PyL Imaging Agent Detects Lesions Outside the Prostate in a Phase 2/3 Trial

In a Phase 2/3 OSPREY clinical trial aimed at examining its diagnostic accuracy, 18F-DCFPyl (PyL), a new imaging agent for positron emission topography (PET) scans, can accurately detect prostate cancer lesions outside the prostate, whether in nearby lymph nodes or in distant locations, clinical trial data show. The tracer — developed by Progenics — is a second generation fluorine 18-labeled small molecule that targets the prostate-specific membrane antigen (PSMA) protein, present at high levels in prostate cancer cells. Once bound to cancer cells, the radioactive fluorine serves as a signal for PET scans, making it possible to obtain an image showing the location of these cells.

Results from a Phase 2/3 trial examining PyL’s safety and accuracy were recently presented orally at the 2019 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting in Anaheim, California.

The completed OSPREY Phase 2/3 trial included 385 men either with high-risk prostate cancer who had been referred for radical treatment — surgical removal of the prostate and lymph nodes — and assigned to group A, or those who had radiological evidence of recurrent or metastatic cancer and were eligible for biopsy (group B).

To determine the safety and accuracy of PyL, these men underwent PET scans a couple of hours after the imaging agent was released into their bloodstream. Imaging results were then compared to specimens obtained during surgery for group A and biopsies from group B. Three independent readers examined the PET scans.

In group A, the scans led to very few false positives, but a sizable proportion of lesions identified as negatives were actually false negatives. (False positives indicate the presence of cancer at locations it’s not, and false negatives detect no cancer in locations where it exists.) In group B, imaging scans were much more accurate, with very few false negatives identified. This high specificity was seen across regions, both in pelvic lymph nodes and in more distant sites.

“[These results] underscore the power of PyL to accurately detect prostate cancer, including high risk and biochemically recurrent disease where more precise imaging can change treatment decisions,” Asha Das, MD, chief medical officer of Progenics, said in a press release. PyL was well-tolerated, with no serious adverse events related to the agent. Most frequent side effects were altered or unpleasant taste sensations and headache. “With our PSMA-targeted approach, we have the potential to detect small nodal and distant metastases, even in men with low PSA scores. We believe that PyL could transform how prostate cancer is detected, monitored, and treated,” Das said.

PyL is now being assessed in the open-label CONDOR Phase 3 study (NCT03739684) in about 200 men suspected of prostate cancer recurrence, who have had negative or equivocal findings on conventional imaging. The trial is currently recruiting at sites across the U.S. and in Quebec. Sites in the U.S. can be found in California, Connecticut, Florida (Moffitt Cancer Center), Iowa, Maryland (Johns Hopkins), Michigan, Missouri, New York, Pennsylvania, and Wisconsin.

The article above was first published in Prostate Cancer News Today, July 25th, 2019.

 

68-Gallium PSMA PET Scan Better Than Axumin in Detecting Cancer Recurrence

Among men suspected of having prostate cancer recurrence after surgery, the radiotracer 68Ga-PSMA-11 is better at detecting the cancerous lesions and provides better agreement among experts than the standard Axumin (18F-fluciclovine) tracer, a Phase 2 trial shows.

The results were presented at the 2019 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, held June 22–25 in Anaheim, California. The communication was titled “68Ga-PSMA-11 PET/CT detects prostate cancer at early biochemical recurrence with superior detection rate and reader agreement when compared to 18F-Fluciclovine PET/CT in a prospective head-to-head comparative phase 3 study.”

Radical prostatectomy — surgery to remove the prostate and surrounding tissues — is among the most common treatment options for prostate cancer. However, up to 40% of patients see their PSA levels increase after surgery. This process, called biochemical recurrence, indicates the return of cancer.

Doctors use various imaging methods to estimate the size and location of recurrent tumors before starting treatment. However, traditional techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and bone scans often fail to detect small tumors, especially at the early stages of biochemical recurrence, when PSA levels are low.

Positron emission tomography/computed tomography (PET/CT) is a highly sensitive imaging method that uses radiotracers — molecules that target specific cellular components, linked to small amounts of radioactive materials — and a special camera and computer to evaluate the function of different tissues. Researchers have developed radiotracers that specifically label components of prostate cancer, thus allowing its detection at earlier stages.

Axumin, by Blue Heart Diagnostics, is a radiotracer indicated to identify suspected sites of prostate cancer recurrence. It is a synthetic amino acid that preferentially enters prostate cancer cells due to their increased amino acid transport, labeling them with the radioisotope fluorine-18.

On the other hand, the 68Ga-PSMA-11 tracer consists of a molecule that binds the prostate specific membrane antigen (PSMA) labeled with the radioactive element gallium, Ga. This radiotracer can detect prostate cancer safely and accurately, but has not been compared with standard Axumin in clinical trials.

The Phase 2 trial (NCT03515577) compared the efficacy of PET/CT using either 68Ga-PSMA-11 or Axumin at detecting prostate cancer in 50 men with early biochemical recurrence, whose PSA levels ranged between 0.2 and 2 ng/mL.

Participants underwent Axumin PET/CT within two weeks before or after 68Ga-PSMA-11 PET/CT, and results were assessed by three independent imaging experts.

The study’s main goal was to compare the detection rates by patient and region. Secondary measures included detection rates according to initial PSA levels, the accuracy of each method, and agreement among readers.

Researchers found that the 68Ga-PSMA-11 tracer helped the experts identify prostate cancer lesions in significantly more patients (56%) than Axumin (23%). The PSMA tracer also identified more lesions by region — 30% versus 8% in the pelvic area, and 16% versus 0% in the extra-pelvic area.

Finally, readers agreed more on the results of this tracer, both by patient and by region.

“In patients with biochemical recurrence and low serum PSA levels after radical prostatectomy, PSMA PET/CT has higher detection rates and better reader agreement than Axumin,” researchers concluded. “Therefore, PSMA PET/CT should be the imaging modality of choice in patients with early biochemical recurrence.”

Published on line on July 8th, 2019 in Prostate Cancer News Today.

Strength for the Fearful; Part One

Boca Pass, looking toward Cayo Costa, Boca Grande, FL; Photo: BJ Gabrielsen

This website is normally directed toward men with prostate and other medical issues. But I found this blog and the succeeding one to be very applicable to many other life’s problems.

Isaiah 41:10 cites one of the clearest and most powerful promises God makes to those who have put their trust in Him as His servants. God says “Fear not, for I am with you; Be not dismayed, for I am your God. I will strengthen you, yes I will help you, I will uphold you with My righteous right hand.”

When one of God’s people is seeking an anchor in turbulent times (e.g. medical issues), this is the right passage for the job. Here, Isaiah writes about the source of a Christian’s strength. In verse 10, the Lord promises strength, help and protection. Moreover, He gives two commands; “Do not fear” and “Do not anxiously look about you.”  Even as Christians, our enemy Satan as well as our own minds, can induce subtle and successful traps through the art of distraction. The evil one knows that fear can choke faith. In fact, fear and faith cannot occupy the same space simultaneously. He works hard through our mind to make unsettling circumstances a person’s sole focus. Once a believer’s attention is diverted from God, natural human tendencies take over. In the absence of prayer and worship, anxiety and doubt grow unobstructed.

Staying focused on the Lord can be hard. Our flesh prefers to seek security by thinking through all possible angles. Our tendency is to weigh what we think could happen against what “experts” say will happen, and then to evaluate possible ways of preventing our worst fears from coming true. Instead of becoming more confident, we begin to realize how powerless we are. Thankfully, we serve an almighty God who says, “Surely I will help you” (v.10). We can count on Him and agree with the Apostle Paul, “for when I am weak, then I am strong.” (2 Corinthians 12:10.)

By focusing on our circumstances, we’re actually choosing to feel anxiety and doubt. But these emotions don’t belong in a believer’s daily life. Instead, let’s decide to trust in the promises God has given us. He’s filled His Word with scriptural anchors (see Scriptual Medicines) to keep His children steady in the faith. To be continued in Part Two, “How to Have Two-Fold Peace.”

(A portion of the above was adapted from the “In Touch” Devotional by Dr. Charles Stanley, May 29th, 2019.)

 

 

Part Two: How to Have Two-Fold Peace

Charlotte Harbor, Bokeelia, FL; Photo: BJ Gabrielsen

God’s promises e.g. Isaiah 41:10, apply to us who have a personal relationship with Him through faith in Jesus Christ. Within the Christian experience, there is a two-fold sense of peace. We are promised the peace of God when we commit our troubles and requests to Him, peace that will guard our heart and mind as we abide in Christ. “Be anxious for nothing, but in everything by prayer and supplication (request), with thanksgiving, let your requests be made known to God; and, the peace of God, which surpasses all understanding, will guard your hearts and minds through Christ Jesus.” (Philippians 4:6-7).

But we can only experience the peace of God because we have peace with God. “Having been justified by faith” (declared  or made righteous in the sight of God,) “we have peace with God through our Lord Jesus Christ.” (Romans 5:1). Both types of peace are important, but there is an order: first, peace with God; then the peace of God. Both are gifts of God’s grace, worthy of praise and thanks to Him.

If you are seeking God’s peace in your life, make sure you have peace with God first. Both are ours through faith in Christ. When we lack the peace of God, we should turn to our peace with God.

The above was published May 29th, 2019 in the devotional “Turning Point” by Dr. David Jeremiah.