCLOSURE: Dr. Messersmith has served as a consultant or advisor in an institutional capacity for Five Prime Therapeutics, Gilead Sciences, and Tanabe Research and has received institutional research funding from Pfizer, Roche/Genentech, OncoMed, Immunomedics, Alexo Therapeutics, Takeda, Aduro Biotech, AstraZeneca, D3 Pharma, and BeiGene. Dr. Ocean has served on the advisory board for Celgene, Daiichi Sankyo, Tyme, and Array BioPharma.
In patients with metastatic pancreatic cancer and germline mutations in BRCA1 or BRCA2, maintenance therapy with olaparib doubled the time to disease progression and the proportion of patients who were progression-free at 2 years, in the phase III POLO trial.1
Hedy Lee Kindler, MD