Certain Toxic Effects Higher With New... - Fight Prostate Ca...

Fight Prostate Cancer

2,898 members1,132 posts

Certain Toxic Effects Higher With Newer PCa Therapies— Reviews suggests increased risks of cognitive adverse events, fatigue, falls

cujoe profile image
5 Replies

No time to thoroughly read and write this one up, but wanted to get it out for review and comment.

Certain Toxic Effects Higher With Newer Prostate Cancer Therapies - Systematic reviews suggests increased risks of cognitive adverse events, fatigue, falls - by Mike Bassett, Staff Writer, MedPage Today May 26, 2023

Second-generation anti-androgens (AAs) for the treatment of prostate cancer are associated with an increased risk of cognitive and functional toxic effects, according to results from a systematic review and meta-analysis.

Across 12 randomized trials involving over 13,000 patients, increased risks of cognitive toxic effects (risk ratio [RR] 2.10, 95% CI 1.30-3.38, P=0.002) and fatigue (RR 1.34, 95% CI 1.16-1.54, P<0.001) were observed in patients treated with second-generation AAs compared with those in control arms, reported Kevin T. Nead, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues.

The findings were consistent when the analysis was limited to studies that included traditional hormone therapy in both treatment arms for cognitive toxic effects (RR 1.77, 95% CI 1.12-2.79, P=0.01) and fatigue (RR 1.32, 95% CI 1.10-1.58, P=0.003), they noted in JAMA Oncology.

They also found that a greater median age was associated with a greater risk of fatigue with second-generation AAs (coefficient 0.75, 95% CI 0.04-0.12, P<0.001).

In addition, the use of AAs was associated with increased falls (RR 1.87, 95% CI 1.27-2.75, P=0.001). The observed increased risk of falls -- which included those that required hospitalizations and invasive interventions -- "indicates the importance of counseling patients on fall risk and implementing preventive measures as appropriate," Nead and team said.

"To our knowledge, these results are the first to suggest an association between second-generation AAs and cognitive and functional toxic effects based on data from prospective RCTs [randomized clinical trials]," the authors wrote. "Our work supports the need for further research to determine how to identify, prevent, and treat cognitive and functional toxic effects in patients treated with second-generation AAs."

Nead and team said their findings have important implications for patient care.

"Because use of second-generation AAs is becoming more prevalent in prostate cancer treatment, there is an increasing need to identify and treat individuals experiencing adverse cognitive effects," they noted, adding that timely interventions for these patients should be feasible since they have regular healthcare exposures.

In a commentary accompanying the study,opens in a new tab or window Alexandra O. Sokolova, MD, and Julie N. Graff, MD, both of the Knight Cancer Institute at Oregon Health & Science University in Portland, agreed that the results suggest clinicians should carefully consider the risks and benefits when prescribing these therapies for individual patients.

"Ultimately, the goal of prostate cancer treatment is to improve patients' quality of life while minimizing the risk of adverse outcomes, and this study provides valuable information to help achieve that goal," they wrote.

Currently, there are four second-generation AAs approved by the FDA for metastatic hormone-sensitive prostate cancer: abiraterone (Zytiga), enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). While these agents have improved patient survival, Nead and colleagues noted that retrospective evidence suggests there is an association between these drugs and adverse cognitive and functional outcomes. However, they added, "further data from prospective trials are needed."

Their systematic review and meta-analysis included 12 studies comprising 13,524 patients, all of which were multinational with data collection that occurred between 2008 and 2021.

All participants had metastatic and nonmetastatic prostate cancer at enrollment, with a median age across studies of 67 to 74 in both the intervention and control arms. Study follow-up time ranged from 3.9 to 48 months.

Nead and colleagues acknowledged several limitations to their study. For example, they used tabular summary count data that didn't account for time to event. Therefore, they reasoned that if second-generation AAs resulted in increased survival, that could bias the results since patients treated with AAs are more likely to be alive and experience toxic effects.

"Regardless, the large magnitude of increased risk combined with the large absolute number of toxic effects reported suggest that these toxic effects are important to consider when counseling and managing treatment in this group of patients," they wrote.

MedPage article is here:

Certain Toxic Effects Higher With Newer Prostate Cancer Therapies - Systematic reviews suggests increased risks of cognitive adverse events, fatigue, falls - by Mike Bassett, Staff Writer, MedPage Today May 26, 2023

medpagetoday.com/hematology...

and the JAMA Oncology paper is here:

Association of Second-generation Antiandrogens With Cognitive and Functional Toxic Effects in Randomized Clinical TrialsA Systematic Review and Meta-analysis, JAMA Oncology, Original Investigation, May 25, 2023

jamanetwork.com/journals/ja...

Stay S&W, Ciao - K9

Written by
cujoe profile image
cujoe
To view profiles and participate in discussions please or .
Read more about...
5 Replies
MateoBeach profile image
MateoBeach

Very important information to consider in the risk vs reward consideration of adding advanced ARSI drugs (or however we are calling the group ). I could not get the full text behind the JAMA paywall. (Really JAMA?) I am curious if they could break out the estimated average risks for each agent.

Scout4answers profile image
Scout4answers

Very thought provoking

castration = no drugs AND that was my choice and I'm sticking with it 👍👍

NPfisherman profile image
NPfisherman

K9 Terror,

I do wonder how intermittent therapy may decrease those toxic SEs from ARPI therapy (like Pablo said...what are we calling them now??). I call for a head to head study to compare continuous vs intermittent tx in regards to these SEs. It will happen some day.

Hope all is well with you. Can't wait to come home on Sunday from Fla.

DD

cesces profile image
cesces

This sort of makes intuitive sense to me.

Most of these treatments are sort of abusive generally. That's why they work.

They are wearing on other parts of your body, so why not your brain.

Not what you're looking for?

You may also like...

FDA Grants Priority Review to Olaparib for HRR-Mutant mCRPC - Targeted Oncology - January 20, 2020

The FDA has granted a Priority Review to the New Drug Application for olaparib (Lynparza) as...
cujoe profile image

EMBARK Study: Enzalutamide +/- ADT

Results of the EMBARK study was published this week (10/19/23) in NEJM. It compared high risk BCR...

Revisiting the ORIOLE trial--SBRT vs Observation--Key Take Home points for the Oligometastatic PCa patient

Hello FPC members, After exchanging messages with another member, I wanted to review again the...
NPfisherman profile image

Reducing the side-effects of prostate hormone therapy with exercise - New report from the other side of the pond

We all know and are constantly reminded that exercise is key to combating the side effects of ADT....
cujoe profile image

Anyone on Nubeqa ? on triplicate therapy, Firmagon, Zytiga & Prednisone Started Docetaxel Chemotherapy no mention of Nubeqa DX 07/2022

currently doing docetaxel had second infusion on 09/13/22 suffers from plaque psoriasis  Nubeqa...