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Expert Point of View: Efrat Dotan, MD, and Colin D. Weekes, MD, PhD


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Efrat Dotan, MD

Efrat Dotan, MD

Efrat Dotan, MD, Associate Professor, Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, commented on this study. “This abstract presents the interim analysis of a phase II study evaluating the use of maintenance therapy with the poly (ADP-ribose) polymerase PARP inhibitor rucaparib in patients with BRCA- or PALB2-mutated metastatic pancreatic cancer. In the past few years, new data have emerged to identify a subgroup of patients with pancreatic cancer who harbor mutations in DNA repair mechanism genes and have significant response to platinum-based chemotherapy. Recent publication of data from the Pancreatic Cancer Action Network initiative ‘Know Your Tumor’ showed that these mutations were identified in about 17% of patients with pancreatic cancer and demonstrated their improved survival with the use of platinum-based therapy in this setting.1 BRCA and PALB2 are the more common mutations in this cohort,” Dr. Dotan stated.

“The therapeutic benefit of PARP inhibitors as maintenance treatment after chemotherapy in these types of tumors has been shown in other tumors, including ovarian cancer, and led to this study in pancreatic cancer,” she continued. “In this interim analysis, rucaparib is reported to have significant progression-free survival and response rates with a favorable toxicity profile.
This maintenance treatment approach is highly valuable in providing patients with a treatment that will keep the disease in check without exposure to the toxicities associated with platinum-based chemotherapy. Despite the small number of patients, the results are encouraging and warrant further evaluation in a larger
clinical trial.”

Dr. Dotan noted that positive results of the phase III POLO study have been announced; this trial is evaluating the same approach in patients with pancreatic cancer who have germline mutations using the PARP inhibitor olaparib vs placebo.2

“As we await the full publications of these two studies, we should start thinking of conducting germline and somatic genetic testing in pancreatic cancer, to identify patients who fall into this category and may be candidates for DNA damage repair mechanism–targeted therapy,” Dr. Dotan suggested.

Additional Commentary

Colin D. Weekes, MD, PhD, Associate Professor at Harvard Medical School and Director of Medical Pancreas Cancer Research at Massachusetts General Hospital, Boston, also weighed in on the rucaparib study.

Colin D. Weekes, MD, PhD

Colin D. Weekes, MD, PhD

“This is a small study with encouraging results. It would be preliminary to make a substantial statement about the use of rucaparib as maintenance therapy The POLO study previously mentioned by Dr. Dotan is a randomized, placebo-controlled study conducted in a larger patient sample, thus providing a more definitive estimate of the benefit of the use of olaparib as maintenance therapy. Rucaparib warrants further study in a randomized study with careful selection of the control arm. We can infer from these two trials that the strategy of PARP inhibitor maintenance therapy may be a reasonable treatment strategy in selected patient populations.” 

DISCLOSURE: Dr. Dotan has received institutional research funding from Pfizer and honoraria from Boston Medical and Armo Biosciences. Dr. Weekes reported no conflicts of interest.

REFERENCES

1. Pishvaian MJ, Blais EM, Brody JR, et al: Outcomes in pancreatic adenocarcinoma patients with genetic alterations in DNA damage response pathways: Results from the Know Your Tumor Program. 2019 Gastrointestinal Cancers Symposium. Abstract 191. Presented January 18, 2019.

2. AstraZeneca: Lynparza significantly delayed disease progression as 1st-line maintenance treatment in germline BRCA-mutated metastatic pancreatic cancer. Available at www.astrazeneca.com/media-centre/press-releases/2019/lynparza-significantly-delayed-disease-progression-as-1st-line-maintenance-treatment-in-germline-brca-mutated-metastatic-pancreatic-cancer-26022019.html. Accessed April 26, 2019.


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The poly (ADP-ribose) polymerase (PARP) inhibitor rucaparib holds promise as maintenance therapy for advanced, platinum-sensitive, BRCA- or PALB2-mutated pancreatic cancer, according to an interim analysis of an ongoing phase II clinical trial presented at the 2019 Annual Meeting of the American...

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