Supplementary File 2: EVITA vs. TRIP
Supplementary File 2: a comparison of TRIP database search results and EVITA
Abiraterone: metastatic castration-resistant prostate cancer (mCRPC)
CountryWales
(All Wales Medicines Strategy Group, SWMSG) / Recommendation / Yes
Justification / · Abiraterone with prednisone or prednisolone is recommended for the treatment mCRPC in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.
· This recommendation applies only in circumstances where the approved Wales Patient Scheme for access to medicines is utilised.
· AWMSG is of the opinion that abiraterone is suitable for specialist only prescribing within NHS Wales for the above indication.
Year / 2012
Germany
(Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen) / Recommendation / Yes
Justification / · The clinical evidence indicates a considerable additional benefit of abiraterone for the treatment of metastatic CRPC in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen with prednisone or prednisolone.
· Clinical benefit in terms of overall survival and pain.
Year / 2013
Austria
(Institute for Health Technology Assessment, Ludwig Boltzmann Gesellschaft) / Recommendation / No clear decision
Justification / · The landscape for mCRPC therapy is rapidly evolving and several agents have shown increased OS for mCRPC after docetaxel therapy.
· The gains of about 4 months in OS in addition to an acceptable safety profile indicate that abiraterone is currently the most beneficial therapy.
· The optimal sequencing of these drugs still remains unknown.
· In order to ultimately identify the best regimen, reliable data for QoL are needed for all treatment options.
Year / 2011
Scotland*
(The Scottish Medicines Consortium, SMC) / Recommendation / Yes (restricted use in patients with mCRPC after chemotherapy)
Justification / · Following a re-submission: Abiraterone acetate is accepted for restricted use with prednisone or prednisolone for the treatment of mCRPC in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen within NHS Scotland. SMC restriction: abiraterone is restricted to use in patients who have received only one prior chemotherapy regimen. Abiraterone plus prednisone was associated with significantly improved overall survival compared with placebo plus prednisone in patients with mCRPC previously treated with docetaxel. The SMC advice takes account of the benefits of a Patient Access Scheme (PAS) that improves the cost-effectiveness of abiraterone (contingent advice).
Year / 2012
UK (except Scotland)
(National Institute for Health Research NHS, NICE) / Recommendation / Yes
Justification / · Abiraterone, in combination with prednisone or prednisolone, is recommended as an option for the treatment of mCRPC in adults only if:
1. their disease has progressed on or after one docetaxel-containing chemotherapy regimen, and
2. the manufacturer provides abiraterone with the discount agreed in the patient access scheme.
· The Committee concluded that the available evidence demonstrated that abiraterone was a clinically effective second-line treatment for castration-resistant metastatic prostate cancer.
· The Committee concluded that abiraterone offers a step change in treatment because it is an oral drug taken by patients at home and is associated with few adverse reactions.
· The Committee agreed that the ICER was likely to be less than £50,000 per QALY gained.
· The Committee concluded that abiraterone fulfilled the criteria for consideration as a life-extending, end-of-life treatment.
· The Committee also concluded that the additional weight that would need to be assigned to the original QALY benefits in this patient group was within the range considered acceptable for an end-of-life treatment.
Year / 2012
EVITA
(EValuation of pharmaceutical Innovations with regard to Therapeutic Advantage) / EVITA score / Treatment / Category I / Trial setting A2 / Score 6.5
TRIP vs. EVITA / · Abiraterone is a new approach for the treatment of mCRPC after previous docetaxel chemotherapy, hence EVITA trial setting A2.
· EVITA only evaluates therapeutic benefit, as opposed to a benefit-to-treatment cost ratio (e.g., in Scotland).
· The EVITA score was likely to be high due to not having a comparable treatment already established.
· The EVITA score is likely to change with the addition of more studies, and could be even higher since an additional study showing a significant benefit would raise the efficiency score by an additional 2.5 points resulting in an EVITA score of 9 (if the outcomes are the same).
· It is important to notice that the decision if an EVITA-score is accurate, the trial setting must be considered.
*Another resubmission for the chemotherapy-naïve indication, which abiraterone is currently not approved for, was expected to be submitted in December 2013.
Enzalutamide: metastatic castration-resistant prostate cancer (mCRPC)
CountryUSA
(BlueCross BlueShield Association) / Recommendation / No clear decision
Justification / · Evidence on enzalutamide was produced by one single-arm study of 65 patients with no health outcome benefit data. It is difficult to judge whether patients benefit from enzalutamide when there are no studies comparing them with active treatment or natural history of disease.
· In the setting of post-docetaxel second-line therapy, evidence demonstrates survival benefit.
· Studies are insufficient to show a beneficial impact from enzalutamide because of no comparison with other active treatment or natural history of disease.
Year / 2013
Germany
(Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen) / Recommendation / Yes
Justification / · The additional benefit of enzalutamide in adult men with metastatic CRPC whose disease has progressed on or after docetaxel therapy depends on the presence of visceral metastasis.
Year / 2013
Austria
(Institute for Health Technology Assessment, Ludwig Boltzmann Gesellschaft) / Recommendation / No clear decision
Justification / · Recent therapeutic advances for managing advanced prostate cancer offer new treatment options, including enzalutamide for patients with mCRPC. Multiple challenging questions as how to best combine, optimally sequence, and select agents for treatment (like abiraterone acetate, cabazitaxel, enzalutamide) are therefore emerging and should be addressed in further clinical trials.
Year / 2013
Scotland
(The Scottish Medicines Consortium, SMC) / Recommendation / Yes: Enzalutamide is accepted for use within NHS Scotland
Justification / · Treatment of adult men with mCRPC whose disease has progressed on or after docetaxel therapy.
· In one randomised, double-blind, phase III clinical study, enzalutamide significantly increased overall survival compared with placebo.
· This SMC advice takes account of the benefits of a Patient Access Scheme (PAS) that improves the cost-effectiveness of enzalutamide. This SMC advice is contingent upon the continuing availability of the PAS in NHS Scotland or a list price that is equivalent or lower.
Year / 2013
UK
(National Institute for Health Research NHS, Horizon Scanning Centre) / Recommendation / No decision yet
Justification / · Enzalutamide is in a phase III clinical trial comparing its effect on overall and progression-free survival against treatment with placebo. This trial is expected to complete in September 2014.
· If licensed for this indication, enzalutamide may provide an additional treatment option for this patient group, who currently have limited effective therapeutic options.
Year / 2012
EVITA
(EValuation of pharmaceutical Innovations with regard to Therapeutic Advantage) / EVITA score / Treatment / Category I / Trial setting A2 / Score 6.5
TRIP vs. EVITA / · Enzalutamide is a new approach for patients with mCRPC after previous docetaxel chemotherapy, hence EVITA trial setting A2.
· A randomized study with 1199 patients showed an ARR of the OS after 1 year (30%), thus earning an efficiency score of 6.5.
· The EVITA score was likely to be high due to not having a comparable treatment already established
· The EVITA score is likely to change with the addition of more studies and could be even higher, since an additional study showing significant benefit would raise the efficiency-score by an additional 2.5 points resulting in an EVITA score of 9 (if the outcomes are the same).
· It is important to notice that the decision if an EVITA-score is accurate, the trial setting must be considered
Sipuleucel-T: metastatic castration-resistant prostate cancer (mCRPC)
CountryUSA
(BlueCross BlueShield Association) / Recommendation / No clear decision
Justification / · Sipuleucel-T resulted in a median survival advantage of 4.1 months with a 3-year survival rate of 31.7%, compared with 23.0% in those receiving placebo.
· Survival was improved for patients who had an antibody titre of more than 400 against PA2024 or prostatic acid phosphatase (PAP) at any time after baseline (P<0.001), but not for those who had T-cell proliferation responses to PA2024 or PAP measured at week 6.
· However, sipuleucel-T offered no evidence of a measurable antitumor effect.
· For now, access to sipuleucel-T will be limited to a subset of the Phase III trial sites. Manufacturing capacity is expected to increase over time.
Year / 2010
USA
(BlueCross BlueShield Association) / Recommendation / No decision yet
Justification / · The effect of sipuleucel is not apparent early in the course of the disease after treatment and only in the context of a substantial amount of eventual chemotherapy.
· It would be important to understand the existence of, and nature of, interactions between sipuleucel and subsequent treatments.
· The current existing analyses are insufficient to know to what degree sipuleucel is effective in the absence of chemotherapy, or depends on chemotherapy, to demonstrate improvement in survival. Such information is critical for the decisions physicians and patients need to make as they plan how to treat the patient’s cancer.
Year / 2011
UK
(National Institute for Health Research, NHS) / Recommendation / No decision yet
Justification / · The prognosis of the current indication of these vaccine products (sipuleucel-T and Prostvac-VF) is a median survival between 20 and 30 months. Demonstration of a survival benefit among candidate patients at earlier stages of disease would require much longer periods of study due to the greater baseline prognosis of these patients. However, without such studies, it would be premature to extend the indications for such vaccines (if any are proven to be effective for the current indication).
Year / 2011
USA
(BlueCross BlueShield Association, Technology Evaluation Center) / Recommendation / No clear decision
Justification / · Evidence indicates a survival advantage for sipuleucel-T as first-line systemic therapy in patients with mCRPC. Results are limited to patients with asymptomatic or minimally symptomatic mCRPC; no studies have been conducted in patients with moderate to severe symptomatic mCRPC.
· No studies have been conducted in patients with moderate to severe symptomatic mCRPC. Studies are insufficient to show a similarly beneficial impact from abiraterone acetate or enzalutamide because none compare these treatments with other active treatments or the natural history of the disease.
· No head-to-head comparison in the same study.
Year / 2013
Canada
(Canadian Coordinating Office for Health Technology Assessment) / Recommendation / No decision yet
Justification / · There are no therapeutic vaccines approved for use for prostate cancer in Canada or the US.
· To be effective, a therapeutic vaccine must demonstrate the ability to elicit an appropriate tumour-specific response and have a favourable safety profile.
· Sipuleucel-T is safe and well tolerated. It targets a specific protein for prostate cancer and demonstrates a statistically significant survival benefit. Further clinical trials should compare sipuleucel-T with the current treatment standard (docetaxel plus prednisone).
Year / 2006
EVITA
(EValuation of pharmaceutical Innovations with regard to Therapeutic Advantage) / EVITA score / Treatment / Category I / Trial setting “?” / Score 8.5
TRIP vs. EVITA / · There are 3 randomized studies in which sipuleucel-T was given as an add-on, rather than compared with standard treatment (docetaxel) or to placebo. Hence, the trial setting was set to “?”.
· The ARR of the OS after 1 year was between 7% and 8%, which results in an efficiency score of 8.5.
· It is important to notice that the decision if an EVITA score is accurate, the trial setting must be considered.
Prostvac: chemotherapy-naïve hormone-relapsed prostate cancer
CountryUSA
(BlueCross BlueShield Association) / Recommendation / No decision yet
Justification / · Prostvac is currently in a phase III clinical trial comparing its effect on overall survival against treatment with placebo. This trial is expected to complete in August 2016.
· If licensed, Prostvac will offer an additional treatment option for asymptomatic or minimally symptomatic hormone-relapsed prostate cancer. Prostvac has the potential to improve the effectiveness of immunotherapy treatment through a heterologous prime/boost immunogenic strategy.
Year / 2013
UK
(National Institute for Health Research, NHS) / Recommendation / No decision yet
Justification / · The prognosis of the current indication of these vaccine products (sipuleucel-T and Prostvac-VF) is a median survival between 20 and 30 months. Demonstration of a survival benefit among candidate patients at earlier stages of disease would require much longer periods of study due to the greater baseline prognosis of these patients. However, without such studies, it would be premature to extend the indications for such vaccines (if any are proven to be effective for the current indication).
Year / 2011
EVITA
(EValuation of pharmaceutical Innovations with regard to Therapeutic Advantage) / EVITA score / Treatment / Category I / Trial setting “?” / Score 6
TRIP vs. EVITA / · There is one randomized study that qualifies for an EVITA evaluation, in which Prostvac was given as an add-on, rather than compared to the standard treatment (docetaxel) or placebo. Hence the trial setting was set to a “?”.
· The ARR of the OS after 1 year was 4%, which results in an efficiency score of 6.
· It is important to notice that the decision if an EVITA-score is accurate, the trial setting must be considered.
Radium 223: bone metastases in castration-resistant prostate cancer
CountryUK
(National Institute for Health Research, NHS) / Recommendation / Not available
Justification / -
Year / 2014
EVITA
(EValuation of pharmaceutical Innovations with regard to Therapeutic Advantage) / EVITA score / Treatment / Category I / Trial setting A2 / Score 9
TRIP vs. EVITA / · Radium 223 is a new approach to treat bone-metastasis in CRCP patients, as until now bisphosphonates and beta-emitting radioisotopes have been used; however, there is no established standard-treatment.
· There were 2 randomized studies in which radium 233 was compared to placebo, hence a trial setting of A2.
· The ARR of the OS after 50 weeks was ca. 16%.
· It is important to notice that the decision if an EVITA-score is accurate, the trial setting must be considered.
Ipilimumab: advanced (unresectable or metastatic) melanoma