DEJEUNER-DEBAT Alternatives d administration des chimiothérapies (Session Plénière ) Salle : Salle Camille Blanc

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1 DEJEUNER-DEBAT Alternatives d administration des chimiothérapies (Session Plénière ) Salle : Salle Camille Blanc Revue des essais cliniques en cours et perspectives Dr Cristian Villanueva CHRU Besançon

2 Single-agent estramustine phosphate (EMP) is active in advanced breast cancer after failure with anthracyclines and taxanes L Zelek et al. Annals of Oncology 12 : , included patients 35 were evaluable for response PR 17.5% (95%CI 6%-30%) n=7 SD 25% (95%CI 12%-38%) n=10

3 EFESE STUDY DESIGN - Randomized open phase II study RE +, HER2- MBC (N=100) 1:1 TAMOXIFENE 20 mg -No prior regimen of CT for MBC -prior regimen of IA for MBC ESTRAMUSTINE 140 mg bid - Primary end points: ORR - Key secondary end points: PFS, OS, safety, QoL, biological coagulation test UNICANCER

4 BEST STUDY DESIGN - Randomized open phase II study RH+HER2- MBC (N=300) BSC or any treatment -prior taxanes, anthracyclines, capecitabine & eribulin regimen of CT for MBC -prior regimen of HT for MBC 1:1 ESTRAMUSTINE 140 mg bid Continuous daily schedule (or days 1-28 of each 28 day cycle). There will be no rest in the schedule. - Primary end points: ORR - Key secondary end points: PFS, OS, safety, QoL, PI C Villanueva CHRU BESANCON

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6 VICTORIANE Study Rational and Design (Vinorelbine Clinical Trial Oral + Inhibitors Aromatase)

7 CURRENT ONGOING TRIALS IN HR + BREAST CANCER POST MENOPAUSAL Adjuvant First line Second line (or adj <12m) Third line PENELOPE-B NSAI based PALOMA-2 MONALEESA-2 MONALEESA-7 (premenopausal) MONARCH-3 Fulvestrant based MONALEESA-3 MONARCH-2 Fulvestrant based SOLAR-1 Fulvestrant based BELLE-2 PALOMA-3 Other PEARL (with exemestane vs chemo) MONARCH-1 (single agent) BELLE-3

8 VICTORIANE Study Rational (Vinorelbine Clinical Trial Oral + Inhibitors Aromatase) - Hormonotherapy is standard first line treatment in ER+ MBC but around one half of patients respond. Mouridsen H. J Clin Oncol Jun 1;21(11): Chemotherapy is used in ER+ MBC and vinorelbine is among the agents. Cardoso F et al.breast Oct;23(5): Cardoso F, Ann Oncol Oct;23 Suppl 7:vii11-9). -Combined HT with vinorelbine was evaluated in some phase 2 trials, Taylor CW. Abst 504 SABCS 1996 Pawlicki M. Abst 460 ASCO 2000 Freire de Olivera. SOMPS 1997 Nardone L. Abst 58 EJC vol 33; 1997 Riggi M. Abst 600 ASCO 2009 Barni S. Abst 132 P ESMO 2004 Perez Manga G. Abst 756 ASCO

9 VICTORIANE Study Rational (Vinorelbine Clinical Trial Oral + Inhibitors Aromatase) - Oral chemotherapy offers significant advantages Findlay M. Ann Oncol Feb;19(2): Epub 2007 Nov 15. Review. - Metronomic chemotherapy is a low toxicity regimen André N, Nat Rev Clin Oncol Jul;11(7): Briasoulis E. BMC Cancer May 29;13:263 Rajdev L, Cancer Chemother Pharmacol Nov;68(5): Kontopodis E J Chemother Feb;25(1):49-55 Saloustros EUON Apr-Jun;16(2):215-8 Combined therapy between an HT and anti-proliferative drug will be future standard Finn RS. Lancet Oncol Jan;16(1):25-35 Baselga J. N Engl J Med.2012 Feb 9;366(6):520-9 Combined HT in association of metronomic chemotherapy oral versus HT alone have never been compared in a face to face III phase trial.

10 VICTORIANE Study Design (Vinorelbine Clinical Trial Oral + Inhibitors Aromatase) - Randomized open phase III study RE +, HER2- MBC (N=340) - Postmenopausal women - No prior regimen for MBC 1:1 - Stratification factors: visceral metastases (y vs n), adjuvant hormonal treatment (y vs n), center - Primary end points: PFS by investigator, - Key secondary end points: OS, and safety, ORR, QoL Letrozole 2,5 mg once a day or Anastrazole 1 mg once a day Oral vinorelbine 50 mg 3 times / w (M-W-F) + Letrozole 2,5 mg once a day or Anastrazole 1 mg once a day Continuous daily schedule (or days 1-28 of each 28 day cycle). There will be no rest in the schedule. PI: C. Villanueva, CHRU Besançon

11 CHEOPS (ARCAGY-GINECO) (Vinorelbine Clinical Trial Oral + Inhibitors Aromatase) - Randomized open phase II study RE +, HER2- MBC (N=120) 1:1 Oral vinorelbine 50 mg 3 times / w (M-W-F) - Postmenopausal women - No more 2 chemotherapy regimen for MBC Oral vinorelbine 50 mg 3 times / w (M-W-F) + Letrozole 2,5 mg once a day or Anastrazole 1 mg once a day Continuous daily schedule (or days 1-28 of each 28 day cycle). There will be no rest in the schedule. - Primary end points: PFS - Key secondary end points: OS, and safety, ORR CB 24 month QoL PI : Pierre-Etienne HEUDEL, CLB Lyon