FDA Approves Gallium-68 PSMA-11 for Prostate Cancer
FDA Approves Gallium-68 PSMA-11, the First of the Revolutionary PSMA Drugs for Use with PET Scans to Detect Prostate Cancer Metastases and Recurrence
After years of anticipation, the FDA has finally approved the first PSMA drug to be used with PET scans to detect metastatic prostate cancer and local recurrence. The sensitivity and specificity of PSMA-PET is leaps and bounds above its predecessors and can detect metastases with a PSA of less than 1.0 in both bone and soft tissues, thereby eliminating the need for more than one body scan. (The use of multi-parametric MRI to characterize the gland itself is still relevant for newly diagnosed patients.)
The FDA approved PSMA-PET scans for patients with initially diagnosed prostate cancer when metastatic spread is suspected and for previously treated patients with a suspected recurrence detected by a rising PSA. In PCRI nomenclature, these two indications include patients in the Teal (intermediate-risk), Azure (high-risk), Indigo (relapsed), and Royal (advanced) categories. Although it has not yet FDA approved for men with Sky (low-risk) disease, there may also be a useful application for older men on active surveillance with a rising PSA for whom biopsies may be risky. In the 940 men who were investigated in the United States, there were zero instances of serious adverse events. Moreover, no serious issues have been discovered in other countries like Germany, where the scan has already been in use for five years.
Consistently, studies from around the world have found that the information gathered by PSMA-PET scans have resulted in changes to treatment plans that optimized the chance of achieving a cure or remission and/or prevented side effects from an inappropriate treatment in a significant percentage of cases (~40-75%). Some examples of situations where PSMA-PET would make an important difference would be:
In the event of a recurrence, a PSMA-PET scan can determine much more accurately whether the relapse is confined to the prostate and should be treated locally, or whether it has spread to other parts of the body and needs to be treated with spot radiation, hormone therapy, and/or cytotoxic chemotherapy.
In the event that only one or a few metastases are discovered, known as “oligometastatic disease,” a patient may benefit—and may even achieve remission—from having those lesions treated with radiation. In the past, by the time a scan had discovered metastases, it would have likely been too widespread to treat with radiation.
A newly diagnosed patient may have favorable predictive features (e.g., PSA, Gleason, tumor volume) that would, before PSMA, indicate short-course adjuvant hormone therapy alongside radiation (4 months), but the discovery of metastatic disease with PSMA would instead suggest a need for more intense therapy to improve the chance of cure or durable remission, for example, long-course hormone therapy (18 months) and/or the addition of second-generation hormone therapy or cytotoxic chemotherapy. Conversely, the absence of metastases on a PSMA-PET scan could—in some cases—spare one from systemic therapy that, in the past, would have been indicated based on the percentage likelihood of the existence of metastases rather than hard evidence.
More than improving staging and thus refining treatment plans, the approval of Gallium-68 PSMA-11 also anticipates the arrival of “theranostic treatments” like Lutetium-177, which is an injectable form of radiation that binds to the same PSMA agents used for the PET scan to treat prostate cancer metastases in the bones and soft tissues. It has already been in use in Australia and Germany for several years. Additionally, a new immunotherapy, “BiTE” uses PSMA and is in the early stages of investigation.
The approval of the gallium-68 PSMA-11 PET scan will be a true game-changer, and we are anticipating that it will become the standard of care and will be covered by insurance. The gallium-68 PSMA-11 agent is also easier to produce than the next best scanning agent, Fluciclovine F18 (a.k.a Axumin), and will hopefully soon be widely available across the country. This development will remove much of the ambiguity of prostate cancer staging and will certainly result in better outcomes for many men with prostate cancer.