ESSA Pharma presented new preclinical data on ESSA’s lead Investigational New Drug candidate at the 2019 American Urological Association Annual Meeting. The studies demonstrate that, pre-clinically, EPI-7386: Displays similar in vitro IC50 potency compared to the ‘lutamide class of antiandrogens in an in vitro androgen receptor inhibition assay; Shows in vitro activity in several enzalutamide-resistant prostate cancer cell models in which enzalutamide is resistant; Exhibits a favorable metabolic profile across three preclinical animal species, which suggests that EPI-7386 will have high exposure and a long half-life in humans; Provides similar antitumor activity to enzalutamide in the enzalutamide-sensitive LNCaP prostate cancer xenograft model; Provides superior antitumor activity to enzalutamide, as a single agent or in combination with enzalutamide, in the enzalutamide-resistant VCaP prostate cancer xenograft model; AR inhibition with both an N-terminal domain inhibitor and a ligand binding domain inhibitor, induces deeper and more consistent anti-tumor responses in the enzalutamide-resistant VCaP xenograft model.
Sunday, May 5, 2019
Neurocrine presents data analysis from two Phase III studies of opicapone
Neurocrine announced the presentation of a data analysis from two Phase III studies of opicapone, a novel, once-daily, oral, selective, peripherally-acting catechol-O-methyltransferase inhibitor for the treatment of Parkinson’s disease. The analysis found that treatment with opicapone 50 mg, added to levodopa, resulted in a significant and sustained increase in ON time without troublesome dyskinesia, in Parkinson’s disease patients with motor fluctuations. In addition, more than 60% of patients treated with once-daily opicapone 50 mg achieved greater than or equal to a one-hour increase from baseline in total ON time at week 14/15. The analysis, which included data from more than 900 patients in the double-blind, placebo-controlled Phase III BIPARK-1 and BIPARK-2 studies, was highlighted as an oral session at the 2019 American Academy of Neurology Annual Meeting in Philadelphia. The data presentation highlighted statistically significant increases in absolute ON time without troublesome dyskinesia from baseline to the week 14/15 endpoint in both the BIPARK-1 and BIPARK-2 studies. The improvements in ON time without troublesome dyskinesia were sustained in all patients treated with opicapone in the one-year long-term open-label extension studies, with an average increase from baseline of 2.0+/-2.6 hours in BIPARK-1 and 1.8+/-3.2 hours for BIPARK-2. In addition, a significantly higher percentage of patients treated with opicapone 50 mg had an increase in total ON time of an hour or longer at week 14/15 in both BIPARK-1 and BIPARK-2. Pooled safety data from the double-blind opicapone-treated population showed that 17.4% patients treated with opicapone reported dyskinesia as a treatment-emergent adverse event versus 6.2% in placebo-treated patients. Only 1.9% of opicapone-treated patients discontinued treatment due to a TEAE of dyskinesia and only 0.3% experienced dyskinesia as a serious TEAE. Other TEAEs included constipation, insomnia and dry mouth in opicapone- and placebo-treated patients, respectively.
Need to model aging in a hurry? Do it in outer space
What do you do when you’re studying age-related diseases but can’t wait around for tissue models to reach a ripe old age? You blast them into outer space, naturally.
It’s no secret that after traveling in space, astronauts’ bodies experience changes that resemble aging: bone loss, muscle deterioration and altered immune systems, to name a few. These result from prolonged exposure to microgravity, or gravity that is “diminished or close to zero gravity compared with Earth.” Scientists at the National Institutes of Health (NIH) and the International Space Station (ISS) are harnessing these age-accelerating effects to create models of various age-related diseases, a process that includes sending tissue models into space.
Tissue chips—also called tissue-on-a-chip or organ-on-a-chip—are tiny 3D models of human organ systems. Scientists use them to model diseases and test how drugs might affect specific organs. The NIH struck a deal this week with StemoniX to use its brain-on-a-chip technology in opioid research.
“Tissue chips in space provide a way to model various diseases of the aging process. Such models can be difficult or take a long time to develop here on earth but are greatly facilitated under microgravity, and scientists can use them to develop drugs that can prevent or slow down those diseases,” said Danilo Tagle, Ph.D., associate director for special initiatives at NIH’s National Center for Advancing Translational Sciences (NCATS), in a statement. “Taking this technology into space is an unprecedented opportunity to use tissue chips for accelerating translational development of interventions for use here on earth to treat many aging-related diseases.”
NCATS, the NIH’s National Institute of Biomedical Imaging and Engineering, along with the ISS U.S. National Laboratory, are supporting research under their Tissue Chips in Space program. The first set of chips—developed at the University of California, San Francisco to model the immune system—arrived at the ISS in December. A second shipment is due to blast off this weekend.
That set includes lung and bone marrow chips from the Children’s Hospital of Philadelphia and University of Pennsylvania, kidney chips from the University of Washington, bone and cartilage chips from MIT and chips modeling the blood-brain barrier from the biotech company Emulate. The hope is these projects will speed up the development of treatments for osteoarthritis, kidney stones and other conditions.
The team on the space station will infect the lung and bone marrow chip with Pseudomonas aeruginosa, a bacterium associated with hospital-acquired diseases, said Lucie Low, Ph.D., the scientific program manager for the NIH’s Tissue Chip for Drug Screening program.
“They will see how the bacterium affects lung tissues—because we know that the immune system changes up in space—and they will also be looking at how the bone marrow responds to that lung infection by the mobilization of neutrophils, which are white blood cells, in the bone marrow,” she said.
The cartilage and bone chips will be modeling post-traumatic osteoarthritis in the knee joint.
“They will be looking at a lot of different kinds of ‘omics’ outcomes from the tissues when they are up in microgravity: proteomics, metabolomics, different kinds of cellular, molecular and metabolic changes in tissues that result from microgravity,” Low said.
The kidney chip, meanwhile, will help with osteoarthritis research, as well as research into kidney stones.
“Astronauts seem to suffer from an increase in kidney stones and lose a lot of bone mass very rapidly when they enter microgravity,” she said. “Because the kidney filters a lot of blood, an increased calcium concentration leached from the bones in microgravity turns up in the kidneys in the form of kidney stones.
The tissue chips are slated to hitch a ride from Cape Canaveral, Florida, this weekend—as part of a payload of more than 5,400 pounds that includes crew supplies, hardware and other scientific experiments. The launch was postponed twice this week due to technical issues, and is now scheduled for the early morning hours of Saturday.
Clock is Ticking Faster for a Patient Turned Medical Disruptor
Onno Faber, a 36-year-old tech entrepreneur, stands straight up in the center of a modest living room, his shoeless feet planted in the gray striped rug. He looks trustingly at the music teacher who faces him, flashing her his frequent, accepting smile. Then he takes a breath, lifts his clear tenor voice, and sings.
Tomorrow, Onno will be video conferencing with parents of children who have rare diseases, to pitch them on his new tech platform to propel unconventional medical research. Today, he is far away from all that, as his voice reverberates through this little San Francisco room, lifting it up and away from the desperate streets of the Tenderloin neighborhood below. The notes vibrate in his wavy blond hair and green eyes, and in the tumor that’s growing quickly on his right hearing nerve — the only hearing nerve he has left. Onno is hearing the sound fill his body while he still can, before neurofibromatosis takes the other nerve away.
There comes a moment in any quest when it pivots from idea to reality. The blueprint is sketched, the parts are assembled, and someone hits the ignition — and with that, the idea is no longer in a safe, controlled space. Other people are watching now, influencing it, invested in it. The transition is equal parts exciting and scary. There is no turning back now.
Onno has hit that moment in two quests at once, one professional and one personal. Professionally, he is working apace to build an online application that will disrupt and accelerate the development of drugs for rare diseases. Personally, he is striving to use that same technology, along with his genetic data, to find a treatment that will prevent him from becoming deaf, blind, and unable to walk, before it’s too late.
Both efforts began a year ago, when 150 biologists and informaticians convened for a weekend hackathon in San Francisco to search Onno’s genetic data for clues to the cause of his tumors. (NEO.LIFE has been following the story since then; you can read the first episode here.)
Onno, a Netherlands native living in the Bay Area, had hatched the plan with his tech-industry friends. Their basic idea was to use powerful computer analytics on patients’ data to identify new treatments for their neglected diseases. Since then it has evolved into a fast-growing startup company that just raised $3 million in seed funding. It has registered 150 patients using its Web platform. And it’s collaborating with researchers at the National Cancer Institute to track pain symptoms in people with a type of neurofibromatosis called NF1. It is time for Onno’s idea to be tested.
The company, called RDMD, provides patients an online “locker” in which to store their entire medical record. Rather than wrestling with copious binders and CDs, chasing documents scattered across multiple hospitals and clinics, they can keep everything immediately accessible. They can easily share those records with rare-disease specialists, whom RDMD will help them find. And in time, they should be able to use RDMD to arrange for new medical tests.
RDMD is one of many emerging companies aiming to mine data for new insights about health and to personalize treatments for individual patients’ mutations. Yet it is distinguished by, among other features, its specificity. The platform launched with a setup devoted to Onno’s form of neurofibromatosis, NF2, which causes tumors to grow on the nerves that enable hearing and balance. For people with that diagnosis, RDMD’s platform tracks records such as hearing tests and radiology reports. Eventually, RDMD will scale up to serve patients with other rare diseases, as well, and the records it holds will be tailored to their needs.
By keeping specific data for each rare disease, on everything from drug responses to everyday symptoms, and by forging relationships with patients with those diagnoses, RDMD could make itself a one-stop partner for any pharmaceutical company that might research a treatment. Onno calls it “patient-accelerated drug development.”
One mother calls RDMD “exactly what we’ve needed.”
“If the data is not in the hands of the individual patients, it is not very easy to get access to it,” he says. Empowering patients to upload and house their own data is “going to liberate it, because patients, of course, want to contribute to whatever helps drive research forward.”
Already, around 15 patients have used RDMD to consult with a specialist located far from their homes. One father in Israel used it to consult with specialists in Los Angeles, Boston, and Paris before deciding whether to proceed with a risky surgery for his 10-year-old daughter, who has NF2.
And already, pharmaceutical companies have approached RDMD about tapping its data for research, says Onno’s cofounder, Nancy Yu, who previously led corporate development at 23andMe. Some, however, have wanted to do it the old way, treating the information as proprietary.
“We’ve already had partners who are willing to throw hundreds of thousands of dollars at us, but they want exclusive rights to that data, and we’re like: there’s no way,” she says. “We’re working for the patients first. … Especially in rare [diseases], you can’t afford to have these data silos. That’s been a thing of the past.”
Onno has personally promised patients that they will control their medical data. In May, he stood in front of several dozen patients, and parents of patients, at the Children’s Tumor Foundation NF Forum in Atlanta and told them that they will have the opportunity to opt their own records in or out of any study hosted on RDMD. In June, he promised a group called NF Moms Rock, via video conference, the same thing.
“You accept that responsibility by going out with it and presenting it to patients and raising the money,” Onno says. “That’s the moment when you are officially committing to the problem. … It’s just a point of no return.”
Onno is simultaneously making a watershed choice for himself: to try a drug that isn’t approved for NF2, in hopes of shrinking the tumor in his brain. In the same month this spring when he raised RDMD’s seed funding and got his green card to remain in the U.S., Onno received MRI results that confirmed the tumor had grown 35 percent in the past six months.
It was Onno’s quest for data that led him to decide on this new drug. A genome analysis that Onno had before last year’s hackathon showed that he had a mutation on chromosome 7 that could be contributing to his particular case of NF2. And there is a drug that can essentially patch that mutation. It’s called lapatinib, and it’s typically used to treat breast cancer. But it’s not approved by the Food and Drug Administration for NF2, so even though doctors can prescribe it, health insurers are not obliged to cover it.
The price tag for Onno’s prescription runs an estimated $10,000 a month.His doctors urged him to get the new MRIs to strengthen his case for insurance coverage, by showing that the tumor on his right hearing nerve was growing quickly. The MRI results have confirmed that fact, and his insurance finally will cover the drug. He expects to start taking it soon.
Onno marks the changes in his condition not by everyday increments, but by events, and the decision to try lapatinib is another milestone. “That makes this very real again,” he says. “Like: oh fuck, I might get these pills for the first time.”
Onno feels pretty much the same from day to day — except that he notices his balance getting a little worse, especially in the dark, on uneven pavement. Lapatinib will probably make him feel worse. Its side effects typically include nausea, vomiting, diarrhea, sleeplessness, and painful, peeling skin on the hands and feet. But he wants to try it while his tumor is still fairly small; it’s about a centimeter across. He wants to have time to try something else if lapatinib doesn’t work. It’s a logical choice, not an emotional one, he says: “It’s like a calculator, and you do what the calculator tells you.”
Whether lapatinib works for Onno is just as unknown as whether RDMD will thrive as a business.
Chris Garabedian, founder of the biopharma accelerator Xontogeny, who is not involved with RDMD, says a critical factor will be whether the startup offers a unique resource to the pharmaceutical industry. “We haven’t seen a lot of great examples of how companies have been able to monetize or create great value from just the collection even of comprehensive data sets,” he explains. To change that, RDMD needs to serve as a partner to drug companies in designing studies, building on deep and indispensable knowledge of each disease.
“If RDMD says, ‘We understand NF patients better than anybody. We have a database of them and real-time access to them. We have not only genetic information but natural history, drugs they’ve been on. We actually understand what endpoints you should be capturing in your clinical trial, and we can help you shape your clinical protocol,’ … that becomes probably the strongest value proposition that I’ve heard,” Garabedian says. To get there, he cautions, the company has to use its seed funding wisely, to land a significant research contract and demonstrate clear value before it needs its next infusion of money.
Onno and Nancy understand that RDMD has to deliver that kind of value. They say they’ve built the platform to comply with FDA regulations so that the data it holds can be used to measure the performance of drugs through clinical trials. They hope to provide patients access to tests and services that are hard for individuals to arrange, such as volumetric tumor studies—special analyses of high-resolution MRI scans that calculate the three-dimensional growth of a tumor over time. And RDMD is finalizing a contract with a lab that will sequence the genomes of RDMD users.
About 15 patients on the platform already have said they want the genome analysis and are prepared to pay the $2,000 cost. When that’s done, it will make it possible to do something that Onno has been pursuing for a year — to mine a bigger set of genomes for discoveries about the possible causes of NF2, building on the clues that emerged from his own genome at the first hackathon. He is planning a second hackathon for this fall.
“We have this opportunity to discover all of the things we don’t know yet,” he says.
Sheila Cohoon, a leader of the NF Moms Rock group who lives in Clinton Township, Michigan, calls RDMD “exactly what we’ve needed.” Her 9-year-old son, Nic, developed NF1 as an infant and suffers from its associated learning disabilities and low muscle tone. But Cohoon adds a warning for Onno as he develops this rich online resource: “He has to get the security to be bulletproof. Every day you’re hearing about how somebody’s hacked into this or security has broken on that. … People are still scared of it.”
Around the time of the first hackathon, and two years after getting diagnosed with NF2, Onno started taking singing lessons with teacher Emily Thebaut. Even as a child he wished he could sing, he says, but the pursuit seemed too “vulnerable.” Then he learned he had a disease that would probably make him deaf, on a timetable no one can predict. His first tumor took the hearing in his left ear. He figured he’d better start singing now.
There is so much going on now, in both Onno’s business and his illness, that when he talks the details spill out of his mouth as if he almost doesn’t know what to say first or next. “It’s good,” he says. But, for the first time since last summer’s hackathon, there’s a hint of hesitation in his voice.
“It’s like a calculator, and you do what the calculator tells you.”
Onno sets those concerns aside at his singing lesson, as Emily warms him up with scales. Near the bottom of his range, he giggles: “Sorry, nervous laugh.” She pushes him one note further.
With his right hand on his belly, he breathes deeply. Band-Aids wrap around four fingers on that hand, where he tore them up at the rock climbing gym the day before. His socks, a festival of multicolored polka-dots, actually match today, unlike usual.
Onno sings with the same openness and eagerness to learn that he brings to genomics and biotech business, laughing with each error that leads to a lesson. Emily has urged him to sing publicly, but he’s not in this to perform. He practices songs while walking the streets of San Francisco. Sometimes he gets quieter when someone passes, sometimes he brushes aside self-consciousness and carries on. He likes when that happens.
“When it works there is a mode of not thinking,” he says about singing. “It’s very liberating, very free, like you don’t care about anything, you’re just getting it out there.”
Free the voice, free the spirit, free the data.
Emily completes the warmup, and it’s time for Onno to choose a song. He calls up the lyrics on a digital tablet, holds it aloft, and sings:
“In your dreams, whatever they be,
dream a little dream of me.”
dream a little dream of me.”
American Society of Gene & Cell Therapy Meeting: Highlights
The annual meeting of the American Society of Gene & Cell Therapy (ASGCT) was held in Washington, DC last week, with literally hundreds of abstracts and presentations. Here’s a look at some of the highlights.
Children with X-linked MTM Breathe on Their Own after Gene Therapy
Researchers with Audentes Therapeutics, Hopital Armand Trousseau in Paris, UCLA Medical Center, Children’s Hospital of Chicago and several other institutions, presented data from a Phase I/II clinical trial of gene therapy in X-linked Myotubular Myopathy (XLMTM). XLMTM is a rare monogenic disease caused by mutations in the MTM1 gene, which codes for myotubularin, which is a protein needed for development and function of skeletal muscle. The disease results in extreme muscle weakness, respiratory failure and early death. Of the nine boys who received the gene therapy, all have improved neuromuscular function, most can sit on their own and four can now breathe on their own without ventilators. Principal investigator Perry Shieh, a neurologist at UCLA, said the boys “have gone from nothing to something. Time will tell how much that something will be.”
The gene therapy is AT132, which delivers functional copies of the MTM1 gene to skeletal muscle cells.
MaxCyte Presented Data on CARMA Trial in Cancer
Gaithersburg, Md.-based MaxCyte presented data on its CARMA drug candidate, MCY-M11, a mesothelin-targeting chimeric antigen receptor (CAR), which is in a Phase I clinical trial in mesothelin-expression solid tumors at the National Cancer Institute (NCI) and Washington University in St. Louis.
The CARMA platform is noted for its rapid manufacturing and delivery capabilities without a viral component, which was also a significant aspect of the presentation. “The advancement of our first CARMA clinical trial, which is consistently showing the feasibility of our rapid manufacturing process, is significant for MaxCyte and the application of our technology,” stated Claudio Dansky Ullmann, MaxCyte’s chief medical officer. “Development of a cell therapy with application in solid tumors is impactful for patients with unmet needs in a variety of cancers and we look forward to further advancing this program.”
Moderna Presented Research from 7 mRNA-based Therapies, and 5 Oral Presentations
Moderna always has a lot of irons in the fire and they presented research on many of them at the meeting. The data included preclinical research in ornithine transcarbamylase deficiency (OTC) in collaboration with the Perelman School of Medicine at the University of Pennsylvania; maple syrup urine disease (MSUD), also in collaboration with Penn; arginase-1 (ARG1) deficiency in collaboration with the University of California, Los Angeles Department of Surgery and Department of Molecular and Medical Pharmacology; Factor VIII deficiency (hemophilia A), in collaboration with Seattle Children’s Research Institute; and several other programs.
“mRNA medicines have the potential to treat the underlying cause of many metabolic diseases, and may offer important advantages over conventional gene and enzyme replacement therapies for eligible patients,” stated James M. Wilson, director of the Gene Therapy Program at Penn. “This includes the potential to develop controlled, dose-dependent and transient treatments that may benefit infants and children with these disorders and patients with diseases that are not addressable with current viral-based approaches.”
Translate Bio Presented mRNA Therapies in Metabolic Disorders
Translate Bio presented “Treatment of Metabolic Disorders Using Lipid Nanoparticle (LNP)-Encapsulated Messenger RNA Therapeutics (MRT).” The presentation summarized data from research in three mouse models of metabolic disorders including ornithine transcarbamylase (OTC) deficiency, arginosuccinate synthetase (ASS1) deficiency (citrullinemia) and methylmalonic acidemia (MMA).
“We have engineered our mRNA therapeutic (MRT) platform to deliver mRNA that codes for the missing enzymes in several metabolic disorders,” stated Frank DeRosa, Translate Bio’s senior vice president of research and process development. “These data demonstrate the potential broad applicability of the MRT platform to treat various genetic disorders using our proprietary liver delivery technology.”
Homology Medicines Discusses Gene Therapy Platform
Homology Medicines discussed its manufacturing platform, including serum-free suspension transfection, which is both scalable and optimized to manufacture its adeno-associated virus vectors (AAVHSCs). Specifically, its AAVHSC15 vector showed an 18-fold decrease in phenylalanine compared to an AAV5 vector carrying the identical DNA construct in the phenylketonuria (PKU) murine model.
“We have a great sense of urgency to advance our gene therapy and gene editing programs with the goal of bringing transformative treatments and potential cures to patients with rare genetic diseases,” stated Albert Seymour, Homology’s chief scientific officer. “We are pleased to share the progress that we have made across our PKU and MLD development programs, as well as demonstrate the scalability, quality and superiority of our manufacturing process for our human-derived AAVHSCs. We are carrying this momentum forward in our IND-enabling studies in MLD and in our gene editing program for PKU and look forward to starting our Phase I/II pheNIX trial in adults with PKU and reporting initial clinical data this year.”
Neurocrine, Voyager Parkinson’s Phase 1 at American Academy of Neurology
- Results Confirm the Posterior Trajectory as an Additional Surgical Delivery Route for VY-AADC in Patients with Parkinson’s Disease
- Treatment with VY-AADC Improved Good ON Time (ON Time Without Troublesome Dyskinesia) by 1.7 Hours and Reduced OFF Time by 2.2 Hours at 12 Months in Patients with Parkinson’s Disease
Neurocrine Biosciences, Inc. (NASDAQ: NBIX) and Voyager Therapeutics, Inc. (NASDAQ: VYGR) today announced Phase I trial results for VY-AADC from eight patients with Parkinson’s disease who participated in the open-label trial to evaluate the safety and efficacy of VY-AADC and to further assess the posterior (i.e., from the back of the head) surgical delivery approach. These Phase I results are being presented today as a poster presentation at the 2019 American Academy of Neurology (AAN) Annual Meeting. Parkinson’s disease is a chronic, progressive and debilitating neurodegenerative disorder that affects approximately one million people in the U.S.1
Treatment with VY-AADC improved good ON time (ON time without troublesome dyskinesia) by 1.7 hours from baseline and reduced OFF time by 2.2 hours at 12 months from baseline in patients with Parkinson’s disease. Exploratory analyses in four of the eight patients with low or no dyskinesia or absence of impulse control disorder (ICD) at baseline demonstrated a greater improvement in motor function including a 3.2-hour improvement in good ON time from baseline to 12 months. Infusions of VY-AADC were well tolerated with no serious adverse events (SAEs) reported. These Phase I results show that the posterior trajectory is an additional surgical delivery route in patients with Parkinson’s disease.
“The results from this Phase I trial in patients with Parkinson’s disease provide further evidence that VY-AADC administration can allow neurons in the brain to convert levodopa to dopamine and improve motor function,” said Eiry Roberts, M.D., Chief Medical Officer at Neurocrine Biosciences. “The results from this trial confirm previous data from a separate, ongoing Phase I study demonstrating that increased coverage of the putamen with VY-AADC leads to an increase in AADC enzyme activity and improvements in motor function and quality of life in patients with Parkinson’s disease – with less need for oral levodopa medication.”
AUA’19: Clinical guidance for radiation therapy after prostatectomy
The American Society for Radiation Oncology (ASTRO) and the American Urological Association (AUA) today announced updates to their joint clinical guideline on adjuvant and salvage radiotherapy after prostatectomy in patients with and without evidence of prostate cancer recurrence to include new published research related to adjuvant radiotherapy.
The Adjuvant and Salvage Radiotherapy after Prostatectomy: ASTRO/AUA Guideline (available online in the Journal of Urologyand in Practical Radiation Oncology was amended as follows:
- Guideline Statement 2 was modified to account for the latest data from three randomized controlled trials evaluating the use of adjuvant radiotherapy, including new long-term data from the ARO 96-02 trial, which was incorporated to update the existing evidence base.
- Statement 2: Patients with adverse pathologic findings including seminal vesicle invasion, positive surgical margins, and extraprostatic extension should be informed that adjuvant radiotherapy, compared to radical prostatectomy only, reduces the risk of biochemical (PSA) recurrence, local recurrence, and clinical progression of cancer. They should also be informed that the impact of adjuvant radiotherapy on subsequent metastases and overall survival is less clear; one of three randomized controlled trials addressing these outcomes indicated a benefit, but the other two trials did not demonstrate a benefit. However, these two trials were not designed to identify a significant reduction in metastasis or death with adjuvant radiotherapy.
- Guideline Statement 9 is a new guideline statement written to include outcome data from two randomized controlled trials (RTOG 9601 and GETUG-AFU 16), which evaluate the effects of hormonal therapy on overall survival, and on biochemical and clinical progression among patients who received salvage radiotherapy after prostatectomy. Based on findings from these randomized controlled trials, it was concluded there was sufficiently strong evidence overall to encourage hormonal therapy to be offered to patients who are candidates for salvage radiotherapy. When offered, the clinician must provide information about benefits and harms associated with this therapy, particularly discussing the improved freedom from disease progression documented in both trials, and improved overall survival as reported in RTOG 9601.
- Statement 9: Clinicians should offer hormonal therapy with radiotherapy to patients who are candidates for salvage radiation therapy. Ongoing research may someday allow personalized selection of hormonal or other therapies within patient subsets.
In addition to the guideline statements, new information related to genomic classifiers, as predictors of treatment effectiveness, was added to the guideline future research needs. Further study in this area is needed to determine whether a genomic classifier is predictive of outcomes in a yet to be treated patient, and whether it is predictive for efficacy of a particular treatment.
“Evidence from three, well-established randomized trials now confirm significant improvements in biochemical recurrence-free survival among patients with adverse pathological features with the use of adjuvant radiotherapy,” said Ian Thompson, MD, co-chair of the guideline panel and professor and chairman of the urology division at the University of Texas Health Sciences Center at San Antonio, Texas. “Our expectation is this guideline is fully aligned to the latest science and provides physicians with a relevant blueprint for the use of radiotherapy after prostatectomy.”
“As research in prostate cancer evolves and improves, data continue to accumulate in support of radiotherapy following radical prostatectomy. We now know that radiotherapy and the combination of hormone therapy with radiation, following radical prostatectomy, have contributed to even more favorable outcomes for patients than seen previously,” said Richard K. Valicenti, MD, FASTRO, co-chair of the guideline panel and professor and chairman of radiation oncology at the University of California-Davis Comprehensive Cancer Center in Sacramento, California. “With the current update, this collaborative guideline now reflects nearly three decades of multidisciplinary research.”
Story Source:
Materials provided by American Society for Radiation Oncology. Note: Content may be edited for style and length.
Journal Reference:
- Thomas M. Pisansky, Ian M. Thompson, Richard K. Valicenti, Anthony V. D’Amico, Shalini Selvarajah. Adjuvant and Salvage Radiotherapy After Prostatectomy:ASTRO/AUA Guideline Amendment Executive Summary 2018. Practical Radiation Oncology, 2019; DOI: 10.1016/j.prro.2019.04.008
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