New drug shows encouraging survival in pancreatic cancer

A clinical trial testing a new drug in pancreatic cancer had promising initial results, report researchers from the University of Michigan Rogel Cancer Center. A phase 1 clinical trial looked at AZD1775, an inhibitor designed to block an enzyme called Wee1, which plays a role in DNA damage repair. The trial builds on almost 20 years of research at U-M focused on improving the treatment of pancreatic cancer that is too advanced for surgery.

Radiation and the chemotherapy drug gemcitabine, which are standard treatment for pancreatic cancer, both work by causing damage to DNA. But pancreatic cancer has a way of repairing that damage, which limits how effective these therapies can be. Rogel Cancer Center laboratory researchers, led by Meredith Morgan, Ph.D., found AZD1775 prevents pancreatic cancer from protecting itself against the effects of radiation and gemcitabine, while leaving normal cells relatively unaffected.

"If we can disable the DNA damage response in pancreatic cancer cells, it might eliminate treatment resistance and sensitize the cancer to the effects of both radiation and chemotherapy," says lead study author Kyle Cuneo, M.D., associate professor of radiation oncology at Michigan Medicine.

The trial enrolled 34 patients with locally advanced pancreatic cancer. Patients received AZD1775 in addition to radiation and gemcitabine. The goal of the study was to determine the maximum tolerated dose of AZD1775 in this combination. In the process, the researchers also found that this combination resulted in better than expected overall survival.

Pancreatic cancer is particularly known for spreading to distant parts of the body, part of the reason overall five-year survival is just 9%.

"If we're ever going to cure pancreatic cancer, we're going to need effective systemic treatment as well as local therapy. Our data suggests that AZD1775 can do both," says senior study author Ted Lawrence, M.D., Ph.D., Isadore Lampe Professor and chair of radiation oncology at Michigan Medicine.

The median overall survival in the study was 22 months, with no progression for a median of nine months. A previous study using gemcitabine alone in a similar group of patients found overall survival of 12-14 months.

"Adding AZD1775 to radiation and gemcitabine was relatively well tolerated with encouraging survival results. Further studies with this promising combination are needed," Cuneo says.

Cuneo KC, Morgan MA, Sahai V, Schipper MJ, Parsels LA, Parsels JD, Devasia T, Al-Hawaray M, Cho CS, Nathan H, Maybaum J, Zalupski MM, Lawrence TS.
Dose Escalation Trial of the Wee1 Inhibitor Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer.
J Clin Oncol. 2019 Aug 9:JCO1900730. doi: 10.1200/JCO.19.00730.

Most Popular Now

AstraZeneca divests rights for Losec to Cheplaphar…

AstraZeneca has agreed to sell the global commercial rights, excluding China, Japan, the US and Mexico, for Losec (omeprazole) and associated brands to Cheplapharm Arznei...

Bayer, Brigham and Women’s Hospital, and Massachus…

Bayer and Partners HealthCare's founding members Brigham and Women's Hospital (BWH) and Massachusetts General Hospital (MGH) today announced the launch of a joint lab to ...

Amgen announces positive results from two Phase 3 …

Amgen (NASDAQ:AMGN) today announced that the results of a prespecified interim analysis of an open-label, randomized, controlled global multicenter Phase 3 trial (2012021...

Cause of antibiotic resistance identified

Scientists have confirmed for the first time that bacteria can change form to avoid being detected by antibiotics in the human body. Studying samples from elderly patient...

Brilinta monotherapy in high-bleeding risk patient…

New data from TWILIGHT, a Phase IV independent trial (funded by AstraZeneca), showed that in patients at high-bleeding risk who underwent PCI and completed 3 months of du...

Novartis and Microsoft announce collaboration to t…

Novartis announced an important step in reimagining medicine by founding the Novartis AI innovation lab and by selecting Microsoft as its strategic AI and data-science pa...

Bayer inks deals with eleven startups under G4A Di…

Bayer announced today that the company has signed collaboration agreements with eleven digital health startups. As part of the program, Bayer will support these startup c...

Ian Read to retire as Executive Chairman of Pfizer…

Following its regularly scheduled meeting, the Board of Directors of Pfizer Inc. (NYSE:PFE) today announced that Executive Chairman of the Board Ian C. Read has chosen to...

Discovery of new source of cancer antigens may exp…

For more than a decade, scientist Stephen Albert Johnston and his team at Arizona State University's Biodesign Institute have pooled their energies into an often scoffed-...

Pharmacists provide patient value in team-based ca…

With inhaler in hand, Dr. Cheng Yuet went over every detail to make sure the patient understood how the drug would control their COPD symptoms. Dr. Yuet is proving what a...

Chinese activists protest the use of traditional t…

In the West, the number of people challenging scientific authority has been growing in past decades. This has, among other things, led to a decline in the support for mas...

AI and big data predict which research will influe…

An artificial intelligence/machine learning model to predict which scientific advances are likely to eventually translate to the clinic has been developed by Ian Hutchins...