Details of the VISION trial of Lu-177... - Advanced Prostate...

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Details of the VISION trial of Lu-177-PSMA-617 presented at ASCO

Tall_Allen profile image
Tall_Allen

(I wasn't sure if the link would work for everyone, so here's the whole press release)

ASCO 2021: VISION Shows Addition of 177Lutetium-Labeled Prostate-Specific Membrane Antigen Improves Outcomes in Advanced Prostate Cancer

Pending regulatory approval, this could become a novel treatment approach

June 6, 2021—177Lutetium-labeled prostate-specific membrane antigen (PSMA) resulted in improvements in both progression-free survival (PFS) and overall survival (OS) when given in combination with standard of care in patients with metastatic castration-resistant prostate cancer (CRPC), according to results of the VISION trial, presented at the annual meeting of the American Society of Clinical Oncology, which took place online from June 4 to 8.

“Prostate cancer is the most common cancer in American men and the second leading cause of cancer-related death,” said lead author Michael J. Morris, MD, of Memorial Sloan Kettering Cancer Center in New York City, during a press conference attended by Elsevier’s PracticeUpdate. “Metastatic CRPC is the terminal phase of this disease and has a limited number of effective and durable treatment options. PSMA is an enzyme that is highly expressed on the surface of prostate cancer [cells] across the disease spectrum and across disease sites. Expression on normal tissue is limited, making PSMA an excellent target for both PET imaging and targeted systemic radiation treatment, which is known as radioligand therapy. PSMA-617 targets PSMA with high affinity and delivers a payload of 177lutetium, a beta particle emitting radioactive metal.” Upon uptake of the molecule, the prostate cell is exposed to a lethal dose of radiation and subsequently dies.

The VISION trial was designed to evaluate the efficacy and safety of 177lutetium-labeled PSMA-617 to standard of care in patients with advanced prostate cancer. For the international, open-label, phase III trial, 831 patients with PSMA-positive metastatic CRPC were randomized 2:1 to either 200 mCi of 177lutetium-PSMA-617 for 4 cycles every 6 weeks plus standard of care (n = 551) or standard of care alone (n = 280). All patients had received previous treatment with at least 1 androgen receptor inhibitor and 1 or 2 chemotherapy regimens. “Only patients for whom chemotherapy was felt to be inappropriate were eligible,” said Dr. Morris.

Standard of care was planned before randomization and excluded chemotherapy, immunotherapy, radium-233, and investigational drugs. Responders with residual disease could receive combination treatment for 2 extra cycles. The alternate primary endpoints were radiographic PFS and OS. If either or both of these endpoints were positive, the trial was considered a success.

Treatment with 177lutetium-labeled PSMA resulted in a 38% reduction in risk of death, compared with standard of care alone (95% confidence interval 0.52–0.74, P < .001) and a prolonged median OS (15.3 months vs 11.3 months). A 60% reduction in risk of radiographic progression was also found in the combination arm (95% confidence interval 0.29–0.57), as well as improvement in radiographic PFS, with a median of 8.7 months in the combination arm versus 3.4 months with standard of care alone.

Side effects were more common in the combination arm, with 23.4% experiencing high grade (3–5) bone marrow suppression versus 6.8% of patients treated with standard of care alone. Common side effects of any grade included fatigue (49.1% vs 29.3%), dry mouth (39.3% vs 1.0%), and nausea/vomiting (39.3% vs 17.1%).

“The VISION study demonstrated that patients with metastatic CRPC, who have already progressed after both androgen receptor pathway inhibitors and chemotherapy, had significantly improved OS and radiographic PFS if they received 177lutetium-PSMA in addition to safely combinable standards of care, relative to those standards alone,” concluded Dr. Morris. “These findings do warrant adoption of 177lutetium-PSMA as a new treatment option in this patient population, pending FDA review. There are ongoing studies of patients with prostate cancer at earlier phases of the disease using this agent.”

“This trial shows an alternative to traditional therapies by using radiation targeted to PSMA, so it can be delivered directly to the prostate cancer cells. By doing that, survival was significantly improved,” said Lori J. Pierce, MD, of the University of Michigan in Ann Arbor, at the ASCO press conference. Dr. Pierce spoke in her capacity as ASCO president. “Use of this PSMA radioligand therapy, if it obtains regulatory approval, could indeed become an important treatment option in [these patients].”

practiceupdate.com/c/cc7fa2...

32 Replies

Thank you Allen!

Thanks for posting!

Thank you again Allen!

Good information, Allen. Thank you.

Thanks a lot, TA. we do appreciate your efforts always.

You make life easier!!!....Your dedication to all fighting this disease gives us a clearer picture to engage an effective battle plan!!!....!!THANKS!!

Thanks . Wonder how AC-225 may improve results further?

Tall_Allen profile image
Tall_Allen in reply to lewicki

The side effects are worse, we know that much so far.

You always seem to be here for us TA. Thank you for all the long hours. Much appreciation!

Thanks for posting! Can you please explain what a 38% reduction in the risk of death actually means? I assume it's over some unstated time scale, otherwise it would imply that 38% of patients gain immortality.

While the results are good, the local news has been mentioning the trial results as "game changing", which I think is very misleading. They kept the story short, and avoided interviewing the patient with the best, most miraculous response as if everyone did that well on the drug. No mention was made of the 4 month increase in median survival. Just wanted to vent about how the news covers these studies, which make friends and relatives tell me about this great new breakthrough that will have me cured any day now.

Anomalous profile image
Anomalous in reply to tom67inMA

Fake news

Tall_Allen profile image
Tall_Allen in reply to tom67inMA

It means that within the timeframe of follow-up, 38% fewer men died if they got Lu-177-PSMA than the men who got SOC. I agree that most popular media don't cover any medical stories well.

monte1111 profile image
monte1111 in reply to tom67inMA

I was also informed that I was cured by this "new" breakthrough. Who knows? Maybe I will be. A few may win the cancer lotto. (I think most of us agree it will be a combination of treatments and that there is no silver bullet. I'm keeping my Lone Ranger costume handy, just in case.)

tom67inMA profile image
tom67inMA in reply to monte1111

I'm just about convinced that any trial of appreciable size produces several miracle results, including a few from the control group that never get any press coverage. After all, last year;s breakthrough medicine is today's control group.

lewicki profile image
lewicki in reply to monte1111

hi monte1111. What was your treatment?Thanks

monte1111 profile image
monte1111 in reply to lewicki

Sorry. Wrote a bad sentence. I have not had a "new" treatment as that may have implied. Just same ole Lupron, Chemo, and Xtandi, etc. I guess you can call them fairly new in the scheme of things. SOC has worked very well. The Xtandi ride must someday end. And then things will get interesting.

why not use this therapy for all apc cases

Seems this may become standard therapy

I do not know if this therapy has been used in Germany since long...

In Israel Australia India..

any comments...

Tall_Allen profile image
Tall_Allen in reply to Karmaji

They are starting trials in France for earlier use.

Karmaji profile image
Karmaji in reply to Tall_Allen

Thanks.....My onco last week was very excited....I did not catch well his remark mixed it with scan...

clinicaltrials.gov/ct2/show... you previously mentioned this trial for hormone sensitive in US. I included here so people can look if relevant to them.

Gods info. Thank-you

Only in France and Spain so far

Thanks. Missed that.

Thank you Tall Allen. My husband was in the trial and it extended his life. He experienced minimal side effects. He enjoyed exercise and activities with friends and family, returned to work part time and was a loving husband and father. The work of Tall Allen and others in the Prostate Cancer community gave him hope and reliable facts. He lived a good life. We lost him 11 weeks ago and miss him deeply. Everyday I am grateful for my darling man and thankful that this cancer is so well understood. You have made the world a better place by your good work. You are cherished.

Tall_Allen profile image
Tall_Allen in reply to AAhealth

I am so sorry to hear this. I know sometimes I hear about innovations in cancer therapy for cancers my parents or friends died of and wonder if they could have lived longer. It is frustrating but also encouraging that maybe someone else will not have to endure what they went through. I hold onto the perspective that we are all in this together across time and space.

I’m wondering how strong the radioactivity of 177Lutetium-PSMA is. Compared to normal scans or X-rays.

As an insulin pump user with Hormone resistant advanced PC, I cannot expose my Medtronic insulin pump nor continuous glucose monitor (CGM) to radiation, fluoroscopy, X-rays, scans etc. it will damage my pump.

Is 177-Lutetium very low level radiation compared to X-rays?

Lu-177 mostly emits a different type of radiation - beta particles, not X-rays. Unlike X-rays, beta particles don't penetrate very far through tissue. Lu-177 also emits some gamma rays of low energy. The PET scan they use emits positrons and it is used together with a CT (X-ray) scan. Check with the manufacturer of your device.

Reviewed the information including Dr. Morris' presentation at ASCO. Nice to have the positive results out. But am concerned about the very high rate of bone marrow suppression, in approximately 1/4 of patients. What I could not find in the presentation was the proportion of patients who had Gr 3 or greater bone marrow suppression broken down by those who had PSMA bone mets vs. those who had only lymph node and/or visceral PSMA avid sites. Seems important and likely that this would occur in those with more PSMA lesions in bones.

About 10% had liver metastases. IDK how many had non-pelvic LN metastases (M1a). . Patients with super-scans were excluded and they had requirements for adequate bone marrow function. They didn't allow chemo or Xofigo as part of the SOC because they were concerned about bone marrow function.

Actually interested in how those with bone marrow suppression correlated with bone metastasis. Would those with no avid bone mets be at much lower risk for serious bone marrow suppression? Seems a natural question. Thanks.

I would guess that almost all the patients had at least some bone metastases. Of course those with no bone metastases would have no bone marrow suppression - the PSMA radiopharmaceutical only attaches to sites that express PSMA. If those sites are not in the bones, they could not suppress bone marrow.

Thank you for posting this. In a month or two MaleCare will sponsor a one hour summary of ASCO 2021 geared towards patients. I enjoy those summaries very much.

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