Chemotherapy-naïve (never had chemo) patients also deserve Zytiga “free” on the PBS
Prostate cancer (PC) is the most common male cancer in
Why is this group of cancer sufferers forced to endure the pain of advancing metastatic cancer in the bones, brain and liver before they are allowed to receive abiraterone funded by the PBS? When chemotherapy fails (and this is inevitable) they will be much closer to death and only then might the PBS pay for the medication. Why should they be denied a significant extension of life pain-free when this new drug Abiraterone can achieve this?
Already, there is excellent evidence that abiraterone can delay progression of the cancer, minimize symptoms and lengthen life.¹ ² Surely, Australian men with incurable prostate cancer are just as worthy of receiving costly treatment as others, eg, HIV aids, renal dialysis, organ transplants, etc.. The cost of chemotherapy and “best supportive care” treatment, alternatives to abiraterone that are already approved for subsidy for PC patients, can themselves be very expensive. Therefore the current restrictions on the availability of abiraterone are unreasonable and oppressive. Budgetary restrictions need to be lifted, otherwise many more men will die before they can get this new drug
STOP PRESS 08Feb'12: Extracts from Updated Research and Reports
It may take several months to receive Ministerial and Cabinet approval, which could still be denied. Even if a PBS subsidy is approved, it will benefit only those patients with incurable prostate cancer who have failed treatment with chemotherapy. Those who have not had chemo first will not be eligible. Unlike the FDA in the USA, The Therapeutics Goods Administration (TGA) in Australia has not given approval for these patients. Without such approval no application for PBAC consideration is possible under the "rules". As a consequence about 2,000 Australian men will inevitably develop painful secondaries forcing them onto chemotherapy. They are being left without access to this effective treatment that offers a pain-free extension of life. If the Government so decided, this process could and should be expedited)
from: National
Cancer Institute UPDATE of December 11, 2012 Report: "FDA
Approval for Abiraterone Acetate" (See WEB:
http://www.cancer.gov/cancertopics/druginfo/fda-abirateroneacetate )
URL abbreviated to: http://goo.gl/i3PBi
EXTRACT "
... abiraterone acetate was approved by the FDA* on December 10, 2012 for
the treatment of mCRPC patients prior to receiving chemotherapy."
* Food and Drug Administration - Reference: ¹Charles J. Ryan, et al. (for the COU-AA-302 Investigators). "Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy." N Engl J Med. 2013; 368:138-48 doi: 10.1056/NEJMoa1209096 (report updated
________________________________________________________________________________
from N Engl J Med. 2013; 368:138-48 (UPDATE 17Jan13) : "Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy" (See WEB: http://www.nejm.org/doi/full/10.1056/NEJMoa1209096 ) URL abbreviated to: http://goo.gl/39YeM
EXTRACT "Conclusions: Abiraterone
improved radiographic progression-free survival, showed a trend toward improved
overall survival, and significantly delayed clinical decline and initiation of
chemotherapy in patients with metastatic castration-resistant prostate
cancer."
_______________________________________________________________________________
from: UroToday (Urology
News) published on Friday, 08 February 2013 16:19 (referring to the above): "Abiraterone in metastatic prostate
cancer without previous chemotherapy (from study COU-AA-302)"
(See WEB: http://www.urotoday.com/Treatment-of-mCRPC/abiraterone-in-metastatic-prostate-cancer-without-previous-chemotherapy-from-cou-aa-302.html
) URL abbreviated to: http://goo.gl/D2NGm
EXTRACT "
... In summary, this shows that the patients can live longer without disease
progression, can live longer without symptoms, can live longer until
performance status deteriorates, can live longer until receiving chemotherapy,
can live longer until starting opiates for pain, and probably live longer
overall. ..."
_____________________________________________________________________________
My Goal: Make Abiraterone acetate (Zytiga)
available immediately via the Pharmaceutical Benefits Scheme for ALL patients
who have metastatic castration-resistant prostate cancer, without the current
requirement for prior treatment with chemotherapy.
Footnotes and References:
° Australian Institute of Health and Welfare (AIHW):
Cancer in Australia 2010: in brief. ISSN 1039-3307; ISBN 978-1-74249-081-6;
Cat. no. CAN 55; 28pp.
¹
American Society of Clinical
Oncology (ASCO):
ASCO Daily News
J Clin Oncol 30, 2012 (suppl; abstr LBA4518) “Interim analysis (IA) results of
COU-AA-302, a randomized, phase III study of abiraterone acetate (AA) in
chemotherapy-naive patients (pts) with metastatic castration-resistant prostate
cancer (mCRPC)” URL:
EXTRACTS of KEY POINTS:
“ … In patients with asymptomatic or mildly symptomatic chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate (AA) plus prednisone produced a statistically significant benefit in radiographic progression-free survival (rPFS) over placebo plus prednisone, according to a planned interim analysis of a phase III study. … “
“ …AA plus prednisone delayed disease progression,
increased survival, and extended time with minimal or no symptoms, said Charles
J. Ryan, MD, of the Helen Diller Family Comprehensive Cancer Center at the
University of California, San Francisco. In addition, no important new safety
signals were seen in the randomized, multicenter COU-AA- 302 study, added Dr.
Ryan,
“ …the co-primary endpoints of overall
survival (OS) and rPFS and secondary endpoints all favored the AA arm and
unanimously recommended unblinding the study and crossing patients over from
placebo to AA treatment, Dr. Ryan said.
“ …the objectives of therapy development in
this disease state have been met, … “
“ … These data merit consideration as
providing a new standard approach in this highly prevalent patient population
faced with an unmet medical need.”
“…
However, a reality is that much of the life of a patient with mCRPC is lived
before chemotherapy, and in fact a large proportion of patients never receive
it,” he said.
"The natural history of progressive mCRPC
can be prolonged, and can appear over a period of years. Therefore, several
hallmarks of disease progression (time to opiate use as a surrogate for
cancer-related pain, time to initiation of chemotherapy, time to Eastern
Cooperative Oncology Group performance status deterioration, time to PSA
progression) were used as secondary endpoints, to provide “a comprehensive
assessment of the magnitude of the clinical benefit conferred by AA,” Dr. Ryan
said. “Therapy with AA delayed, to a clinically significant degree, the onset of
these meaningful events,” he said. … “
http://www.nejm.org/doi/full/10.1056/NEJMoa1014618#t=abstract
² OncologyStat (a subscriber medical journal scanning and news
service)
“Abiraterone Delays Progression in
Patients with Chemotherapy-Naïve CRPC,” ASCO 2012: Conference
Coverage Roundup: Abstract from: IMNG Medical Media. 2012 Jun 11, P Wendling
“Abiraterone Blocks Chemo-Naïve Prostate Cancer”
(Note: to read the full article it is necessary to sign up to this professional cancer news publication, OncologyStat; it takes only a few seconds on this URL and membership is free).
EXTRACTS of KEY POINTS:
“CHICAGO (EGMN) - Abiraterone acetate plus prednisone significantly delays progression and initiation of chemotherapy in asymptomatic or mildly symptomatic, chemotherapy-naive, metastatic, castration-resistant prostate cancer, according to much-anticipated data from a pivotal clinical trial. >
The second preplanned interim analysis of the COU-AA-302 trial also revealed a strong overall survival trend favoring abiraterone (Zytiga) over prednisone and placebo, leading to unblinding of the phase III trial in March 2012 and crossover treatment for the control arm. … “
“… This is the first trial to show progression and overall survival benefits in this setting. Janssen Research & Development announced it will seek a new indication for abiraterone in chemotherapy-naive, metastatic, castration-resistant prostate cancer (mCRPC) in the second half of 2012. >
The combination of abiraterone plus prednisone has already demonstrated an overall survival benefit in patients with prior chemotherapy, leading to its approval in April 2011 for mCRPC that had previously been treated with docetaxel (Taxotere) chemotherapy.…”
(author’s
note: From the expert commentaries extracted above two compelling reasons
emerge as to why a PBS subsidy should apply without further delay for chemo-naïve
mCRPC patients. One derives from the evidence that abiraterone is effective and
“safer …” and this has been acknowledged by the PBAC (plus Janssen-Cilag is
seeking FDA approval in the USA for this group on the same basis).
The other is that the strength of this evidence led the COU-AA-302 clinical trial to be unblinded early so as to permit the
control group to receive the obvious benefits of the drug. Their lives would
otherwise have been sacrificed, arguably unjustifiably in order to keep the trial
“pure”. This is the moral and ethical dilemma that can sometimes arise and it
serves as a timely reminder that real people are affected for better or worse
by decisions made in the name of scientific purity. Other trials are also
ongoing in the USA to confirm
the safety of abiraterone. The outcomes will be very important. Nevertheless,
there is already sufficient evidence in its favour to permit eligible patients
to make an informed decision on the balance of risks to benefits of receiving
this drug now instead of chemotherapy. It should be their choice.)
³ Pharmaceutical Benefits Advisory Committee (PBAC)
EXTRACTS of KEY MILESTONES:
Nov, 2011 Pharmaceutical Benefits Advisory Committee (PBAC) Public Summary Document
http://www.health.gov.au/internet/main/publishing.nsf/Content/pbac-psd-abirateronee-nov11
“… 2. Background
The Rule of Rescue:
There are four factors which when applied concurrently in exceptional circumstances, are called the ‘rule of rescue’ as follows.
- No alternative
exists in Australia to treat patients with the specific circumstances of the medical
condition meeting the criteria of the restriction. This means that there
are no nonpharmacological or pharmacological interventions for these
patients.
- The medical condition defined by the requested
restriction is severe, progressive and expected to lead to premature
death. The more severe the condition, or the younger the age at which a
person with the condition might die, or the closer a person with the condition is to death, the more
influential the rule of rescue might be in the consideration by PBAC.
- The medical condition defined by the requested
restriction applies to only a very
small number of patients. Again, the fewer the patients, the more
influential the rule of rescue might be in the consideration by PBAC.
However, PBAC is also mindful that
the PBS is a community-based scheme and cannot cater for individual
circumstances.
- The proposed drug provides a worthwhile clinical
improvement sufficient to qualify as a rescue from the medical condition.
The greater the rescue, the more influential the rule of rescue might be
in the consideration by PBAC.
(author’s note: the italics are mine)
“ … 11. Estimated PBS Usage and Financial Implications
The net financial cost to the PBS was estimated by the submission to be between $30 – $60 million in Year 5 of listing. The estimate was considered uncertain because of the potential of extended use beyond disease progression given the safety profile and ease of administration of abiraterone.”
“ … 12. Recommendations and Reasons … ”
“ … Whilst the PBAC considered that there are uncertainties inherent from indirect comparisons, it accepted the submission’s clinical claims: … 3) abiraterone plus prednisone/prednisolone is non-inferior in terms of comparative effectiveness and superior in terms of comparative safety over cabazitaxel plus prednisone/prednisolone alone. … ”
(author’s note: this assertion stands in contradistinction to those in the key points in reference¹ above, in particular, “ … AA plus prednisone delayed disease progression, increased survival, and extended time with minimal or no symptoms” … and “…“Therapy with AA delayed, to a clinically significant degree, the onset of these meaningful events, … ” ie, Abiraterone is better than non-inferior. It is acknowledged by the PBAC as safer.)
“ … The PBAC therefore rejected the submission on the basis of an unacceptably high incremental cost-effectiveness ratio and due to uncertainty regarding the clinical place in therapy.”
“ … 14. Sponsor’s Comment
The sponsor has no comment.“
(author’s note: in reference ² above, third key point, see: “ … Janssen Research & Development (USA) announced it will seek a new indication (ie, FDA approval) for abiraterone in chemotherapy-naive, metastatic, castration-resistant prostate cancer (mCRPC) in the second half of 2012. … “ In view of this more recent announcement by the sponsor’s
March 2012 PBAC Outcomes - Positive Recommendations:
http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/pbac-outcomes/2012-03/positive-recommendations
“PBS Listing requested by the sponsor (Janssen-Cilag Pty Ltd):
Authority Required listing for the initial and continuing treatment, in combination with prednisone or prednisolone, of patients with metastatic advanced prostate cancer (castration resistant prostate cancer) in whom disease progression has occurred following treatment with docetaxel”
“PBAC Recommendation:
Recommended on a cost-minimisation
basis with cabazitaxel. The PBAC noted that abiraterone has a better safety
profile and is more convenient to administer (oral administration) than
cabazitaxel.”
(author’s notes:
a) “cost-minimization” !
b) in reference ² above, third key point, see: “ … Janssen Research & Development announced it will seek a new indication for abiraterone in chemotherapy-naive, metastatic, castration-resistant prostate cancer (mCRPC) in the second half of 2012. … “ but this is in the
Janssen
July 2012 Agenda for the July 2012 PBAC Meeting
http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/pbac-agenda
“Re-submission to request a review of the March 2012 PBAC recommendation for an Authority Required listing for the initial and continuing treatment, in combination with prednisone or prednisolone, of patients with metastatic advanced prostate cancer (castration resistant prostate cancer) in whom disease progression has occurred following treatment with docetaxel.”
(author’s note: It is still not being considered for “chemotherapy-naïve”patients (those who have not yet had chemotherapy) even though they also have advanced cancer and are incurable. The “excluded ” group are still being left to get worse and condemned to chemotherapy.)
26 Sep12 Agenda for the November 2012 PBAC Meeting
“Resubmission
ABIRATERONE,
tablet, 250 mg (as acetate), Zytiga®
Prostate
cancer
Requests a review of the PBAC’s March 2012 recommendation to list abiraterone on a cost‑minimisation basis to cabazitaxel as an Authority Required benefit for the treatment, in combination with prednisone or prednisolone, of castration resistant metastatic carcinoma of the prostate in a patient who meets certain criteria.”
(author’s note: The request by Janssen to the PBAC for consideration at it November, 2012 meeting (see extract above), basically reverting to the wording used in March, including a rider, viz., “ … of castration resistant metastatic carcinoma of the prostate in a patient who meets certain criteria.” construed to mean those who have failed chemotherapy and to still exclude the chemotherapy-naive “excluded” group that I have identified (see above).)
Copy:
"My
Consumer Comment (also my clinical comment as a retired medical practitioner and
medical administrator in community and public health)
Following radical prostatectomy and radiotherapy
I have been treated with IM Lucrin depot which kept my PSA down for three years but
I am now “hormone refractory”
The real new hope for
"post-chemotherapy" mCRPC and "chemotherapy-naïve" mCRPC
patients (like me) resides in two seminal events:
1.
In September 2012 the final analysis of the COU-AA-301 study was published
online in Lancet Oncology confirming that abiraterone significantly prolongs
overall survival in patients with metastatic castrate resistant prostate cancer
(mCRPC) who have progressed after docetaxel treatment. No new safety signals
were identified with increased follow-up, and
2.
The highly significant comments made in June, 2012 at the ASCO Conference in Chicago , viz.,
"Abiraterone
Delays Progression in Patients with Chemotherapy-Naïve CRPC: In patients with
asymptomatic or mildly symptomatic chemotherapy-naïve metastatic
castration-resistant prostate cancer (mCRPC), abiraterone acetate (AA) plus
prednisone produced a statistically significant benefit in radiographic
progression-free survival (rPFS) over placebo plus prednisone, according to a
planned interim analysis of a phase III study"
More than a year ago the EU, UK and USA approved the subsidy of
abiraterone basically on the same terms as the Australian Sponsor’s request for
listing in March 2012. Meanwhile it is still not listed on the PBS despite
repeated consideration by the PBAC since November 2011.
The obvious remaining factor denying access to abiraterone for the
“post-chemotherapy” patients is “cost-minimization”. Compared with
the evident benefit in regard to significant extension of life and amelioration
of symptoms cost should not be a consideration. It isn’t in other diseases such
as HIV aids where lives are also at stake.
A second group excluded from receiving the obvious benefits of abiraterone
comprises“chemotherapy-naïve” mCRPC
patients (excluded ones including myself). Just like “post-chemotherapy” patients
these men also have advanced cancer.
They too are incurable and the outcome for them is invariably fatal. The TGA approval of March 2012 did not include
them but they also are on death row like those who have had docetaxel,
mitoxantrone and cabazitaxel. It’s just they are at an earlier stage. They will
have to get worse even though there is an effective and less harmful remedy
available, abiraterone, all because of “cost-minimization”.
The TGA has already approved abiraterone for patients in the “post-chemotherapy” group. There is an urgent need for the TGA to
approve the drug for the“chemotherapy-naïve”
mCRPC group as well. The benefits and safety for the latter group were
declared at the ASCO Conference in Chicago in June 2012. These
patients urgently need a reprieve before their condition worsens. TGA approval
would clear the way for the PBAC to recommend a PBS subsidy for this group as
well.
As for cost-effectiveness, the base price of abiraterone seems to
compare favourably with published costs of taxane chemotherapeutic drugs and
“best supportive care” (BSC ) both of which have
known costly components. Oral administration gives abiraterone a cost
advantage. BSC and chemotherapy attract additional costs
including IV administration, use of hospital beds and staff, treatment of side
effects, analgesia and palliative care radiotherapy. In any case, to weigh some
residual cost-saving against a patient’s best interests goes against a
fundamental principle of justice in our society.
Neither should cost-saving become a lottery
where some diseases are permitted high-cost treatments while others are not.
Just as Burroughs Wellcome was induced (by popular protest) to offer a 36%
lower price for AZT in 1989, price negotiation remains a further tool in the
process of cost-minimization. Agreement on price by sponsor and government must
be achieved. It should not be allowed to roll over for further reconsideration
at future PBAC meetings which would mean more delay while lives are literally
at stake.
Until TGA approval is given for inclusion of the“chemotherapy-naïve” mCRPC group, saving money will continue to have greater weight than delaying the development of overt metastases and painful complications like spontaneous fractures of vertibrae and spinal nerve compression. Who could look even one patient in the eye and say, you can have chemotherapy with all of its downside but no, you may not have the drug abiraterone that could delay all this suffering and extend your life, all because it costs too much.
I therefore ask the PBAC at its November 2012 meeting to
recommend an immediate subsidy for abiraterone on the PBS for the “post-chemotherapy” group and do what is necessary to press the
TGA to broaden its current approval to include“chemotherapy-naïve” mCRPC patients, this to be followed by an immediate
subsidy for them also. For those of us with the disease this is a matter of
life or death.
Yours
sincerely, ”
November 2012 PBAC Outcomes - Positive Recommendations
LISTING
REQUESTED BY SPONSOR
http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/pbac-outcomes/2012-11/positive-recommendations
Requests a review of the PBAC’s
March 2012 recommendation to list abiraterone on a cost minimisation basis to
cabazitaxel as an Authority Required benefit for the treatment, in combination
with prednisone or prednisolone, of castration resistant metastatic carcinoma
of the prostate in a patient who meets certain criteria.
PBAC
RECOMMENDATION
The PBAC recommended listing on a
cost-minimisation basis with cabazitaxel and cost‑effectiveness basis when
compared with best supportive care
It may
take several months to receive Ministerial and Cabinet
approval, which could still be denied. Even if a PBS subsidy is approved, it
will benefit only those patients with incurable prostate cancer who have failed
treatment with chemotherapy. Those who have not had chemo first will not be
eligible. Unlike the FDA in the USA, The Therapeutics Goods Administration (TGA) in Australia has not given approval
for these patients. Without such approval no application for PBAC consideration
is possible under the "rules". As a consequence about 2,000
Australian men will inevitably develop painful secondaries forcing them onto
chemotherapy. They are being left without access to this effective treatment
that offers a pain-free extension of life. If the Government so decided, this process could and should be expedited)
Blog updated 17Feb13
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