Update: New drug approved for metastatic prostate cancer

Contents

UPDATE AT A GLANCE

What is this update about?

This update is about FDA approval of the drug Pluvicto for treating people with metastatic castration-resistant prostate cancer (mCRPC). The FDA also approved a drug called Locametz that can be used with imaging to identify patients who will likely benefit from treatment with Pluvicto.

Why is this update important?

Metastatic castration-resistant prostate cancer remains incurable, although many types of drugs delay progression and prolong life.

Pluvicto (177Lu-PSMA-617) is a targeted therapy drug that delivers radiation directly to tumor cells that express a protein known as PSMA. PSMA (also known as prostate-specific membrane antigen) is found at low levels in normal prostate cells but it is found at high levels in some prostate cancer cells. Pluvicto works on tumor cells that have increased PSMA.

The FDA also approved Locametz (Ga 68 PSMA-11) to detect PSMA levels in prostate cancer cells that have spread throughout the body. For more information on the approval of this imaging drug, read our XRAY review here. Imaging with Locametz can determine if a person’s cancer is likely to respond to Pluvicto.

Study findings

The FDA approval was based on the results of the VISION trial. VISION compared patients who were treated with Pluvicto and protocol-permitted standard care or protocol-permitted standard care alone. Standard-care therapy that was permitted included approved hormonal treatments (including abiraterone and enzalutamide), bisphosphonates, radiation therapy, denosumab, or glucocorticoid at any dose. Standard-care excluded chemotherapy, immunotherapy, radium-223 (223Ra), and investigational drugs. All the participants had prior treatment with an androgen receptor pathway inhibitor and chemotherapy and had tumors that expressed high levels of PSMA. High levels of PSMA were defined as at least one PSMA-positive metastatic lesion and no PSMA-negative lesions. PSMA-positive status was determined with the use of -68 (68Ga)–labeled PSMA-11 (68Ga-PSMA-11) PET–CT imaging.

Patients treated with Pluvicto had significantly improved overall and progression-free survival. Among patients treated with Pluvicto plus standard of care:

• Overall survival was 15.3 months compared to 11.3 months for patients treated with standard of care alone.
• Progression-free survival was 8.7 months compared to 3.4 months for patients treated with standard of care alone.

Almost 57 percent of participants who were treated with Pluvicto had an adverse event of grade 3 or higher compared to 38 percent of participants who were treated with standard of care alone. Garde 3 adverse events were defined as severe or medically significant but not immediately life-threatening. The most common adverse events were:

• Fatigue
• Dry mouth
• Nausea
• Anemia
• Decreased appetite
• Constipation

However, participants who were treated with Pluvicto did not report that their quality of life was adversely affected.

Strengths and limitations

Strengths

• The VISION trial included almost 600 participants.
• The imaging criteria that was used in this trial allowed patients with PSMA-positive metastatic castration-resistant prostate cancer to receive life-extending therapy on the basis of only one PET scan plus conventional imaging.

Limitations

• Adverse events were defined as occurring during the treatment period for up to 30 days after the last dose of Pluvicto or standard-of-care treatment. The 30-day post-dose period for such adverse events may have led to underestimating adverse events.
• Most (87%) of enrolled patients were white.
• The study was not blinded or placebo controlled so many patients left the study if they didn’t get Pluvicto.
   

What does this mean for me?

In most patients with mCRPC, metastatic lesions are positive for PSMA. Treatments like Pluvicto are begin developed to target prostate cancer cells while sparing healthy cells.

If you have been diagnosed with mCRPC and have previously been treated with and androgen receptoro pathway inhibitor and chemotherapy, then you may be eligible for additional imaging with Locametz to see if you would benefit from treatment with Pluvicto. 

References

FDA approves Pluvicto for metastatic castration-resistant prostate cancer. www.fda.gov, March 23, 2022.

Sartor O, de Bono J, Chi KN, Fizazi K, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103. Epub 2021 Jun 23.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board before publication to assure scientific integrity.

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posted 5/10/22