Advanced prostate cancer has been an early testing ground for radiopharmaceuticals. In 2020, the FDA approved a diagnostic drug that, when injected into the bloodstream, can be imaged by PET scanning to indicate the presence of PSMA-positive prostate
cancer lesions in the tissues of the body. (PSMA, or prostate-specific membrane antigen, is a protein found in large amounts on prostate cancer cells.) The images can show whether prostate cancer has spread to other parts of the body.
As an experimental treatment, researchers at the drug company Novartis developed a radiopharmaceutical drug called Lu177-PSMA-617 that targeted PSMA and was delivered via the bloodstream to men with advanced prostate cancer. Reporting on a phase 3 study
in June 2021, the study team reported that the treatment improved the time it took for the cancer to progress and the overall time that patients were able to live with cancer.
"It is impressive because it is targeted therapy, and most other prostate cancer drugs aren't targeted," said Mary-Ellen Taplin, MD, a prostate cancer specialist and chair of the Executive Committee for
Clinical Research at Dana-Farber. "I am thrilled to have another option for patients who are in need of effective treatments." Taplin says the added survival benefit — about four months on average — "shows that this treatment, while effective, can
be improved upon to bring more benefit to our patients." This radiopharmaceutical drug could show more advantages in patients with earlier stages of the disease or as part of combination therapy. These approaches are being studied actively in clinical
Using a radioactive substance that can be imaged to locate a cancer in the body, coupled with another radiotherapeutic drug to treat it is known as theranostics.
"The field of theranostics has seen substantial growth recently with the approval of several new agents," said Ross Berbeco, PhD, the director of medical physics research in Radiation Oncology.
"At Dana-Farber Cancer Institute and Brigham and Women's Hospital, it is emerging as a potentially important addition to our cancer treatment options."
Jacene, who is also assistant chief of nuclear medicine molecular imaging at Brigham and Women's, says several trials of radiopharmaceuticals are underway at Dana-Farber. She says clinical trials may be suggested by medical oncologists in treatment centers
or in nuclear medicine. "In either instance, together the treatment center team and our nuclear medicine team evaluate the proposal to determine if it is something that fits within our portfolio and makes scientific sense." Through this approach,
Dana-Farber participated in a pivotal phase 3 study that led to the approval of Lu177-dotatate, as well as the phase 3 study of Lu177-PSMA-617.
One recently opened trial is a phase 1 study that uses an alpha-particle-emitting isotope drug to target IGF-1R (the insulin-like growth factor-1 receptor) on solid tumor cells, including prostate, colorectal, and adrenocortical cancers. "You have to
get imaged first, and if your tumor has a high enough level of IGF-1R you can go onto the next phase getting treated," explains Jacene. "If it's there, we can treat it."
Another trial is testing a combination of radium-223 dichloride and cabozantinib, a targeted inhibitor drug, in patients with advanced kidney cancer that has metastasized to bones.
In collaboration with Jennifer Chan, MD, MPH, director of the program in carcinoid and neuroendocrine tumors at Dana-Farber Brigham Cancer Center, the nuclear medicine team is participating in a cancer cooperative
group clinical trial for patients with neuroendocrine tumors. The patients receive the radiopharmaceutical Lu177-dotatate, along with triapine, a drug that primes cancer cells to be more responsive to radiation. Researchers expect combinations of
radiopharmaceutical and other types of drugs, such as targeted kinase inhibitors and immunotherapy agents, to be potentially more effective than radiopharmaceutical agents alone.
Despite the potential and advantages of radiopharmaceutical treatment, the field is still in its early days. It has been tested in only a few of the many types of cancer that exist, and much remains to be explored in terms of targets that can be attacked
with radioactive substances.
Another challenge that researchers are grappling with is dosimetry — calculating how much of a radioactive drug to give to an individual patient and for how long. Jacene says that greater study of dosimetry should help personalize therapy for patients.
In addition, the need for large numbers of specialized practitioners and staff qualified to handle and administer radiopharmaceuticals imposes limits on how widely the treatments will be used in the near future.
"I think, and truly hope, the field continues to grow, but right now it's mainly major medical centers and academic sites that are set up to use radiopharmaceutical therapy," Jacene says. However, she says, the field is becoming better known and this
extends to patient groups as well.
"I attended a prostate cancer support group last month and I was asked extremely important and tough questions [about the therapy] for 30 minutes," Jacene says.
To stimulate research and collaboration on promising new radiopharmaceuticals, the National Cancer Institute (NCI) in 2019 launched the Radiopharmaceutical Development Initiative,
headed by Charles Kunos, MD, PhD, of NCI's Cancer Therapy Evaluation Program. He predicts that this new targeted approach, while it won't eliminate conventional radiation therapy, "is going to transform radiation oncology in the next 10 to 15 years."