Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in...
Transcript of Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in...
![Page 1: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/1.jpg)
Mitoxantrone* 12.7
4 studies report a significant improvement of OS in CRPC after docetaxel failure.
Placebo* 11.2
Placebo 13.6
Alpharadin 14.0
Overall Survival
Cabazitaxel* 15.1
Abiraterone* 15.8
MDV3100 18.4
Placebo 11.2
Mitoxantrone* 3.1
Placebo* 6.6
Placebo 2.9
Cabazitaxel* 6.4
Abiraterone* 10.2
MDV3100 8.3
PSA-PFS
* Plus Prednisone
![Page 2: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/2.jpg)
Study-Analysis
3 AGENTS with positive results but trials no comparable(differences in patients-characteristics, PSA level, presence of pain, criteria of
evaluation, progression criteria)
![Page 3: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/3.jpg)
•There are no randomized trials comparing these 3 agents-No predictive models or biomarkers that are able to identify patients who are likely to benefit from any of these drugs
Choice of therapy is based on clinical expertise
![Page 4: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/4.jpg)
Gleason Score, HT and OSTropic and EAP posthoc analysis
Conclusioni:•OS e PFS in patients treated with Cabazitaxel not related to:
– Gleason Score (0-7; 8-10)– Duration of HT pre-TXT (+/- 20 Months )
•Multivariate analysis: SHORT OS and PFS in pts with low PS (ECOG 2), high ALP and PAIN
Oudard et al, ASCO GU 2013
![Page 5: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/5.jpg)
Univariable
Months of Prior Hormonal Therapy 0.96 (0.92, 0.99) 0.019
Time to PD Following Docetaxel 0.98 (0.89, 1.09) 0.75
Prior Cycles of Docetaxel 0.99 (0.93, 1.06) 0.80
Age 0.97 (0.93, 1.01) 0.11
Baseline PSA (/100) 0.93 (0.77, 1.11) 0.42
PSA Doubling Time 0.95 (0.84, 1.08) 0.46
Gleason Score 0.86 (0.64, 1.16) 0.33
Gleason Score, ≥8 versus ≤7 0.50 (0.26, 0.95) 0.033
Visceral Disease 2.74 (1.33, 5.65) 0.006
ECOG, 1 versus 0 1.28 (0.83, 1.98) 0.27
Prior Abiraterone 1.58 (0.55, 4.48) 0.39
Multivariable
Visceral Disease 4.16 (1.86, 9.30) <0.001
Gleason Score, ≥8 versus ≤7 0.36 (0.18, 0.72) 0.004
Future Oncology 2013
![Page 6: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/6.jpg)
Predictors of poor response to ABI
• 408 mCRPC pts enrolled in 19 centres• Gleason at diagnosis:
– 8-10: 51.2%– 7: 36.1%– <7: 12.7%
• Median duration of ABI therapy: 6.1 months• Predictors of poor response to ABI:
– Univariate: age, Gleason, number of mets, baseline PSA, duration of HT, number of lines of chemo, duration of chemo
– Multivariate analysis: Gleason 8-10predict POOR response to ABI
Azria et al. ASCO GU 2012 (poster 149)
![Page 7: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/7.jpg)
Is primary refractoriness to docetaxel a potentialpredictive variable?
Di Lorenzo et al (Eur Urol, 2013)
![Page 8: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/8.jpg)
Cabazitaxel reduces the risk of death in primaryrefractory patients
Di Lorenzo et al (2013, Eur Urol)
![Page 9: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/9.jpg)
Angelergues et al, Abst 5063, ASCO 2013
• Conclusions: patients treated with 2 prior Docetaxel lines, PSA response >30% with Cabazitaxel and treated with new hormonal agents after Cabazitaxel experienced prolonges OS.
• Conversely intake of new hormonal agents before Cabazitaxel rather after wasassociated with a reduced OS from the first Docetaxel.
• Prospective randomized trials are needed.
•125 pts treated with cabazitaxel and retrospectively analyzed.
•Median OS from the first docetaxel was 65 mo in patients treated with abiraterone/enzalutamide after Cabazitaxel vs 39 mo in patients receiving these agents before Cabazitaxel.
![Page 10: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/10.jpg)
Esmo 2013
![Page 11: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/11.jpg)
-Long term response to ENZALUTAMIDE: >12 MONTHS: 35%
-These pts had less disease burden
![Page 12: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/12.jpg)
PS 2: HT
9% PS 2
![Page 13: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/13.jpg)
Androgen levels
Serum Androgen is prognostic for OS in abiraterone patients
![Page 14: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/14.jpg)
Prognostic model to predict OS in men receiving second line chemotherapy
(Halabi et al ASCO 2013)
-Data from Tropic trial (cabazitaxel patients) -A separate data set was used for external validation-Predictive score was used to classify patients in low and high risk groupsConclusions:•9 prognostic variables: ECOG PS, time since last docetaxel use, measurable disease, presence of visceral disease, pain, duration of prior HT, hgb, PSA and ALP
•The median OS were 11 and 16 months in the high and low risk groups
![Page 15: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/15.jpg)
Prognostic model to predict OS in men receiving abiraterone
(Chi et al ASCO 2013, abstr. 5013)-Data from COU-AA 301Following risk factors were associated with poor prognosis: 1) ECOG PS of 2 (HR 2.19),2) presence of liver metastases (HR: 2)3) Time from start of initial LHRH-agonist to start of Abir (<36 months) (HR:1.3)4) Low albumin (HR1.54)5)High ALP (HR:1,38)6) High LDH (HR: 2.31)CONCLUSIONS:Patients categorized in 3 risk groups: 0-1 good: OS 21.3 mo2 or 3 intermediate: OS 13.9 mo4 to 6: poor: OS 6.1 mo
![Page 16: Presentazione di PowerPointMitoxantrone* 12.7. 4 studies report a significant improvement of OS in CRPC after docetaxel failure. Placebo* 11.2. Placebo 13.6. Alpharadin 14.0. Overall](https://reader036.fdocuments.in/reader036/viewer/2022070720/5ee084acad6a402d666bb020/html5/thumbnails/16.jpg)
Suggested choice in second line for mCRPC (expert opinion)
GLEASON SCORE ( >7) : cabazitaxelShort prior HT before CT ( 24): cabazitaxelPD during DOCETAXEL (primary ): cabazitaxelPD during DOCETAXEL ( acquired): both options
CT-CT-HT vs CT-HT-CT sequence: cabazitaxelPS: 2 abiraterone/enzalutamideVisceral metastases (liver): cabazitaxelHigh Serum androgen levels: abiraterone/EnzalutamideTOXICITY to prior treatment: abiraterone/enzalutamide
TO BE CONSIDER: AGE and Comorbidity : liver, hematologic, Hypertension and
cardiac disorders