1 / 20

Treatment of Recurrent Platinum-Refractory Ovarian Cancer

Treatment of Recurrent Platinum-Refractory Ovarian Cancer. Andreas du Bois Dept. Gynecology & Gynecologic Oncology Wiesbaden, Germany. AGO-OVAR Definitions of Platinum Sensitivity*. (potentially) platinum-sensitive disease: no prior chemotherapy

alanna
Download Presentation

Treatment of Recurrent Platinum-Refractory Ovarian Cancer

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Treatment of Recurrent Platinum-Refractory Ovarian Cancer Andreas du Bois Dept. Gynecology & Gynecologic Oncology Wiesbaden, Germany

  2. AGO-OVAR Definitions of Platinum Sensitivity* • (potentially) platinum-sensitive disease: • no prior chemotherapy • orresponse to prior platinum-based Tx or no evidence • of disease after prior platinum (CR, PR, NED) • and relapse after treatment free interval > 6 months • platinum-refractory disease: • no response to prior platinum-based Tx (NC, PD) • or PD free interval < 6 months after prior platinum Tx * A. du Bois et al. 1997

  3. Treatment modalities in Platinum-resistent Recurrent Ovarian Cancer: Surgery few selected pts. (e.g. bowel obstruction) Pt based therapy mainly pt-sensitive ROC Radiotherapy few selected pts. non-Pt combination Tx Endocrine TX Selected pts., rather 3rd/4th line ? non-Pt mono-Tx Supportive care every pt. as needed Psy-Soc Support every pt. as needed “new drugs“ only in clinical trials

  4. What is the Evidence – 9/2008 ? • Randomised Studies in Recurrent OC: • Studies Pts. • mono- vs. mono chemotherapy 10 2.195 • mono: schedule/dose/application 7 1.614 • mono- vs. endocrine therapy 2 303 • endocrine vs. endocrine therapy 2 106 • combination vs. combination 2 107 • mono vs. combination* 14 3.499 • all: 37 7.924 • * Including 1 trial with multiple regimens according to testing; most other trials • in pts. with platinum sensitive relapse

  5. TCA Ovarian Cancer Trial A prospective randomised controlled trial of tumour chemosensitivity assay directed chemotherapy versus physician’s choice in patients with recurrent platinum-resistant ovarian cancer. Ian A Cree,on behalf of the TCA Ovarian Cancer Trial Group Methode: ATP-based Tumor Chemosensitivity Assay (ATP-TCA) Andreotti et al., Cancer Research 1995; 55: 5276-82

  6. Patients - tested drugs/combinations • cisplatin • gemcitabine • cisplatin + gemcitabine • doxorubicin (Doxil/Caelyx) • paclitaxel • mitoxantrone • mitoxantrone + paclitaxel • topotecan • treosulfan • treosulfan + gemcitabine • treosulfan + epirubicin • cisplatin (x2) + etoposide • etoposide Physicians choice: mainly single agent therapy

  7. Results: Chemosensitivity-Assay without any Impact on Outcome Median PFS: HR: 0.80, 95%CI 0.59 - 1.10 Physician’s choice: 93 days Assay-directed: 104 days = + 11 days (median) Median OS: HR: 1.01 95%CI 0.7-1.3 Physician’s choice: 260 days Assay-directed: 261 days = + 1 day (median)

  8. mono vs. combination chemotherapy in refractory recurrent OC 103 pts. Melphalan 8 mg/m² d1-4 q28 R Pater JL 1987, Cancer Treat Rep Melphalan 6 mg/m² d1-4 q28 Hexa-MM 120 mg/kg d1-14 q28 102 pts. results: OR 2% vs 3% (combi), PFS and OS n.a. 41 pts. Paclitaxel 175 mg/m² 3h q28 R Bolis G 1999, Gynecol Oncol Paclitaxel 150 mg/m² Epirubicin 120 mg/m² q28 40 pts. results: OR 17% vs. 34% (combi), PFS n.a. 2-YSR 10% vs. 18% (n.s.)

  9. mono vs. combination chemotherapy in refractory recurrent OC 106 pts. ≤ 12 mos. Paclitaxel 175 mg/m² 3h q21 R Buda A 2004, Br J Cancer Paclitaxel 175 mg/m² Epirubicin 80 mg/m² q21 106 pts. results: OR 47% vs. 37% (combi), PFS 6 vs. 6 mos. OS 14 vs. 12 mos. (n.s.) 178 pts. Topotecan 1.25 mg/m² d1-5 q21 177 pts. R Topotecan 1.0 mg/m² d1-5 Etoposid 50 mg po d 6-12 q21 Sehouli J 2008, JCO 147 pts. Topotecan 0.5 - 0.75 mg/m² d1-5 Gemcitabine 800 mg/m² d1 + 600 mg/m² d8 q21 app. 20% refractory 41% > 12 Mon. results: OR 36% (TE) vs. 32% (TG) vs. 28 % (Topo) mean PFS 15 vs. 13 vs. 13 months (n.s.) mean OS 23 vs. 18 vs. 24 months (n.s.)

  10. mono vs. combination chemotherapy in refractory recurrent OC 118 pts. Doxil/Caelyx (PLD) 50 mg/m² q28 R BJ Monk et all , ESMO 2008 Trabectedin 1.1 mg/m² q 21 + Doxil/Caelyx (PLD) 30 mg/m² q28 113 pts. results: OR 12,2% vs 13,4% (combi; n.s.), PFS/OS n.s. PFS events: 163 HR: 0.95 (0.70-1.30) P = 0.7540 by courtesy of BJ Monk et al (Email: bjmonk@uci.edu) Trabectedin+PLD 4.0 mos PLD 3.7 mos

  11. Treatment modalities in Platinum-resistent Recurrent Ovarian Cancer: Surgery few selected pts. (e.g. bowel obstruction) Pt based therapy mainly pt-sensitive ROC Radiotherapy few selected pts. Today, no strong evidence supporting combination Tx outside trials (eg.DOVE) Endocrine Tx Selected pts., rather 3rd/4th line non-Pt mono-Tx Supportive care every pt. as needed Psy-Soc Support every pt. as needed “new drugs“ only in clinical trials

  12. What is the Evidence – 9/2008 ? • Randomised Studies in Recurrent OC: • Studies Pts. • mono- vs. mono chemotherapy 10 2.195 • mono: schedule/dose/application 7 1.614 • mono- vs. endocrine therapy 2 303 • endocrine vs. endocrine therapy 2 106 • combination vs. combination 2 107 • mono vs. combination* 14 3.499 • all: 37 7.924 • * Including 1 trial with multiple regimens according to testing; most other trials • in pts. with platinum sensitive relapse

  13. AGO-OVAR 2.3 (Stratum 1, Relapse within 6 mos. after Platinum-Paclitaxel) 65 pts. Treosulfan 7 g/m² iv q21 R Meier W 2003, ASCO Topotecan 1,5 mg/m² d1-5 q21 63 pts. PFS OS OR 19.3% (topo) vs 7.0% (p=.0524), OS n.s. (+3,9 mos. for topo), PFS significantly superior after topotecan (median +2 mos.)

  14. mono vs. mono chemotherapy in recurrent (mostly) refractory OC - RCTs 114 pts. 50% refractory, but „only“ to platinum Paclitaxel 175 mg/m² 3h iv q21 R ten Bokkel Huinink 1997, J Clin Oncol Topotecan 1,5 mg/m² iv d1-5 q21 112 pts. results: OR 14% vs. 21% (Topotecan) median PFS 15 vs. 19 months (n.s.) median OS 53 vs. 63 months (n.s.) Cave: patients had no taxans during 1st-line … but today, most patients had platinum plus taxan-containing 1st-line therapy! Therefore, data support mainly Topotecan.

  15. mono vs. mono chemotherapy in recurrent (mostly) refractory OC - RCTs Paclitaxel 175 mg/m² 3h iv q21 107 pts. 62% refractory, but „only“ to platinum R O’Byrne 2002, ASCO Caelyx 50 mg/m² iv q28 106 pts. results: OR 23% vs 19% (Caelyx; n.s.) median PFS 4.4 vs. 4.8 months (n.s.) median OS 13 vs. 11 months (n.s.) Cave: patients had no taxans during 1st-line … but today, most patients had platinum plus taxan-containing 1st-line therapy! Therefore, data support mainly Caelyx.

  16. mono vs. mono chemotherapy in recurrent (mostly) refractory OC - RCTs 235 pts. 55% Pt.-refractory, > 70% prior taxans Topotecan 1,5 mg/m² iv d1-5 q21 Gordon 2001, J Clin Oncol 2004, Gynecol Oncol R Caelyx 50 mg/m² iv q28 239 pts. Results platinum refractory subgroup: Caelyx (130) Topotecan (124) p-value PFS (weeks, median) 9,1 13,1 0.733 OS (weeks, median) 36 41 0.455 G3/4 toxicity (all pts.;%) Neutropenia 12 77 < 0.001 Anemia 5 28 < 0.001 Thrombocytopenia 1 34 < 0.001 Leukopenia 10 50 < 0.001 Treatment-related sepsis 0 4 < 0.001 Alopecia (all grades) 16 49 0.007 Hand-Foot-Syndrom 23 0 < 0.001 Stomatitis 8 0.4 < 0.001

  17. mono vs. mono chemotherapy in recurrent (mostly) refractory OC - RCTs 232 pts. 3rd-line after platinum-taxan and caelyx or topotecan 2nd-line Canfosfamid 1000 mg/m² iv d1 q21 R Vergote 2007, ASCO Caelyx 50 mg/m² iv q28 or Topotecan 1.5mg/m² iv d1-5 q21 229 pts. Results: canfosfamide inferior compared to standard arm

  18. mono vs. mono chemotherapy in recurrent (mostly) refractory OC - RCTs 99 pts. Gemcitabine 1000 mg/m² d1+8 q21 66 pts. R Mutch, JCO 2007 Caelyx 50 mg/m² d1 q28 64 pts. 96 pts. Results: *Statistically significant.

  19. mono vs. mono chemotherapy in recurrent (mostly) refractory OC - RCTs 77 pts. 100% platinum-taxan, TFI < 12 mos. (57% < 6 mos.) Gemcitabine 1000 mg/m² d1,8, 15 q28 Mito-3 G Ferrandina et al JCO 2008 R Caelyx 40 mg/m² d1 q28 76 pts. Results: OR 16% vs. 18% (Gem), OR duration 18 vs. 17 (Gem) weeks ; n.s. QoL advantage for caelyx in 2 of 4 time points (p < 0.05)

  20. Treatment modalities in Platinum-resistent Recurrent Ovarian Cancer: Surgery few selected pts. (e.g. bowel obstruction) Pt based therapy mainly pt-sensitive ROC Today, no strong evidence supporting combination Tx outside trials (eg.DOVE) Radiotherapy few selected pts. • 1st choice: • non-Pt mono-Tx • Caelyx • Topotecan • Gemcitabine Endocrine Tx Selected pts., rather 3rd/4th line Supportive care every pt. as needed Psy-Soc Support every pt. as needed “new drugs“ only in clinical trials

More Related