ESMO SUMMIT AFRICA 2018 Practice changing studies in Prostate Cancer in 2016 and 2017 and cost-effectiveness Ronald de Wit
CONFLICT OF INTEREST DISCLOSURE Sub-title Sanofi Roche Merck Lilly
14 years of progress in the Management of Prostate Cancer mcrpc; 2011 paradigm shift Novel AR targeted agents pre-chemotherapy mhspc; 2014 paradigm shift Docetaxel in addition to ADT in men presenting with M1 disease mhspc; 2017 addition of abiraterone to ADT
Combination of ADT and taxanes CHAARTED (M1) STAMPEDE (M0/M1) Phase III randomized trial in 790 men with metastastic hormone-naïve PCa Phase III randomized trial in M0/M1 patients with hormone-naïve PCa DOC: Docetaxel 1Sweeney C et al. N Engl J Med. 2015;373:737-46; 2James N et al. Lancet. 2015, December
Treatment effect by metastatic status: Overall survival Pre-planned analysis +ZA +Doc +ZA+Doc
CHAARTED Update ESMO 2016
ESMO 2016; CHAARTED QL ADT +/- DOC FACT-P high volume FACT-P low volume
CHAARTED / STAMPEDE CHAARTED mature results ESMO 2016 Benefit only in high-volume patients ( 4 bone mets/visc m) HR in low-volume 1.04 STAMPEDE benefit in M1 pts, but % of high vs low volume pts not reported ; is benefit dictated by majority of high-volume patients? (85% had bonemets)
LATITUDE, ASCO 2017
Study design of LATITUDE Presented by: Karim Fizazi
LATITUDE: Co-primary End Points Figures included with permission, from Fizazi K, et al. N Engl J Med. 2017;377:352-360. CI, confidence interval; HR, hazard ratio; NR, not reached; rpfs, radiographic progression-free survival.
QL LATITUDE, ESMO 2017
ADT + AA + P Persistently Improved General Health Status (VAS) and EQ-5D- 5L Health Utility Scores
Subsequent life-prolonging therapy for prostate cancer double-blind study!! *Patients who discontinued treatment and were eligible for subsequent therapy. Presented by: Karim Fizazi
STAMPEDE ABI+ADT vs ADT in newly diagnosed locally advanced or metastatic PC (ASCO 2017) Phase 3 randomized trial in newly diagnosed M0/M1 prostate cancer. Primary end-point: OS FFS: failure free survival James ND et al. NEJM 2017; 377: 338-51
STAMPEDE abiraterone comparison OS by metastatic status pre-planned analysis (ASCO 2017)
STAMPEDE ( +/- abi/pred) ASCO 2017 Treatment started since first progression SOC = standard-of-care (ADT) AAP = abiraterone acetate + prednisolone James et al NEJM 2017
Conclusions Docetaxel/pred 18 weeks ; brief exposure QL in CHAARTED - LV at 9 months identical in both arms CHAARTED and STAMPEDE open label, choice subsequent lines not biased Strongest evidence for High Volume Abiraterone/pred(5mg) 3 years; 3 years extra visits, cardiovasc events, prednison adverse effects Evidence HV by LATITUDE criteria ( bone m/visc m Gl 9/10; 2 of 3 ) LATITUDE tested early abi vs no abi ( rather than abi at time of CRPC); only 13% of pts exposed to abi/enza at time of interim analysis and report Expensive( +/- 10 fold as compared with docetaxel)
Cost of treament: between ABIRATERONE or docetaxel in mhspc: Impact on economic health (Oudard ESMO discussant 2017) Computed for Georges Pompidou Med center, Paris, France 1. Fizazi K. NEJM 2017; 377:352-60; 2. James ND. NEJM 2017; 377: 338-51; 3. Sweeney C. NEJM 2015;373:737-46; 4. James ND Lancet 2016;387:1163-77
2 cohorts in STAMPEDE, ESMO 2017
STAMPEDE: SOC+DocP vs SOC
STAMPEDE: SOC+AAP vs SOC
STAMPEDE: SOC+AAP vs SOC+DocP
Overall survival (primary outcome measure]
Cause-specific survival
Adverse events worst toxicity ever
Adverse events prevalence at 1 year and 2 years
Summary of end-points
Is Docetaxel OR Abiraterone the right question? NO, combination might be the future BUT level 1 evidence is not yet there (Oudard, ESMO discussant 2017)
PEACE-1: European Phase III Trial in de novo Metastatic Prostate Cancer (revised 2x2 design)* (n=916)
Conclusions on CHAARTED / STAMPEDE CHAARTED mature results robust benefit by 6cy docetaxel; only in high-volume (HV) patients STAMPEDE benefit only in M1 pts, % of high volume unknown; benefit HV vs LV? Brief exposure ( 18 weeks) by the additional treatment QL after 6-9 months similar to the ADT only group in LV, but better than the HV group ( benefit) To date some information available of efficacy subsequent treatment Cheap!
Conclusions on LATITUDE / STAMPEDE LATITUDE provides similar OS benefit as compared with CHAARTED Bias due to inferior use of cross-over ( early abi vs no abi) More/ longer lasting side effects Robust benefit as compared with use in mcrpc setting, but evidence only in high-volume (HV) patients No supportive data for use of doce in HV and use of abi in LV ( LATITUDE had similar risk criteria) STAMPEDE benefit only in M1 pts, % of high-volume unknown 3 years abi/pred 10 fold more expensive ( computed for France)
In 2017 Multiple Choices and Sequences mhspc early taxane /late taxane mhspc early abi/late abi/enza mcrpc abi/enza predoce mcrpc abi/enza postdoce/ precaba/postcaba mcrpc Radium 223 pre or post taxane Efficacy individual drugs in subsequent lines not well defined