Nubeqa (darolutamide) reduces risk of death and delays onset of chemo in nmCRPC

Nubeqa (darolutamide) reduces risk of death and delays onset of chemo in nmCRPC

Darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) led to a 31% reduction in the risk of death compared with placebo and ADT in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), according to results of the final overall survival (OS) analysis of the phase III ARAMIS trial, which were presented during the 2020 ASCO Virtual Scientific Program.

At the primary analysis, the median metastasis-free survival (MFS) was 40.4 months with darolutamide versus 18.4 months with placebo, leading to a 59% reduction in the risk of metastasis or death.  Darolutamide had also demonstrated a favorable safety profile, with no increased incidence of most adverse events (AEs) that are associated with the agent, at this time point.

Results also showed that darolutamide significantly delayed time to pain progression, with a median 40.3 months versus 25.4 months with placebo.  Nubeqa also delayed the time to first cytotoxic chemotherapy.  Dr. Fizazi, however, did note that cardiac arrhythmias, including those of grade 3/4 in severity, were higher with darolutamide (7.3% and 1.8%, respectively) than with placebo (4.3% and 0.7%).

You can read the full news release from CURE here: http://tiny.cc/Nubeqa-darolutamide

Nubeqa (darolutamide) reduces risk of death and delays onset of chemo in nmCRPC

Lutetium PSMA-617 more active than Jevtana in mCRPC Phase 2 trial

Results from the TheraP Phase 2 trial found that in men with metastatic castration resistant prostate cancer who progressed after treatment with docetaxel, 177Lu-PSMA-617 was more active than cabazitaxel (Jevtana), according to data presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

The data also demonstrated that grade 3 or 4 side effects, which are considered serious or severe, were less common in patients who received LuPSMA.  PSA-progression-free survival (PSA-PFS) favored LuPSMA as well.  The randomized phase II trial included men with mCRPC post docetaxel suitable for cabazitaxel, progressive disease with rising PSA and PSA ≥ 20 ng/mL.  Prior to admission to the trial, Imaging with PSMA radiotracers had to confirm that the patients’ tumors had high PSMA-expression to be eligible.

The PSA response rate was higher in patients who received LuPSMA than those who received cabazitaxel (66% vs 37%; P< 0.001). This represented a 29%, (P< 0.0001) absolute greater PSA response rate in participants receiving LuPSMA compared to cabazitaxel.

You can read the full news release here: http://tiny.cc/CURE-News-LuPSMA

Nubeqa (darolutamide) reduces risk of death and delays onset of chemo in nmCRPC

Hi-Risk/Recurrent/Advanced PCa Men & Caregivers Recording – June 9, 2020

Editor’s Pick: Why are there no new chemotherapy treatments for prostate cancer?

Topics Discussed

Using Procrit; docitaxel + carboplatin study; chemotherapy issues; bone density scans; itchy skin; cramping; chemo cycles vs rounds; pre-chemo advice; why no new chemo treatments?;genetic vs somatic gene testing; Covid19 impact on advanced treatment; scanning for recurrence – sensitivity; ROS1 mutation; liquid vs solid Bx analysis; are metastatic PCa cells homogenous; rectal pain post RT

Chat Log

AnCan Barniskis Room (to Everyone): 3:23 PM: https://www.auajournals.org/doi/10.1097/JU.0000000000000971.017

Len (to Everyone): 4:25 PM: Germline mutations are inherited. Somatic mutations are specific to the tumor cells only.

AnCan Barniskis Room (to Everyone): 4:55 PM: https://www.fredhutch.org/en/news/center-news/2016/02/metastatic-prostate-cancer-and-precision-oncology.html

Ken Anderson: 4:57 PM: MDA thinks the bone mets have different structure then one another

AnCan Barniskis Room (to Everyone): 5:01 PM: Journal study ….. http://www.eurekalert.org/pub_releases/2016-02/fhcr-poc022516.php

More Evidence to add Palliative Care Early!

More Evidence to add Palliative Care Early!

Here is more evidence to support AnCan’s position that it is benficial to add palliative care to your medical team early for those diagnosed with T3/T4/advanced cancer.

While we question the validity of the statistical results based on the large drop-out rate that likely selects for lower overall survival, there is no question in our minds that palliative care is very helpful in manging treatment symptoms and side effects.

Onward & upwards …. rd

 

Participants in Early-Phase Clinical Trials Need Better Palliative Care Integration

Patients participating in phase 1 clinical trials could benefit from the integration of palliative care, according to data presented at the 2020 ASCO Virtual Scientific Meeting.
BY BRIELLE BENYON
PUBLISHED JUNE 05, 2020

Palliative care is an integral part of a cancer treatment plan and should not be dismissed for patients who are participating in clinical trials. In fact, data presented at the 2020 ASCO Virtual Scientific Meeting showed that patients participating in phase 1 clinical trials tended to have improved quality of life (QOL) outcomes when they received palliative care.

“We all know that ASCO now recommends concurrent palliative care by a palliative care team within eight weeks of diagnosis based on multiple randomized trials showing improved symptoms, improved quality of life, less depression and anxiety, despite increased prognostic awareness,” Dr. Thomas J. Smith, professor of oncology at Johns Hopkins Medicine, said during a pre-recorded presentation of the research.

A total of 209 patients at Johns Hopkins Sidney Kimmel Cancer Center and City of Hope received a palliative care intervention, which included two nurse-led visits to discuss physical, psychological, social, and spiritual issues, as well as advance directives. There was then an interdisciplinary team meeting to discuss each patient and make recommendations. There was also a single goals of care (GOC) discussion.

These patients were then compared to the control arm, consisting of 218 patients. However, by the end of the study, there were 112 patients who completed the intervention arm and 113 patients in the control arm. Others either withdrew or refused, were too ill to complete the study, died, or were lost to follow-up.

“In fact, the mean overall survival was 8.1 months. So that fits appropriately with palliative care and advanced medical directives,” Smith said.

The initial distress thermometer score was 3.6, “where most authorities recommend that 3 is a cutoff for an intervention,” according to Smith.

Patients provided with palliative care showed less psychological distress (average score of 1.9 in the intervention arm, vs. 1.2 in control). Though not statistically significant, the palliative care group also had a trend toward improved QOL (3.7 vs. 1.6).

Participants had high rates of symptom-management admissions (41.3%) and low rates of advance directive completion (39%). A total of 30.7% of patients used supportive care services, including hospice. There was no clinically significant change in patient satisfaction with oncology care providers, which was already high at baseline.

Ultimately, the researchers concluded that there is a need for better integration of palliative care for patients participating in phase 1 clinical trials, especially as patients move from treatment to supportive care at the end of their lives.

“Remember to always ask about symptoms and advanced medical directives, even in phase I patients because they will have symptoms,” Smith said. “And most of them want to have a discussion with (oncologists) about advanced medical directives.”

Living as a Rare Disease Patient and Advocate During COVID-19 and The Protests

Living as a Rare Disease Patient and Advocate During COVID-19 and The Protests

The ‘superstar’ lead moderator for our Sarcoidosis Virtual Support Group, Frank Rivera, contracted Covid19 and came close to death. Wth his lungs already significantly compromised by sarcoidosis, Frank made the strategic decsion to stay at home in Huntington, Long Island rather than enter a New York area hospital.

It paid off … read his blog post that appeared on Arianna Huffington’s Thrive Global blog today! Frank is back to running  our 3 monthly virtual groups! And it appears AnCan is keeping him sane – as he says:

One thing that has helped me is having our Sarcoidosis (Virtual) Online Support Group Meeting. That has been a Godsend to me. It has helped not just everyone else,but me very much so.

What a partnership! Read Frank’s blog post and background here.

O&U rd

 

Nubeqa (darolutamide) reduces risk of death and delays onset of chemo in nmCRPC

Hi-Risk/Recurrent/Advanced PCa Men & Caregivers Recording – June 1, 2020

Editor’s Pick: PRINT trial examines small cell/NE morphing … not to mention EXERCISE beats fatigue! (rd)

Topics Discussed

DeNovo Metastatic man enters trial for HPN424; yet more monotherapy bicalutamide – after 17 yrs of no treatment!; FMI finds ROS1 – what next; introducing palliative care; bone cancer pain or arthritis; PRINT trial looks to thwart PCa cells morphing to small cell/NE; clinical trials still shut down nationally; to radiate or not with 5 lesions?; Procrit?; another denovo Mx man asks should he do chemo?; EXERCISE WORKS to relieve fatigue from salvage RT!!!; remedies for hot sweats.

Chat Log

Jake (to Everyone): 5:19 PM: HPN424

Jake (to Everyone): 5:20 PM: https://www.biospace.com/article/releases/harpoon-therapeutics-announces-preliminary-safety-and-pharmacology-data-from-its-hpn424-phase-1-trial-in-prostate-cancer/

Rich Jackson (to Organizer(s) Only): 6:22 PM: About rhPSMA rhPSMA-7.3 (18F) consists of a radiohybrid Prostate-Specific Membrane Antigen (PSMA)-targeted receptor ligand which attaches to and is internalized by prostate cancer cells, and is labeled with the 18F radioisotope for PET imaging. Single intravenous administration of rhPSMA-7.3 (18F) for PET Scan

Dennis Correia (to Everyone): 6:32 PM: nct#02903160 (PRINT Trial)

Larry Fish (to Everyone): 7:05 PM: MMR mismatch repair deficiency

AnCan – Rick (to Everyone): 7:15 PM: https://www.urotoday.com/video-lectures/mcrpc-treatment/video/mediaitem/843-embedded-media2017-10-09-16-50-00.html?utm_source=newsletter_4869&utm_medium=email&utm_campaign=navigating-the-course-of-treatment-new-findings-meet-old-habits-findings-from-latitude

Nubeqa (darolutamide) reduces risk of death and delays onset of chemo in nmCRPC

Hi-Risk/Recurrent/Advanced PCa Men & Caregivers Recording – May 26, 2020

 

Pick of the Week …. long term monotherapy bicalutamide (Casodex)

Topic discussed

Mayo Clinic & Medicare reimbursement; PSMA scans vs starting ADT and salvage radiation on recurrence; USPSTF PSA recommndations result in advanced Dx and death; long-term monotherapy bicalutamide (Casodex); olaparib & CDK12; diet during salvage RT; novel abiraterone protocol; intervention after surgery; compassionate vs off label use; drug pricing after FDA approval; Richard Foody RIP

Chat Log

Peter Kafka : 3:41 PM: DR. Felix Feng at UCSF rad onc is amonst the best in the nation. Hard to get to him. He came from Michigan and is well known for his research in prostate cancer.

AnCan – Rick (to Peter Kafka): 3:55 PM: You are right – forgot about Felix. Best to let Borno direct him ….

Richard Stanton (to Everyone): 4:02 PM: Anyone who wants to chat offline please contact me. Thanks. (Ed. If you wish to discuss bicalutamide monotherapy, please contact info@ancan.org for Richard Stanton’s email address)

Nubeqa (darolutamide) reduces risk of death and delays onset of chemo in nmCRPC

USPSTF’s PSA recommendations prove criminal!

Not before time, researchers are looking closely at the impact of the USPSTF advisories to stop (2012) or limit (2016) PSA screening. Back in the day, PCa advocates submitted our comments warning exactly of the morbid findings you can read below. It ain’t brain surgery to work out that:

“These data illustrate the trade-off between higher screening rates and more early-stage disease diagnoses (possibly overdiagnosis and overtreatment) and lower screening rates and more late-stage (possibly fatal) disease,”

Problem was, there were no brain surgeons on the USPSTF Panel in 2012… neither were there any urologists if my memory serves me right,. The Chair was a pediatrician!

These stats upset the PCa advocay community greatly. We are the ones working with younger men, often with kids in their tweens and teens, who wonder if they will see them graduate high school, never mind college. Some of you know that AnCan (https://ancan.org) suports a virtual group specifically for men under 60 with advanced PCa in respnse to the need we have identified.

What good does “We told you so” do as we see PCa specific deaths mount. What USPSTF did was criminal – it has resulted in a significant uptick in PCa specific deaths estimated by ACS as increasing 25% in number over the past 4 years. If nothing more, USPSTF should apologize and take responsibility. They were forewarned!

 

Advanced Prostate Cancer Cases Continue to Rise in U.S.

— Lasting effect of USPSTF’s 2012 recommendation against PSA testing

Coinciding with declines in prostate-specific antigen (PSA) screening over the last decade, the incidence of intermediate- and high-risk prostate cancer has continued to increase across the U.S. in men 50 and older, a nationwide, population-based analysis has shown.

From 2008 to 2012, ahead of the United States Preventive Services Task Force (USPSTF) recommendations against PSA testing for prostate cancer, incidence of distant-stage disease was increasing by 2.4% per year for men 50 to 74 years. But this more than doubled to 5.6% per year from 2012 to 2015, reported Ahmedin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, and colleagues.

Their analysis in the Journal of the National Cancer Institute also found that in men 75 and older, incidence of distant-stage prostate cancer increased by 5.2% per year from 2010 and 2016.

In contrast, incidence of local-stage disease decreased by 6.4% per year in men 50 to 74, from 2007 to 2016. And in men 75 and older, declined by 10.7% per year from 2007 to 2013, and then stabilized.

From 2009 to 2016, the researchers estimated that 11,387 more men were diagnosed with distant disease than would have been diagnosed had the incidence rates remained at their 2008 nadir. But 633,111 additional local cancers would have been diagnosed from 2008 to 2016, had rates for local disease remained at their 2007 peak.

“These data illustrate the trade-off between higher screening rates and more early-stage disease diagnoses (possibly overdiagnosis and overtreatment) and lower screening rates and more late-stage (possibly fatal) disease,” the investigators wrote. “The persistently increasing regional- and distant-stage prostate cancer incidence during the past 5 years has public health implications given the substantial morbidity and premature mortality associated with it.”

Starting about 5 years ago, investigators including Daniel Barocas, MD, MPH, of Vanderbilt University in Nashville, began documenting a decline in the incidence of localized prostate cancer and hinted at a rise in the incidence of non-localized disease in the wake of the 2012 USPSTF recommendations against PSA-based screening.

“The study by Jemal et al actually quantifies the trade-offs associated with this policy,” Barocas told MedPage Today. By 2016, localized cases — representing a combination of “overdiagnosed” low-risk cases and higher-risk localized cases that are destined to progress — had declined by over 115,000 per year.

At the same time, “non-localized (lethal) cases had increased by over 3,500,” Barocas wrote in an email. Although the USPSTF updated the recommendations for PSA screening in 2018, suggesting that decision-making for PSA-based screening should be “individualized” for men ages 55 to 69, “decoupling” the diagnosis of localized disease and treatment did not seem to reduce the survival benefit associated with screening, he added.

Furthermore, “urologists, all reputable guideline bodies, and increasingly the public, have embraced the concept of observing low-risk prostate cancer. And continued efforts to improve the specificity of screening and to increase the use of observation for low-risk disease will preserve the survival benefit and reduce metastatic disease associated with screening while minimizing the harms associated with overdiagnosis,” Barocas continued.

For the new study, all prostate cancer cases diagnosed from 2005 to 2016 were obtained from the U.S. Cancer Statistics 2001 to 2016 Public Use Research Database, which covers 100% of the U.S. population. Men were stratified by disease stage, age, and race/ethnicity.

Incidence of local-stage disease in men 50 and over increased from 456.4 to 506.1 per 100,000 from 2005 to 2007, and then plummeted to 279.2 per 100,000 by 2016, Jemal and co-authors reported.

In contrast, incidence of regional-stage disease generally increased across the same study interval, from 5.7 to to 9.0 per 100,000 men from 2005 to 2016. For distant-stage disease, incidence rates declined from 23.1 to 22.4 per 100,000 from 2005 to 2008, but then increased to 29.7 per 100,000 men by 2016.

“For all races/ethnicities combined, the incidence patterns for age 50-74 and ≥75 years are generally similar to those of age ≥50 years, with the incidence rates after the late 2000s declining for local-stage disease but increasing for regional- and distant-stage disease” — the one exception being for men 75 years of age and older, among whom the incidence of local-stage disease stabilized from 2013 to 2016, Jemal and co-authors noted.

Jemal and co-authors also noted a “substantial decline” in the racial disparity in the incidence of distant disease in black and white men age 50 to 74. But this coincided with a steeper increase in the incidence of distant disease in non-Hispanic white men over the study period, and the incidence of distant disease in non-Hispanic black men still remains two to three times higher than in non-Hispanic white men among those under 75, and is 65% higher in men 75 and older, the researchers noted.

“The harms associated with high PSA screening rates can be mitigated while preserving the benefit of screening through PSA-stratified strategies including longer screening interval based on baseline PSA, higher PSA threshold for biopsy referral in older men, and restricting routine testing to men age ≤70 years,” the team wrote. “And future studies are needed to elucidate the reasons for the rising incidence trends for regional- and distant-stage disease and for the disproportionately high burden of the disease in black men.”

Asked for his perspective, Thomas Ahlering, MD, of the University of California (UC) Irvine, noted that he and his colleagues have documented a similar pattern of prostate cancer incidence rates as an unintended consequence of decreased PSA-based prostate cancer screening. In a 2018 study, the team found that the proportion of low-grade prostate cancers decreased significantly from a pre-recommendation average of 30.2% in 2012 to an average of 17.1% in 2016.

In contrast, the incidence of high-grade cancers with Gleason scores of 8 and over increased from a pre-recommendation low of 8.34% to a post-recommendation high of 13.5%. There was also a 24% increase in absolute numbers of Gleason 8 and above cancers in the post-recommendation interval.

“The major difference between this study and our own is that their study is clinical and ours was pathological, meaning it used a surgical database,” Ahlering told MedPage Today. “We were picking up much more regional disease with metastatic potential.”

This regional disease — which can be thought of as intermediate risk, he said — is much more burdensome for patients and especially for the healthcare system, because it usually necessitates some form of secondary intervention. And that secondary intervention likely costs about the same as the first intervention cost — i.e., around $40,000 per year.

Linda Huynh, MSc, also of UC Irvine, noted that research from Ruth Etzioni and colleagues has shown that if PSA screening were continued, but only for men younger than 70, more than half of avoidable cancer deaths could be prevented, while at the same time the strategy would dramatically reduce overdiagnoses compared with continued PSA screening for all ages.

“Etzioni has said, and we applaud it: ‘Discontinued screening for all men eliminated 100% of overdiagnoses but failed to prevent 100% of avoidable cancer deaths,'” Huynh said. “So it really is a matter of systematically screening first, and then you can worry about overtreatment and complications from treatment after the cancer is diagnosed.”

Ahlering also noted that screening recommendations may be “tinkered” with as much as anyone might like, but what is really needed are centers of excellence where prostate cancer is expertly treated: “The initial intervention for a man with prostate cancer needs to last 22 years or more,” he said. “So how a patient gets treated is as important or more important than anything else — that is what we are pushing for at least — you just can’t pull the plug and stop doing PSA screening.”

Disclosures

The study was funded by the American Cancer Society (ACS), and the authors, ACS employees, noted the ACS receives grants from private and corporate foundations, including foundations associated with companies in the health sector for research outside of the study, and that the authors are not funded by any of these grants and their salary is solely funded through ACS funds.

Neither Ahlering nor Huynh had any conflicts of interest to declare

Barocas disclosed relevant relationships with Astellas, MDxHealth, Janssen, and Tolmar.

Nubeqa (darolutamide) reduces risk of death and delays onset of chemo in nmCRPC

Lynparza (olaparib) is now FDA-approved for Advanced Prostate Cancer

Following closely on the heels of the very recent FDA approval of Rubraca (rucaparib) for advanced prostate cancer in men with a BRCA1/2 mutation, we now have a second PARP-inhibitor approved by the FDA.  This one has the trade name of Lynparza and generic name of olaparib.  This approval was based on the recently published Phase 3 clinical trial in the New England Journal of Medicine.  Whereas Rubraca was approved for men who previously failed both chemotherapy and a second line antiandrogen (such as Zytiga, Xtandi, Erleada, etc.), Lynparza is approved even if the patient hasn’t had any chemotherapy.

You can read the full PCF press release here: https://www.pcf.org/blog/breaking-news-fda-approves-olaparib-for-treatment-of-advanced-prostate-cancer/

Nubeqa (darolutamide) reduces risk of death and delays onset of chemo in nmCRPC

Hi-Risk/Recurrent/Advanced PCa Men & Caregivers Recording – May 18, 2020

Editor’s Pick – Low PSA with high volume metastasis (rd) + successful treatment for ‘young’ man with de novo metastatic disease

Topics Discussed

de novo Mx with low PSA; clinical trial conflicts; biopsy sample from primary vs. Mx tumor; relevance of bone density tests; young de novo Mx man finds successful treatment; debulking the primary; when the end may not be the end!; bone biopsies; testing for PSMA avidity; PSMA scan availability in Covid times; testosterone swings; shipping delays for abiraterone; specialty pharmacies; what is the ‘doughnut’ hole?; abscopal/immuno effect from RT

Chat Log

scott (to Everyone): 5:05 PM: is this link the same link for all meetings?

Ken Anderson (to Everyone): 5:06 PM: scott yes this is the same meeting room

scott (to Everyone): 5:07 PM: 100 degrees isn’t fun…

Dell Jensen (to Everyone): 5:38 PM: Both Lupron and Docataxel

Dell Jensen (to Everyone): 5:43 PM: Rick is correct, treating the primary is critical

scott (to Everyone): 5:48 PM: is docetaxyl an infusion or a pill?

Dell Jensen (to Everyone): 5:48 PM: infusion

Ken Anderson (to Everyone): 5:49 PM: infusion once every three weeks

scott (to Everyone): 5:49 PM: do you do docetaxyl if the Zytiga I am on isn’t working?”

Ken Anderson (to Everyone): 5:49 PM: you can for sure do both at the same time…

scott (to Everyone): 5:51 PM: does the docetaxil have hard side effects?

Dell Jensen (to Everyone): 5:51 PM: osteoporosis is a result of ADT treatment

Dell Jensen (to Everyone): 5:51 PM: I definitely concur

Dell Jensen (to Everyone): 5:52 PM: my side effects were minimal, infections were my problems.

Ken Anderson (to Everyone): 5:52 PM: all chemo has side effects.. doce has some for sure and all are post on the web.

scott (to Everyone): 5:53 PM: thanks ken

Peter Kafka (to Everyone): 5:54 PM: I had a specialized genetic test from MIRA labs that gave me a risk assessment for developing a grade 2 or greater adverse reaction to PD1/PDL1 agent therapy.

Russ Smith (to Everyone): 6:28 PM: Good night all. It’s been a long day.

scott (to Everyone): 6:31 PM: is david muslin head of answer cancer foundation?

Len (to Everyone): 6:35 PM: No, Rick is head of AnCan

scott (to Everyone): 6:36 PM: I sent a donation to ancan fdn in honor of rick and have heard nothing

Len (to Everyone): 6:36 PM: It will be acknowledged soon, if in fact they received it properly.

scott (to Everyone): 6:37 PM: thanks…just want to make sure rick is honored by donation

scott (to Everyone): 6:39 PM: is speaking freely 8 pm az time?

Rich Jackson (to Everyone): 6:43 PM: Speaking Freely starts at 8pm EST.

scott (to Everyone): 6:43 PM: thanks

Rich Jackson (to Everyone): 6:43 PM: Same connection as this call.

scott (to Everyone): 6:53 PM: who is the gentleman now speaking?

Dell Jensen (to Everyone): 6:53 PM: Correia

Dell Jensen (to Everyone): 6:55 PM: Are there other compounding pharmacy?

Dell Jensen (to Everyone): 6:57 PM: I have local one that is in Rock Island, IL