Price to Pay for Intermittent ADT in Advanced Prostate Cancer

[JimJimJimJim]

Jim Marshall (not a doctor) said ...

For the men in this study:

• Continuous hormone treatment (ADT) was better overall than intermittent ADT (5.8 years vs. 5.1 years). The study was designed to answer this question, so your doctor can consider this evidence strong. It was statistically significant.
  
• Looking at the data after the study, it seems:
  
  • Men with minimal metastatic disease (no spread beyond the the spine, pelvis, and lymph nodes) did much better on continuous ADT (7.1 years vs. 5.2 years).
    
  • Men with more extensive disease spread (to the ribs, long bones, and/or liver and lungs) survival was similar in both continuous and intermittent groups.
    
  • As the study had not been designed to answer these questions, your doctor will consider this evidence less strong.
    

Not all men with metastatic disease were included in this study. The men in this study had to start with a PSA of at least 5, and have that PSA fall below 4 after 7 months ADT. They also had to be not too sick (a performance status of 0-2 – if they had to spend more than half the day in a chair or bed, they were not eligible). (If you don't know how the performance status works, see our topic (which also refers to a Wikipedia entry on performance status):

Performance status

There's more highlighting by me (not at doctor) in the following article below from Medscape.com than I have ever used before, so, if you intend talking to your doctor about this, there is a lot to attend to.

... end Jim

'Price to Pay' for Intermittent ADT in Advanced Prostate Cancer

Nick Mulcahy

June 3, 2012 (Chicago, Illinois) — The intermittent use of androgen-deprivation therapy (ADT) in men with metastatic prostate cancer is inferior to continuous ADT in terms of survival, according to the results of a landmark international phase 3 trial.

"Continuous therapy continues to be the standard of care" in men with metastatic disease that is hormone sensitive,said lead author Maha Hussain, MD, from the University of Michigan in Ann Arbor.

She discussed study results from the Southwest Oncology Group (SWOG) 9346 trial at a press conference here at the 2012 Annual Meeting of the American Society of Clinical Oncology®. The full results will be presented at the meeting's plenary session.

For the study's primary outcome of overall survival, the researchers found that the 765 men treated with continuous therapy lived an average of 5.8 years, whereas the 770 men treated intermittently lived an average 5.1 years, said Dr. Hussain.

These outcomes translated into a 9% increase in the relative risk for death with the intermittent approach (hazard ratio,1.09; 95% confidence interval, 0.95 to 1.24).

This finding about intermittent therapy goes against "conventional belief," said Dr. Hussain. She was referring to the fact that many clinicians and academics have believed, on the basis of earlier research, that intermittent therapy could prolong disease response or was at least not detrimental in terms of survival, she said.

The impetus for using intermittent ADT has been to relieve men of the adverse effects of low testosterone, such as impotence and diminished well being, said Dr. Hussain

However, this study indicates that "there is a price to pay" for using ADT intermittently, said news briefing moderator Bruce J. Roth, MD, from the Washington University School of Medicine in St. Louis, Missouri.

The study results are "disappointing but make "intuitive sense," said Elizabeth Plimack, MD, from the Fox Chase Cancer Center in Philadelphia, Pennsylvania, who was not involved in the study.

She explained that "continuous androgen-deprivation therapy is the first-line standard of care for men with metastatic disease" to minimize tumor exposure to testosterone, which fuels prostate cancer, and to control disease progression.

Intermittent ADT is used in certain circumstances in men with metastatic disease, Dr. Plimack said.

"Intermittent ADT is sometimes used for men with minimal disease burden, low PSA [prostate-specific antigen], and significant side effects to LHRH agonists. Currently, this is done on a case-by-case basis, without the benefit of high-level evidence to support it,"she told Medscape Medical News.

Dr. Plimack pointed out that another major clinical trial has compared intermittent and continuous ADT in men with prostate cancer — but it was in men with localized disease who had PSA progression after radiation treatment. The trial, known as SWOG JPR 7, gave some credibility to the notion that intermittent therapy might not be costly to men in terms of survival.

The SWOG JPR 7 trial, reported at the 2011 Genitourinary Cancers Symposium, found that intermittent therapy was noninferior to continuous therapy with respect to overall survival.

Nonetheless, clinicians worry about suspending the therapy. " The concern is that an interruption in ADT could lead to disease progression, symptoms, and a decrease in overall survival."

With these new results for metastatic disease, the "balance has tilted" said Dr. Plimack. "Disease control becomes more important than protecting against the side effects of ADT" in the type of patients involved in the study.

Only Applies to This Type of ADT

One of the study's researchers cautioned that the results only apply to men who are treated in a manner similar to the study protocol.

"We cannot draw any conclusions about the myriad other androgen-deprivation regimens," Celestia Higano, MD, from the Seattle Cancer Care Alliance and the University of Washington, told Medscape Medical News about the study, which is a collaboration of the SWOG, the Eastern Cooperative Oncology Group, the European Organisation for Research and Treatment of Cancer, and the National Cancer Institute of Canada.

The study design called for all men to undergo a 7-month induction course of "combined" ADT (subcutaneous goserelin once a month and oral bicalutamide once daily for 8 courses).

Men whose PSA levels decreased to 4 ng/mL or less after months 6 and 7 of induction treatment, and who had a stable or declining trend, were deemed hormone sensitive and randomly assigned to either intermittent or continuous ADT for the duration of the trial. Men on intermittent therapy had their treatment initially discontinued and were monitored with PSA tests monthly; they resumed ADT if there values exceeded prespecified levels, Dr. Hussain explained.

Overall, the men in the study were "good actors"; they had responsive disease and thus were preselected, Dr. Hussain noted. This explains how the overall survival in the study was much better than is typically seen in men with metastatic disease, who typically only survive 2.5 to 3.0 years.

Patients whose PSA levels did not decrease to 4 ng/mL or less at the end of the induction phase of the trial were removed from the protocol and were simply observed for progression and survival.

Men in the study had metastatic stage IV prostate cancer and a minimum pretreatment PSA level of 5 ng/mL. Any number of bone metastases was allowed, as were metastases to the liver, brain, or lung. However, the men had to have a SWOG performance status score of 0 to 2.

To participate in the trial, the men had to be systemic treatment-naïve, although exceptions were made for men who were more than 1 year removed from any previous neoadjuvant or adjuvant hormonal therapy (a duration of no more than 4 months) and any previous finasteride treatment (a duration of no more than 9 months).

Intermittent Might Be Best for Extensive Disease

The intermittent approach to disease control achieved some of its desired effects, said Dr. Hussain at the press conference. After only 3 months of treatment, impotence, libido, and emotional functioning were all significantly better with intermittent than with continuous ADT. There was also a trend for improvement in physical functioning, she added.

An interesting subgroup analysis looked at the men in the study by the extent of their disease spread.

In men with more extensive disease spread (to the ribs, long bones, and/or liver and lungs), median overall survival was similar in the continuous and intermittent groups (4.4 vs 5.0 years).

However, the same analysis showed that intermittent ADT appears to be hazardous in men with minimal metastatic disease (no spread beyond the the spine, pelvis, and lymph nodes).

In such men, median overall survival was 5.2 years for those treated with intermittent therapy and 7.1 years for those treated with continuous therapy.

Both Dr. Hussain and Dr. Higano cautioned against putting much stock in these findings because they come from subgroup analyses.

However, they both suggested that clinicians discuss the findings with patients. Dr. Higano said that the decision on how to proceed with ADT in an individual patient is complex. "It has to come down to educating patients about the risks and benefits," she said.

Dr. Hussain reports receiving research funding from Abbott Laboratories, Astellas Pharma, Merck Serono, Millennium, NCCN, and Pfizer. Some of her coauthors report financial relationships, as outlined in the abstract. Dr. Plimack has disclosed no relevant financial relationships.

2012 Annual Meeting of the American Society of Clinical Oncology® (ASCO): Abstract 4. To be presented June 3, 2012.

Medscape Medical News © 2012 WebMD, LLC

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Snuffy Myers unimpressed by SWOG 9346.

Mis-match phase II and clinical observations are headscratchers, and more.

Video:

http://askdrmyers.wordpress.com/2012/06/13/continuous-v-iht-for-pca/