VIEWS: 3 PAGES: 71 POSTED ON: 9/24/2012
DISCLAIMER This slide deck in its original and unaltered format is a certified educational activity current as of April 2010. All materials contained herein reflect the views of the faculty, and not those of IMER, the CME provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity. Usage Rights This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details. DISCLAIMER Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. DISCLOSURE OF UNLABELED USE This educational activity may contain discussion of published and investigational uses of agents that are not indicated by the FDA. IMER does not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of IMER. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. Disclosure of Conflicts of Interest Bradley J. Monk, MD, FACOG, FACS Reported a financial interest/relationship or affiliation in the form of: Speakers' Bureau, Lilly USA, GlaxoSmithKline plc., Merck & Co., Inc.; Contracted Research, Johnson & Johnson Services, Inc., GlaxoSmithKline plc., sanofi-aventis U.S. Community Oncology Clinical Debates: Ovarian Cancer Learning Objectives Upon completion of this program, participants should be better able to: Describe the role, rationale, and types of surgical interventions for initial and recurrent treatment of ovarian cancer Identify evidence-based clinical decisions incorporating standard chemotherapeutic and biologic treatment for newly diagnosed and recurrent epithelial ovarian cancer Outline recent data regarding treatment options between chemo- sensitive and chemo-resistant patients with recurrent ovarian cancer Analyze recent data evaluating angiogenesis inhibitors alone or in combination with chemotherapeutic agents for the treatment of recurrent ovarian cancer Describe the benefits and risks of therapeutic options when counseling patients on treatment planning Identify ways to counsel patients on the availability of clinical trial participation when warranted Case Study 1: Front-Line Therapy A 52-year-old insurance executive with ascites and 14-cm pelvic mass on exam and CT scan – Omental cake seen on CT as well; CA125 = 899 preoperatively Exploratory laparotomy with radical tumor debulking including TAH/BSO, omentectomy, appendectomy, lymphadenectomy Optimally cytoreduced stage IIIC papillary serous ovarian cancer PS = 0; No significant co-morbidities Question 1 Which treatment would you recommend for this patient? 1. IV carboplatin and IV paclitaxel 2. IV carboplatin and IV docetaxel 3. IP cisplatin and IV paclitaxel 4. IP cisplatin, IV paclitaxel, and IP paclitaxel 5. IV platinum and taxane plus bevacizumab Disease Burden Incidence 21,550 with mortality 14,600 75% cases present with stage III/IV Fifth leading cause of cancer deaths in females Increased incidence with increasing age Nearly 70% of advanced stage cancers relapse ACS, 2009. Survival: Increasing Over the Decades 1 SEER Data 1973–1997 0.9 N = 32,845 0.8 Proportion Surviving GOG 172 0.7 2006 0.6 1973-79 0.5 1980-89 0.4 1990-97 0.3 0.2 0.1 0 0 2 4 6 8 10 Years After Diagnosis NCI, 2009; Armstrong et al, 2006. Primary Cytoreduction Meta-analysis: 53 studies (1989–1998) – 81 cohorts (stage III/IV) – N = 6,885 patients Median Survival (mos) Results – Expert centers have high optimal rates – Optimal vs not: 11 mos (50% increase) – Each 10% in cytoreduction = 5.5% in % Cytoreduction survival – Platinum intensity = NS Bristow et al, 2002. First-Line Therapy Surgery with comprehensive staging or maximal cytoreduction Platinum + taxane chemotherapy (carboplatin + paclitaxel) ? ? Maintenance IP (opt) Biologics Herzog et al, 2006, Herzog, 2006. GOG 182: Randomized 5-Arm Trial for Epithelial, Ovarian, and Primary Peritoneal Cancer Paclitaxel 175 mg/m2 IV (3H) D1 x 8 cycles (q 21 days) I Carboplatin AUC 6 IV D1 STRATIFICATION No gross residual Paclitaxel 175 mg/m2 IV (3H) D1 x 8 cycles (q 21 days) vs macroscopic Dz Carboplatin AUC 5 IV D1 vs macroscopic Dz II Gemcitabine 800 mg/m2/d IV D1, 8 and intent for interval cytoreduction Paclitaxel 175 mg/m2 IV (3H) D1 x 8 cycles (q 21 days) III Carboplatin AUC 5 IV D1 RANDOMIZATION Doxil 30 mg/m2/d IV (every other) D1 Stage III/IV opt or subopt Carboplatin AUC 5 IV D3 Paclitaxel 175 mg/m2 IV (3H) Primary end points: Carboplatin AUC 6 IV PFS/OS/RR IV Topotecan 1.25 mg/m2/d IV D1–3 x 4 cycles (q 21 days) x 4 cycles (q 21 days) Carboplatin AUC 6 IV D8 Paclitaxel 175 mg/m2 IV (3H) Carboplatin AUC 6 IV V Gemcitabine 800 mg/m2/d IV D1, 8 x 4 cycles (q 21 days) x 4 cycles (q 21 days) Copeland et al, 2003. GOG 182-ICON5: Overall Survival Median OS and HR (95% CI) 40.0 1.000 40.4 0.978 (0.838-1.141) 42.8 0.972 (0.832-1.136) 39.1 1.068 (0.918-1.244) 40.2 1.035 (0.888-1.206) Key Phase III Studies 1996 2003 2006 GOG 111 GOG 158 GOG 172 Study Comparison Results first-line paclitaxel ↑ PFS cisplatin/cyclophosphami GOG 111 and OS in advanced de vs cisplatin/paclitaxel disease carboplatin/paclitaxel cisplatin/paclitaxel GOG 158 non-inferior to vs carboplatin/paclitaxel cisplatin/paclitaxel paclitaxel + IV cisplatin vs paclitaxel + IP arm ↑ OS in optimally GOG 172 IP cisplatin + IP debulked stage III disease paclitaxel McGuire et al, 1996; Ozols et al, 2003; Armstrong et al, 2006. Primary Treatment Guidelines • Grade 1: Observe • Grade 2: Observe or carboplatin/paclitaxel Stage IA or IB x 3–6 • Grade 3: Carboplatin/paclitaxel x 3–6 • Grade 1–3: Carboplatin/paclitaxel x 3–6 Stage IC • Intraperitoneal chemotherapya Stage II–IV • Carboplatin/paclitaxel x 6–8 • Completion surgery aOptimally debulked stage III disease. NCCN, 2009. Treatment Paradigm Diagnosis Evaluation Progression Evaluation Progression Death Symptoms Chemo #1 +/- Consolidation Chemo #2 Chemo #3+ Cure Staging Supportive Care Herzog, 2006. Historic Paradigm of Recurrent Disease Platinum Platinum refractory/resistant sensitive PFI < 6 mos PFI > 6 mos Non-platinum Platinuma treatment retreatment Increasing evidence suggests the duration of the PFI also influences outcomes of non-platinum chemotherapeutic agents/regimens aAlthough platinum retreatment was the traditional therapy, emerging evidence suggests non-platinum doublets are effective in treating platinum-sensitive recurrent disease. Monk et al, 2009. Controversies in Ovarian Cancer Screening Maintenance therapy Optimal chemotherapy, CA125 association with schedule, courses, and response and progression end points Treating to progression Role of biologics Defining and detecting IP therapy standard relapse Moss et al, 2002. Debate 1 IP Chemotherapy Should Be the Standard for Optimally Cytoreduced Patients in Front-Line Ovarian Cancer IP Chemotherapy Median PFS Median OS HR HR (mos) (mos) IV IP IV IP GOG 0.76 – – – 41 49 104 (p = .02) GOG 0.78 0.81 22 28 52 63 114 (p = .01) (p = .05) GOG 0.80 0.75 172 18 24 50 66 (p = .05) (p = .03) Alberts et al, 1996; Markman et al, 2001; Armstrong et al, 2006. Ovarian Cancer: IP Chemotherapy Primary end point: PFS Need 208 events to detect 50% increase in PFS 417 randomized; 213 events US NIH, 2009a. GOG 172 Treatment Regimens Every 21 Days x 6 Regimen 1 D1: IV Paclitaxel 135 mg/m2/24h IV D2: IV Cisplatin 75 mg/m2 D1 D2 IV IV Regimen 2 D1: IV Paclitaxel 135 mg/m2/24h IP D2: IP Cisplatin 100 mg/m2 D8: IP Paclitaxel 60 mg/m2 D1 D2 D8 IV IP IP Armstrong et al, 2006, 2002. GOG 172 Survival PFS OS 1.0 1.0 0.9 Rx Group PF Failed Total IV 50 160 210 0.9 Proportion Progression Free (%) 0.8 IP 63 142 205 0.8 0.7 IV: 18 mos 0.7 0.6 IP: 24 mos 0.6 HR: 0.80, p = .05 0.5 0.5 IV: 50 mos 0.4 IP: 66 mos 0.4 HR: 0.75, p = .03 0.3 0.3 0.2 0.2 Rx Group Alive Dead Total 0.1 IV 93 117 210 0.1 IP 117 88 205 0.0 0.0 0 12 24 36 48 60 0 12 24 36 48 60 Time (mos on study) Time (mos on study) Armstrong et al, 2006. GOG 172 Non-Hematologic Toxicity Grade 3/4 AEs IV (%) IP (%) Gastrointestinal event 24 46 Renal or 2 7 genitourinary event Fatigue 4 18 Pain 1 11 Metabolic event 7 27 Neurologic event 9 19 Armstrong et al, 2006. GOG 172 Number of IP Courses Completed 100 90 92 80 70 74 % Completed 60 50 59 52 47 40 42 30 20 10 8 0 0 1 2 3 4 5 6 IP Courses Walker et al, 2006. IP: Pro and Con? Supporting Rationale Challenging Rationale Three phase III trials show Toxicity improved PFS/OS High discontinuation rate Tolerable in selected patients Lack of standardized regimen Regimen may be modifiable to decrease toxicity Lack of comparison to contemporary control arm GOG 172 with outstanding median survival of 66 mos Majority of studies administered higher doses in IP arm thus limited direct comparison to IV Markman et al, 1999. Debate 2 Maintenance Should Be Administered to Complete Clinical Responders in Front-Line Ovarian Cancer Consolidation Therapy: GOG 178 R Paclitaxel (3-hour) 175 mg/m2 q 28 d x 3 A EOC, fallopian, PP N Stage III/IV Prior chemo 5–6 cycles D Register 3–8 weeks O CCR Neuropathy ≤ grade II M I Paclitaxel (3-hour) Z 175 mg/m2 q 28 d x 12 E N = 450 anticipated Accrual closed 9/6/2001 End points N = 277; 222 with follow-up • PFS 54 progression events • OS Markman et al, 2003. GOG 178: Consolidation Unadjusted Log Rank p (one-sided) = .0035 Adjusted Log Rank p (one-sided) = .0023 Markman et al, 2003. GCIG Intergroup Protocol: GINECO Paclitaxel (3-hour) R 175 mg/m2 q 21 d x 6 A Carboplatin French/German Study AUC = 5.0 q 21 d x 6 N Group D EOC (Stage IIB–IV) O All Strata M I Paclitaxel (3-hour) 175 mg/m2 q 21 d x 6 N = 1,308 Z Carboplatin E AUC = 5.0 q 21 d x 6 Topotecan 1.25 mg/m2 q 21 d x 4 Pfisterer, 1999. Maintenance Therapy: GOG Trial R Observation A EOC, fallopian, PP N Stage III/IV D Prior chemo 5–8 cycles Paclitaxel (3-hour) Register 3–8 weeks O 135 mg/m2 q 28 d x 12 CCR M Neuropathy ≤ grade II I Z PG-Ptx (paclitaxel poliglumex) E 135 mg/m2 q 28 d x 12 End points N = 1,400 anticipated • PFS Phase III; Superiority Design • OS US NIH, 2008. Ovarian Cancer: First-Line Sorafenib Maintenance (Phase II Study) Sorafenib 400 mg BID 1:1 Primary: Randomization PFS Placebo Continue until progression Primary end point: PFS (defined as time from randomization to disease progression or death) Control median PFS: 20 mos 1-sided alpha of 0.1 Power – 90% for 67% increase in PFS – 78% for 50% increase in PFS No of events: 101 No of patients: 217 Threshold for achieving p < .1 (SoE 0.5): ~ 30% increase in PFS US NIH, 2009b. Maintenance: Pro and Con? Supporting Rationale Challenging Rationale Theoretical basis Additional toxicity Majority will recur without Lack of proven survival treatment advantage Generally tolerable Cost GOG 178 with PFS Inconvenience and stress improvement for patient Clinical trials open GOG 212 under enrolled Herzog et al, 2006. Debate 3 Biologics Should Be Incorporated Into Front-Line Ovarian Cancer Treatment Biologics as Maintenance: Anti-VEGF Agents Target Class Agents Ligand VEGF-A Maba Bevacizumab VEGF Soluble decoy receptor VEGF trap Receptor VEGFR TKIb Cediranib VEGFR TKIb Pazopanib VEGFR + PDGFR + Raf-K Sorafenib VEGFR + PDGFR TKIb Sunitinib VEGFR + PDGFR TKIb Motesanib VEGFR2 Maba Ramucirumab aMab. bTKI. Presta et al, 1997; Holash et al, 2002; Hu et al, 2005. GOG 218 Paclitaxel (3 hours) Placebo 175 mg/m2 q 21 d x 6 D1 q 21d Carboplatin x 15 mos AUC = 6 q 21 d x 6 R Placebo D1 x 5, start Cycle 2 A EOC N Paclitaxel (3 hours) 1 periton D 175 mg/m2 q 21 d x 6 Placebo St III/IV Carboplatin D1 q 21d O AUC = 6 q 21 d x 6 Subopt x 15 mos M Bev D1 x 5, start Cycle 2 I Z Paclitaxel (3 hours) Bev 175 mg/m2 q 21 d x 6 E Carboplatin D1 q 21d AUC = 6 q 21 d x 6 x 15 mos Bev D1 x 5, start Cycle 2 Bevacizumab 15 mg/kg IV Burger, 2007. Front-Line Trial: GCIG ICON-7 EOC, PP cancer Paclitaxel Paclitaxel Carboplatin Carboplatin Placebo Bevacizumab Clinic Assessment Bevacizumab x 12 cycles N = 500 patients US NIH, 2009c. Biologics Front-Line: Pro and Con Supporting Rationale Challenging Rationale Theoretically appealing Additional overall toxicity Different and perhaps less Some unique severe toxicities toxicity Cost Generally tolerable Patient selection GOG 170-D with proven efficacy in recurrent Lack of proven survival advantage Clinical trials open Lack of understanding of long- Combinable with term effects chemotherapy Opportunity for PO administration Recurrent Disease Case Study 2: Recurrent Disease A 68-year-old originally with stage IV ovarian cancer with positive small pleural effusion optimally cytoreduced who was then treated on GOG 218 (carb/Ptx +/- bev) CA125 initially = 456 and nadirs at 11 She had residual grade 1 neuropathy and has mild hypertension; PS = 0 Optimally cytoreduced stage IIIC papillary serous ovarian cancer 9 mos later her CA125 = 37, with repeat 1 mos later = 118; CT with small volume multifocal disease Question 2 Is she plat sensitive or resistant? Which treatment would you recommend? 1. Carboplatin/paclitaxel 2. Carboplatin/gemcitabine 3. Pegylated liposomal doxorubicin 4. Topotecan 5. Weekly taxane 6. Plat-based doublet plus bevacizumab 7. Pegylated Liposomal doxorubicin and carboplatin 8. Other Considerations in Recurrence Drug Patient Tumor Efficacy Symptoms TFI Co-morbidities Schedule Resistance status Performance status Toxicity Resistance mechanisms Disease volume Prior toxicity Recurrence Therapy RR (%) Drug Platinum-Resistant Platinum-Sensitive Docetaxel Doxorubicin Hcl liposome injection Etoposide Gemcitabinea Hexamethylmelamine 10%–20% 20%–35% Paclitaxel Platinum Topotecan Vinorelbine FDA approved aWithcarboplatin. Herzog, 2006. Recurrence Rx Options Liposomal doxorubicin Novel taxanes (nab-paclitaxel, Topotecan CT-2103) Gemcitabine Novel platinum analogs Taxane retreatment (bolus, Combination therapy or weekly) retreatment Docetaxel Monoclonals/anti-angiogenics VP-16 Other targeted biologics Vinorelbine Stem cell, high-dose Platinum retreatment Gene therapy Historical agents Hormones (tamoxifen, letrozole) – Ifosfamide – Melphalan – Hexamethylmelamine – 5-FU/leucovorin Berek, 2005. NCCN Guidelines for Persistent or Recurrent Epithelial Ovarian Cancer Progression or stable disease on primary chemotherapy or Supportive care Complete remission and relapse or <6 mo after stopping chemotherapy Recurrence regimen Stage II, III and IV with partial response including positive Recurrence chemotherapy reassessment surgical procedure or (second look; including microscopic disease) Observe (category 2B) Carboplatin/paclitaxel Complete remission and relapse >6 mo (category 1) after stopping chemotherapy Or Gemcitabine/carboplatin Recurrence regimen Clinically low-volume or focal recurrence Consider secondary after disease-free interval >6 mo cytoreductive surgery And/or Recurrence chemotherapy Concept of Platinum Sensitivity 0 mos 6 mos 12 mos Primary treatment Refractory Resistant Platinum sensitive End of front-line therapy Herzog, 2006. Platinum Refractory GOG Trials Resistant GOG Treatment RR (%) Population 126-H 25 Topotecan (24H) 4 126-J 60 Docetaxela 22 126-K 25 Oxaliplatin 4 126-L 57 Gemcitabine + paclitaxel 16 126-M 50 Ixabepilone 14 126-N 48 Weekly paclitaxela 21 126-Q 51 Pemetrexeda 20 aAfter paclitaxel. Rose et al, 2003; Markman et al, 2006, 1999; Miller et al, 2009; Fracasso et al, 2003; Brewer et al, 2006. Debate 4 Treatment to Progression Is Best Practice in Recurrent Ovarian Cancer Value of Stable Disease: Relapsed Ovarian Cancer N = 392 Cesano et al, 1999. Treating to Progression: Pro and Con Supporting Rationale Challenging Rationale Symptom palliation Cumulative toxicities Maintains stable disease Negative impact on QOL and psychosocial issues Fewer cumulative toxicities with many of Use of more effective the novel agents agents delayed Limited number of Limited documented options benefits Survival advantage Debate 5 Biologics Should Be Incorporated Into Recurrent Ovarian Cancer Treatment NCCN 2009 Acceptable Recurrence Therapies Agents Cytotoxic Therapy Hormonal Targeted Radiation Therapy Therapy Therapy NCCN preferred Platinum sensitive combinations Bevacizumab Carbo/paclitaxel (cat 1) Carbo/docetaxel Carbo/gemcitabine Cisplatin/gemcitabine Platinum sensitive monotherapy Carboplatin Cisplatin Platinum resistant single agents Docetaxel Etoposide (oral) Gemcitabine Liposomal doxorubicin Paclitaxel, weekly Pemetrexed Topotecan Other acceptable Altretamine Anastrozole Palliative and potential agents Capecitabine Letrozole localized Cyclophosphamide Leuprolide radiation Ifosfamide Megestrol therapy Irinotecan acetate Melphalan Tamoxifen Oxaliplatin Paclitaxel Vinorelbine NCCN, 2009. GOG 160/170 Series: Performance Comparison Bevacizumab PFS ≥ 6 (%) Sorafenib Imatinib Gefitinib Trastuzumab Lapatinib Vorinostat RR (%) US NIH, 2009d. GOG 0213 Trial US NIH, 2009e. Phase III Study of Carboplatin + Gemcitabine ± Bevacizumab in Patients With Platinum- Sensitive Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Oceans Trial Gemcitabine 1,000 mg/m2 Days 1 + 8 BV BV Carboplatin AUC 4 Day 1 (to 51 to PD Bevacizumab 15 mg/kg Day 1 q 21 days x 6a wks) R Gemcitabine 1,000 mg/m2 Days 1 + 8 Placebo Carboplatin AUC 4 Day 1 Placebo IV Day 1 q 21 days x 6 (to 51 wks) Unblind aUpto 10 cycles allowed. US NIH, 2009f. Biologics in the Recurrent Setting ET-743 (Ecteinascidin) Taxanes (ABI-007, CTI-2103) Epothilones (patupilone, ixabepilone) Karenitecin Phenoxodiol Folate (pemetrexed, farletuzumab) Abagovomab Biologics: Multiple addressing VEGFR or EGFR pathways Biologics Front-Line: Pro and Con Supporting Rationale Challenging Rationale Theoretically appealing Additional overall toxicity Different toxicities Some unique severe toxicities Generally tolerable Cost GOG 170-D with proven efficacy in recurrent How long to continue? Clinical trials open Lack of proven OS advantage Need novel agents to improve survival Ascites palliation Benefits of Participation Clinical trials that are well-designed and well- executed are the best approach for eligible participants to: – Play an active role in their own healthcare – Gain access to new research treatments before they are widely available – Obtain expert medical care at leading health care facilities during the trial – Help others by contributing to medical research US NIH, 2007. Debate 6 CA125 Values Should Be Monitored Routinely to Detect Recurrent Ovarian Cancer Trial Profile Registered patients N = 1,442 Non-randomised patients N (%) 421 (29) CA125 < 2 ULN and no relapse at trial closure 61 (4) Simultaneous relapse and CA125 > 2 ULN 213 (15) Relapsed without CA125 > 2 ULN 56 (4) Died 133 (9) Patient withdrawal 29 (2) Other/unknown reasons Randomized N = 529 (37%) Early treatment Delayed treatment N = 265 N = 264 N = 254 (96%) started second-line N = 233 (88%) started second-line chemotherapy chemotherapy Rustin, 2009. Time From Randomisation to Second-Line Chemotherapy 1.00 Median (mos) Second-Line Chemotherapy (%) Proportion Alive Not Started Early 0.8 0.75 Delayed 5.6 HR = 0.29 (95% CI 0.24, 0.35) p < .00001 0.50 0.25 0.00 0 3 6 9 12 15 18 21 24 Time (mos since randomisation) Number at risk Early 265 23 16 14 11 11 10 10 9 Delayed 264 177 116 91 69 56 49 42 33 Rustin, 2009. Overall Survival HR = 1.00 (95% CI 0.82–1.22) p = .98 1.00 Abs diff at 2 years = -0.1% (95% CI diff = -6.8, 6.3%) Proportion Surviving (%) 0.75 Early Delayed 0.50 0.25 0.00 0 6 12 18 24 30 36 42 48 54 60 Time (mos since randomisation) Number at risk Early 265 247 211 165 131 94 72 51 38 31 22 Delayed 264 236 203 167 129 103 69 53 38 31 19 Rustin, 2009. SGO Statement on Use of CA125 for Monitoring Ovarian Cancer Role of secondary cytoreduction not addressed Not stratified for residual disease after cytoreduction Remission not confirmed by imaging Treatment at relapse not standardized “Patients and their physicians should still have the opportunity to choose [CA125 monitoring] as a philosophy of active management that includes participation in trials of novel therapies.” SGO, 2009. CA125 Monitoring: Pro and Con Supporting Rationale Challenging Rationale Avoid symptom onset Leads to increased toxicity Patient demand Negative impact on QOL and psychosocial issues “Active” surveillance strategy Lack of survival advantage Avoid routine radiography Cost Rustin data may not be Phase III data shows no applicable to US population survival advantage Debate 7 Secondary Cytoreduction Should Be Routinely Offered to Recurrent Ovarian Cancer Patients Secondary Cytoreduction Tumor Mass Controversial Inconsistent definitions Vena Cava Benefit appears Renal Vein confined to patients like to respond to Kidney additional chemo – > 12-mos PFI Diaphragm Resected Liver – Isolated site of recurrence – Disease completely resectable Kidney PIM & IMPACt Inc., 2009. Secondary Cytoreduction: Survival by Postoperative Residuum Fader et al, 2007. Secondary Debulking: Candidate Selection Secondary Cytoreduction: Pro and Con Supporting Rationale Challenging Rationale Theoretical appeal Morbidity Survival advantage in Negative impact on QOL selected patients Lack of clear survival “Active” approach advantage Newer tools for patient Cost selection available Patient selection difficult Key Takeaways Front-line surgical therapy should consist of adequate and complete staging with optimal cytoreduction as indicated Standard front-line chemotherapy should contain a platinum and a taxane Novel chemotherapeutics and targeted biologics provide multiple options for adjuvant therapy Treatment selection for relapsed ovarian cancer must be based on patient specific variables with the goal of extending survival and maximizing QOL
"GOG IMER Institute for Medical Education Research"