Practice Guideline for Gynecologic Cancer v 2.0, 2010 Ovarian Cancer Guideline Tae Joong, Kim Department of OB/GYN Samsung Medical Center Sungkyunkwan Univ. School of Medicine
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V 2.0. 2010 vs. V 1.1. 2007 2008 FIGO ( ) NCCN / Class III/IV / Key questions (8 )
2008 10 15 2003-2005 1,512 1.1% 17, 10. 10 6.3. 40 23.2%, 50 21.8%, 60 17.5%.
ʻ V1.1, 2007ʼ, key questions, /.
/ (1) Clear cell pathology grade 3 CT 1,. class III ( ), class III
/ (2) 8 Adjuvant consolidation radiation therapy 2 2-4, 3 3-6 2 2-4
1. Clear cell carcinoma? D (very low) 10 NRS (9 retrospective, 1 prospective study) 7 studies: poor prognosis
Prognosis of ovarian clear cell carcinoma compared to other histological subtypes: A meta-analysis Yoo-Young Lee, Tae-Joong Kim et al. Gynecol Oncol, 2011, 122, 541 Methods. From January 1974 to February 2011, we identified a total of 31,800 (CCC; 2152, non-ccc; 29648) patients from 12 studies meeting the inclusion criteria. Results. Heterogeneity tests demonstrated significant between-study variation (I 2 =92.1%) with no significant difference in hazard ratio (HR) for death between CCC and non-ccc (HR; 1.16, 95% CI; 0.85 1.57, random-effects model). Comparing the HR based on stage I + II, and stage III + IV, between CCC and non-ccc, showed that CCC patients had a higher hazard rate for death than those with non-ccc of the ovary (stage I+ II; HR; 1.17, 95% CI; 1.01 1.36, stage III + IV; HR; 1.65, 95% CI; 1.52 1.79). In a comparison of CCC and serous EOC, advanced stage (III and IV) CCC only showed a poorer hazard rate for death than serous EOC (HR; 1.71, 95% CI; 1.57 1.86). Conclusion. This analysis suggests that ovarian CCC patients had poorer prognosis than those with other histological subtypes of EOC, especially in advanced EOC stages. Different treatment strategies may be needed for patients with ovarian CCC. 2011 Elsevier Inc. All rights reserved.
2. (complete surgical staging)? 2D very low,. 6 NRS (5 retrospective, 1 prospective study) Small study populations (<50), low qualities
3. EOC stage 1 systemic pelvic/paraaortic LND? LN sampling. ( B), systemic LND. ( 1D) 1 RCT (Maggioni A et al. 2006. 138 sys LND vs. 130 LN sampling for EOC stage I-II, OS difference (-)) + 1 NRS Systemic LND.
4. Neoadjuvant chemotherapy? E (very low) NAC extensive stage III-IV NAC, NAC 1 RCT + 3 NRS
5. IP chemotherpay first-line chemotherpy? 2A HIGH, QoL 2A 9 RCT HR 0.80 (95% CI 0.71, 0.90) IP chemotherapy
6. Dose-dense chemotherapy first-line chemotherapy? 2B 1 RCT (Katsumata N et al. 2009. PFS 28m, 3YSR 72.1%, more toxic) + 1 NRS Dose-dense chemotherapy:, GOG 262 control arm,
7. Secondary cytoreduction? 2D Optimal debulking secondary cytoreduction.. 5 NRS
8. Platinum resistant recurrent EOC combination chemotherapy? B 2E 1 RCT (topo. vs. topo+etopiside, or +gemci.) + 18 NRS (phase II single cohort)
Other Key Questions... Preop. PET/CT imaging study? LND? Paraaortic LND upper level? (IMA or Lt.renal v. or?) Staging operation midline incision? Optimal debulking, partial OM total OM? Partial OM? IP chemotherapy regimen? When can we justify the primary TC cycle more than 6? Suboptimal debulking, interval debulking? Optimal debulking adjuvant chemo. IDS? 6 resectable mass,? Platinum-free interval non-platinum agent?
Fertility-sparing surgery & comprehensive staging Complete surgical staging BOT Chemotherapy for IA or IB, G2? Chemotherapy cycles F/U inverval NAC
β Monthly paclitaxel (GOG 178, 135-175mg/m2 monthly for 12 cycles) PR IDS & postop. CTx
Combination chemotherapy Clinical trial or salvage therapy
National Comprehensive Cancer Network Guidelines v 2. 2011 EOC / FTC / PPC
Updates (1)... Extensive stage III-IV NAC, fellowship-trained GYN oncologist nonsurgical candidate... Stage II-IV disease primary chemotherapy dose-dense cisplatin IP.. - PTX 80mg/m2 IV over 1h Days 1, 8, and 15 & Carbo AUC 6 IV over 1h. - PTX 135mg/m2 IV over 24h Day 1; Cisplatin 75-100mg/m2 IP, Day 2; PTX 60mg/m2 IP Day 8 Secondary cytoreductive surgery, clinically lowvolume or focal recurrence after DFI > 6 mo., clinically low-volume or focal recurrence... Sex cord-stromal tumor complete staging LND...
Updates (2)... GOG 218 ICON7 more mature data BEV. routine. anti-angiogenesis... BRCA mutation PARP inhibitor olaparib..., clinical trial setting...
PARPi Phase II trials of olaparib in BRCA-mutated ovarian cancer showed high response rates and minimal toxicities. (ICEBERG 2, ICEBERG 3) No phase III trials of PARP inhibitors in ovarian cancer
Phase II randomized placebo-controlled study of olaparib in pts. with platinumsens. relapsed serous ov.ca (PSR SOC) J.A. Ledermann
Phase II randomized placebo-controlled study of olaparib in pts. with platinum-sens. relapsed serous ov.ca (PSR SOC) J.A. Ledermann First study demonstrating a significant PFS benefit following maintenance treatment with a PARP inhibitor for PSR SOC Olaparib improved median PFS by 3.6 months compared with placebo, following completion of chemotherapy 50% of olaparib and 16% of placebo pts. were still on treatment at the time of the anlysis
Bevacizumab incorporation into ovarian cancer treatment ICON 7 : primary setting OCEANS : platinum-sensitive recurrent setting
Result of interim analysis of OS in the GCIG ICON7 phase III randomized trial of bev. in women with newly diagnosed ovarian cancer G. Kristensen
GCIG ICON7 Bev. 7.5mg/kg 12 cycles
GOG 218 Bev. 15mg/kg 15 cycles
Bevacizumab First-line therapy, median PFS (months) GOG 218: curves together at 24 m ICON 7: curves cross at 22 m
Bevacizumab First-line therapy, median PFS (months)
Differences between GOG 218 vs ICON7 Design: 3 arm vs. 2 arm Stage III-IV vs 1(high risk)-iv Suboptimal III 65% vs 27% Dose: 15 vs 7.5 mg/kg Duration of maintenace: 15 vs 12 cycles PD definition: RECIST or CA 125 vs RECIST only
Result of interim analysis of OS in the GCIG ICON7 phase III randomized trial of bev. in women with newly diagnosed ovarian cancer G. Kristensen Continued improvement in PFS with no crossing of curves Trend for improved OS continues in the total population Treatment effect is greater in pts. at high risk of recurrence, which may be of clinical relevance Final OS results are due in 2013
OCEANS A randomized, double-blinded, placebo-controlled, phase III trial of chemo. with or without BEV in pts. with platinum-sensitive EOC, PPC, or FTC C. Aghajanian phase III AGO/NCIC/EORTC trial in platinumsensitive OC Efficacy C (n=178) CG (n=178) Median PFS 5.8m 8.6m HR for PFS 0.72 (p=0.0031) ORR 31% 47% p=0.0016 Median OS 17.3m 18.0m HR for OS 0.96 (p=0.7349)
OCEANS: study schema Platinum-sens. rec.oc Measurable ds. ECOG 0/1 No prior chemo. for rec. OC No prior BEV N=484 C AUC 4 G 1000 mg/m2, d1 & 8 C AUC 4 G 1000 mg/m2, d1 & 8 + + PL q 3w until PD BEV 15mg/kg q 3w until PD Stratification variables CG for 6 (up to 10) cycles Platinum-free interval (6-12 vs. >12m) Secondary cytoreduction (y or n)
BEV. halves Progression Risk in rec. OC
Bevacizumab New standard of care in ovarian cancer? PFS modest for all comers No OS benefit PFS for suboptimal/iv pts benefit+ Cost BEV cannot be considered the new standard of care for all patients with adv.ov.ca