Rubraca Granted FDA Priority Review for Advanced Prostate Cancer in Men with BRCA Mutations

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.

Responding to Life’s Storms

God provides for all His creatures; photo: BJ Gabrielsen

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.

A Clinical Trial for Men With Low – Intermediate Risk Prostate Cancer Considering Radiation Therapy.

The National Cancer Institute (NCI) is sponsoring a clinical trial at many locations comparing two types of radiation therapy, stereotactic body radiation therapy (SBRT) with intensity-modulated radiation therapy (IMRT). The former is administered in less than two weeks while the latter is given in five weeks. The aim of the trial is to compare cure rates and side effects. The following video by Dr. Mark Scholz, Executive Director of the Prostate Cancer Research Institute (PCRI) describes the trial now recruiting patients.