The U.S. Food and Drug Administration (FDA) has granted priority review to Clovis Oncology’s application seeking approval of Rubraca (rucaparib) for treating men with recurrent metastatic castration (hormone)-resistant prostate cancer (mCRPC) and BRCA mutations.
Clovis submitted its application to the FDA in November, 2019. The priority review status will shorten Rubraca’s regulatory review for this indication to six months from the standard 10 months.
Nearly 12% of men with mCRPC have a mutation in the BRCA1 or BRCA2 genes, which are involved in DNA repair. These tumors rely on other DNA repair mechanisms — including those involving PARP enzymes that act as DNA damage sensors — to survive and grow. Thus, treatments that block PARPs’ activity (PARP inhibitors), such as Rubraca, are particularly effective in BRCA-mutated tumors. Rubraca is already approved for the treatment of several gynecologic tumors carrying BRCA mutations, and as a maintenance therapy regardless of BRCA mutations.
Rubraca’s new application was supported by data from the TRITON2 Phase 2 trial (NCT02952534), which is evaluating its safety and effectiveness in up to 360 mCRPC patients with mutations in BRCA genes or in other 13 DNA repair genes known to increase susceptibility to PARP inhibitors.
Besides eligible mutations, participants must have experienced disease progression after at least one but no more than two previous androgen-receptor targeted therapies and one prior taxane-based chemotherapy for their castration-resistant disease.
TRITON2’s main goals were to assess overall response rates in men with measurable disease, and the proportion of men who saw a reduction in the levels of prostate-specific antigen (PSA) — a biomarker of prostate cancer — after treatment. Secondary goals included duration of response, time to disease progression or death, overall survival, and safety measures.
Early positive data from TRITON2 led to Rubraca’s breakthrough therapy designation by the FDA for the treatment for mCRPC patients with BRCA mutations, a status intended to accelerate the therapy’s development and review. As of Feb. 28, 2019, 190 patients (98 with a BRCA mutation) had received Rubraca, with a median follow-up of 13.1 months. Among patients with BRCA mutations, results showed that 43.9% of those with measurable disease responded to treatment, and that 60% of these responses lasted at least 24 weeks. Also, 52% of patients had a confirmed PSA response (deemed as a 50% or greater reduction in PSA levels), which lasted a median of 5.5 months.
Rubraca’s safety profile was consistent with prior reports from TRITON2 and other trials, with the most common adverse events being fatigue (55.3%), nausea (49.5%), anemia (37.9%), decreased appetite (27.9%), transient increase in liver enzymes (24.7%), constipation (24.7%), vomiting (22.1%), and diarrhea (21.1%).
The preceding was an excerpt from Prostate Cancer News Today, Jan. 16th by Dr. Marta Figureiredo.
How do you react in a severe storm or if you receive bad news? Do you tense up with fear or do you recall words such as those in Psalm 107:28-30? “Then they cry out to the Lord in their trouble, and He brings them out of their distresses. He calms the storm, so that its waves are still. Then they are glad because they are quiet; so He guides them to their desired haven.”
Personally, the year 2019 was filled with medical challenges. In addition to my 24-year issue with prostate cancer, physicians speculated that I may have bladder cancer as well. When I received this news, I did indeed tense up with fear and uttered the following to God. “Why this too? Isn’t one type of cancer enough?” I discovered that when one gets bad news, it usually takes 2-3 days before the initial shock subsides and I can then more calmly refocus on God’s presence.
Life’s storms can either stunt or accelerate our spiritual growth. The determining factor is our reaction. Some people humbly cry out to the Lord, while others get angry or frustrated with Him and their circumstances. Still, others ignore God and try to figure things out on their own, seeking solutions in every place except God’s Word.
Turning away from the Lord results in a hardened heart for someone who does not have a personal relationship with Him; for a believer, turning away results in spiritual discipline. God wants us to be surrendered to His will whatever the occurrence, because if we are proud, doubting Him or self-reliant, then we aren’t useful for His glory and purpose for our lives. That is why God brings storms across our path- to teach us to fully rely on Him.
When the Lord allows adversity in your life, do you accept it as something designed for your good? Or do you try to bend God to conform to your own will? As difficult as they may be, storms are meant to produce godly character in us. In my own case, why was the storm of potential bladder cancer to be used for my good? After a period of intense questionning of God and His care for me, I was specifically led to Jesus’ prayer to His Father just prior to His crucifixion as payment for all our sins. In Mark 14:36. Jesus intensely prays, “Abba Father, all things are possible for You. Take this cup away from Me; nevertheless, not what I will but what You will.” After some days of struggle, first I likewise fully acknowledged to God that He has the power to eliminate any traces of cancer from my body. I may not witness many dramatic cancer healings today but God indeed has the power to do so if He desires. All things are possible for Him. Second, as in Jesus’ prayer, I pleaded that He take any vestiges of bladder cancer away from my body. Thirdly, and most importantly, I affirmed that even if cancer were to be found, I would trust His care and His will in my life. After a CT scan and a thorough visual examination of my bladder by my urologist, no cancer was revealed. Instead, I had some fragile blood vessels induced as a side effect of previous radiation therapy. Under God’s direction and ministry to me, I had weathered this storm and learned a valuable lesson to pattern my personal prayer to that of Jesus Himself when the next storm arises.
If you are unsure of a personal relationship with God through faith in Jesus, then this post might seem foreign to you. Coming to know God and His Son Jesus in a personal and unique way is the place to start.
A portion of the above was an excerpt from the January 8th, 2020 In Touch Ministries devotional by Dr. Charles Stanley.
Tumor samples from a prostate biopsy are graded (Gleason score) which is an indication of a tumor’s aggressiveness. The tumor grade reflects how far the cancer cells deviate from normal healthy cells. Gleason 6 cancer looks almost like normal prostate gland tissue while higher Gleason scores are indicative of more serious cancers. The Prostate Cancer Research Institute (PCRI) recently published an e mail video from Dr. Mark Scholz stating that in a survey of 26,000 men, it was concluded that surgically-proven Gleason 6 prostate cancer does not metastasize. Men diagnosed with grade 6 cancer should be followed by “watching” and not “treating”. In this study, 22 men with positive nodes were regraded to Gleason 7 or higher. If this study is applicable to your case, please be advised to discuss this video and its conclusions with your personal urologist or oncologist.
Blogger Dr. Bjarne (B.J.) Gabrielsen at Boca Grande Lighthouse, Charlotte Harbor, Punta Gorda, Southwest Florida Gulf Coast
I am a prostate cancer survivor since 1995. If you know of any men in your life who may have an interest in prostate cancer at any stage of disease, please inform them of this website, Godandprostate.net, .com, .org or .info. As blogs are posted, readers can receive them automatically by e mail by simply inserting their e mail address in the indicated space on the right side of the home page. Posts focus on all aspects of prostate cancer as well as encouraging commentaries which we all need at one time or another. Comments on any specific post are always welcome. Remember, as men, we are all in this together and God desires to play a central role in our lives. While I am not a medical doctor, I received my doctorate in organic chemistry at the State University of New York – Stony Brook. My career was evenly distributed between academia (Wagner College, NY and the University of Florida, Gainesville, FL) and government (NCI). I retired from the National Cancer Institute (NCI), National Institutes of Health (NIH) as Senior Advisor in antiviral and antitumor Drug Discovery and Development.
Every year, the PCF publishes an electronic guide providing information on all aspects of prostate cancer. The chapters covered are as follows.
- General information including diagnosis, symptoms, risk factors, and medical basics.
- Information for the newly diagnosed, including detection, diagnosis and treatment selection.
- Treatment options for localized or locally advanced prostate cancer. These include active surveillance, surgery, various radiation modalities, and other experimental therapies for localized prostate cancer.
- Living with and after prostate cancer including sections on quality of life, recurrence, urinary, bowel and sexual function, diet, exercise and lifestyle changes.
- What to do if one’s PSA starts to rise. Topics include local treatments for recurrent cancer, therapies for advanced recurrent or metastatic cancer, hormone-resistant cancer, non-hormonal therapy options and side effects from various treatments for advanced prostate cancer.
- Cutting edge developments in prostate cancer research including precision medicine, PARP inhibitors, immune checkpoint inhibitors, CAR T cells and vaccines.
- Information for families of prostate cancer patients including future risk, genetic testing and screening and prevention.
- Here is a link to the most recent edition of the annual PCF prostate cancer guide.
At a recent meeting of a prostate cancer support group, a list of internet informational resources were listed. Upon checking each one, I have found the following to be most informative and current. For a complete listing, see the section entitled Medical Resources on this website.
- The National Cancer Institute (NCI) of the National Institutes of Health (NIH) in Bethesda and Frederick, Maryland have a site entitled cancer.gov.
2. For a searchable compilation of active and recruiting clinical trials, see clinicaltrials.gov.
3. The Prostate Cancer Foundation is a valuable source of information about all aspects of prostate cancer. See pcf.org.
4. Likewise, the Prostate Cancer Research Institute is also a valuable source. See prci.org.
5. I had never seen the following before, but it deserves a listing. See yananow.net.
Progenics Pharmaceuticals’ PyL, a new imaging agent for positron emission tomography (PET) scans, can accurately detect the location of recurrent prostate cancer lesions, according to data from the Phase 3 CONDOR clinical trial.
“There is a need for improved diagnostics for prostate cancer to replace conventional imaging tests that have limited performance characteristics, especially in men with biochemical recurrence of their disease,” said Barry Siegel, MD, CONDOR’s principal investigator at the Mallinckrodt Institute of Radiology at Washington University School of Medicine clinical site.
PyL (18F-DCFPyl) is a tracing agent composed of DCFPyL, a small molecule that specifically targets the prostate specific membrane antigen (PSMA) protein — present at high levels in prostate cancer cells — coupled with a radioactive compound labelled with fluorine 18. After PyL is injected intravenously into the patient, it travels through the blood and accumulates at prostate cancer sites, making them “light up” during PET scans. PyL has the potential to allow clinicians to detect very small lesions that are currently missed with conventional imaging methods, so can they determine if the disease has returned or spread to distant organs and adjust treatment plans accordingly.
The open-label CONDOR study (NCT03739684) evaluated whether PyL could safely, successfully, and accurately detect new prostate cancer lesions in 208 men suspected of prostate cancer relapse. These suspicions, which were based on biochemical relapse — rising levels of prostate-specific antigen (PSA), a biomarker of the disease — were accompanied by negative or ambiguous findings on conventional imaging scans.
Participants were recruited, dosed, and imaged with PyL at 14 sites in the U.S. and Canada. CONDOR’s primary goal was to assess the predictive value of PyL in detecting the right location of new cancer lesions that confirmed the disease had returned. For that, three blinded, independent researchers compared the results of PyL PET scans with those of confirmatory biopsy or surgery, conventional imaging, and/or changes in PSA levels following radiation therapy of PyL-suspected lesions, performed within 60 days after PyL imaging. The study’s secondary goal was determining the percentage of patients whose treatment plan was changed based on PyL imaging results.
Results showed that the trial met its primary goal, with PyL imaging detecting at least one posteriorly confirmed new lesion in 84.8% to 87% of the cases. This exceeded by far the 20% threshold established by the FDA “for the trial to be deemed a success,” reflecting “the impactful clinical utility of PyL imaging.”
As far as safety, the imaging agent was well-tolerated, consistent with data from the previous Phase 2/3 OSPREY clinical trial (NCT02981368). The most frequently reported adverse side effect (in 1.9% of patients) was headache, and one man had a serious immune reaction (hypersensitivity) to PyL.
“The high positive predictive value demonstrated in this study reflects the clinical utility of PSMA-targeted PET imaging agents providing actionable information to physicians to guide treatment plans and improve disease management of one of the most prevalent cancers in the U.S.,” Siegel said.
“The positive results of our Phase 3 CONDOR trial reinforce our belief in the potential of PyL to enable better physician treatment decisions and, ultimately, improve patient outcomes,” David Mims, Progenics’ interim CEO, said in a press release. The company plans to submit a new drug application for PyL to the U.S. Food and Drug Administration in the second half of this year, according to Mims.
Material cited above was received on January 13th in the Prostate Cancer News Today Weekly Digest to which I recommend a subscription.