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Adavosertib (AZD1775) with Gemcitabine and Radiation for Locally Advanced Pancreatic Cancer: An Interview With Kyle C. Cuneo, MD

Kyle C. Cuneo, MD.

Pancreatic cancer is one of the most aggressive forms of cancer, and owing to limited treatment options, it has one of the lowest survival rates. While patients are commonly treated with radiation therapy, there is a need to develop alternative treatment options that can improve the efficacy of radiation, reduce tumor progression, and increase survival. In a recent study, Kyle C. Cuneo, MD, and colleagues evaluated the safety and tolerability of adavosertib (AZD1775), an inhibitor of the Wee1 kinase, in combination with radiation and gemcitabine, a chemotherapy drug. In this interview with i3 Health, Dr. Cuneo discusses the promising benefits that this treatment has to offer for patients with locally advanced pancreatic cancer.

What are some of the most challenging aspects of treating patients with locally advanced pancreatic cancer?

Kyle C. Cuneo, MD: Patients with locally advanced pancreatic cancer often have many symptoms at the time of diagnosis, including weight loss, poor appetite, and nausea. Treatments such as chemotherapy and radiation therapy can make these symptoms worse in the short term. Additionally, progress in treating this disease has been slow compared to that of many other cancers, and better treatments are needed.

How does AZD1775 in combination with gemcitabine and radiation compare with current treatments of locally advanced pancreatic cancer?

Dr. Cuneo: The primary purpose of our study was to identify a safe and tolerable dose of AZD1775 to combine with gemcitabine and radiation. The radiation treatment and gemcitabine treatment were performed in a very similar manner to our standard course of therapy offered to patients not in the study; the only difference was adding the experimental drug. We found that this combination of AZD1775 with gemcitabine and radiation has a similar tolerability to our standard treatment. Additionally, we were encouraged by how well some of the patients did; the survival was approximately 50% longer than what we have observed in our prior studies in a similar patient population. Further studies are needed to confirm the efficacy of this combination.

How do you foresee the treatment of locally advanced pancreatic cancer evolving?

Dr. Cuneo: Currently, the management of patients with locally advanced pancreatic cancer varies across both the United States and the world. Historically, chemoradiation has been used to treat the local tumor and the involved nodes. However, a large trial published a few years ago showed minimal benefit in adding radiation to chemotherapy. This trial, as well as most others, did not use modern radiation techniques like intensity-modulated radiation therapy (IMRT) and daily image guidance. Modern radiation techniques allow us to limit the dose to adjacent organs that are at risk, making the therapy more tolerable and effective for patients. Many centers offer chemotherapy alone for patients with locally advanced pancreatic cancer because of the recent studies showing the minimal benefits of adding radiation. The problem is that because no solid tumors are cured with chemotherapy alone, the treatment is essentially palliative in nature, whereas many types of cancers are cured with radiation therapy. New drugs like AZD1775 have the potential to make local therapy with radiation more effective. With improved systemic therapy, local control of the primary disease will become more important in patients who are not able to have surgery.

Do you have any words of advice for oncologists treating patients with locally advanced pancreatic cancer?

Oncologists should enroll their patients on clinical trials. This is the only way we will improve outcomes in patients with this disease.

About Dr. Cuneo

Kyle C. Cuneo, MD, is an Associate Professor in the Department of Radiation Oncology at the University of Michigan, where he performs clinical and translational research and serves as the principal investigator of clinical trials in pancreatic cancer, colorectal cancer, and hepatocellular carcinoma. His research focus is on gastrointestinal malignancies and adaptive radiation therapy, including the development and testing of radiation sensitizers.

For More Information

Cuneo KC, Morgan MA, Sahai V, et al (2019). 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. [Epub ahead of print] DOI:10.1200/JCO.19.00730

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily represent those of i3 Health. 

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