Late recurrent epithelial ovarian cancer

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1 Late recurrent epithelial ovarian cancer Dominic Richards University of Cape Town and New Somerset Hospital Gynaecological Oncology Unit September 2016

2 LATE RECURRENT EPITHELIAL OVARIAN CANCER Background Surveillance Chemotherapy Targeted therapies Secondary cyto-reductive surgery Conclusion

3 BACKGROUND Recurrence > 6 months following completion of primary treatment Advanced stage: 70% recurrence rate Stage I & II: 20 25% recurrence rate LETHAL A heterogeneous group, no single optimal treatment modality Treatment goals Cure is off the table Symptom relief Improve and prolong QoL Prolong PFI

4 SURVEILLANCE Biochemical: tumour markers, often CA 125 Doubling of baseline may achieve early detection before a clinical relapse Earlier introduction of chemotherapy Tumour-marker anxiety Early intervention DOES NOT translate into increased survival Early intervention DOES lead to impaired QoL Radiological CT, MRI, FDG-PET Risks of radiation exposure, especially with regular studies Expensive DOES NOT translate into increased survival Clinical

5 CHEMOTHERAPY: Platinum sensitivity Essential to define Prolonged initial PFI equals better response to second-line chemo Platinum resistant disease 5 25% response rate msr of 1 year Platinum sensitive disease up to 75% response rate msr of 3 years

6 CHEMOTHERAPY IN LATE RECURRENT E. O. C. PLATINUM SENSITIVE DISEASE Platinum always contained in second-line chemotherapy Almost always given as combination chemotherapy Paclitaxel Gemcitabine Pegylated liposomal doxorubicin (CAELYX) Combination chemotherapy better PFI vs. QoL and toxicities No one combination is overwhelmingly better Recurrent use of platinum leads to resistance

7 CHEMOTHERAPY CALYPSO trial GCIG 259 participants Two-arms Carbo-CAELYX Carbo-paclitaxel (CP) Equal response rates No difference in PFS or OS Higher toxicities in CP arm

8 ANGIOGENESIS INHIBITORS Why? Ever shortening duration of response after chemotherapy. Bevacizumab (Avastin ) & Cediranib (Recentin ) AURELIA trial Platinum resistant disease Randomised Phase III NP-Chemo + Bev vs. NP-Chemo alone mpfs 6.8 vs. 3.4 m OCEANS trial Platinum sensitive disease CG + Bev + Bev(maint) vs. CG + Placebo + Placebo(maint) No significant difference in OS PFS 12.4 m vs. 8.4 m Hypertension and spontaneous visceral perforations in the Bev group

9 ANGIOGENESIS INHIBITORS ARM Platinum + placebo + placebo (m) Platinum + cediranib + placebo (m) Platinum + cediranib + cediranib (m) Progression at 19.5 months mpfs (months) 96% % % 11 ICON 6 CEDIRANIB Phase III RCT patients Platinum sensitive disease 19.5 month follow-up Trial issues - drug manufacture 32 vs. 10% discontinuation rates in cediranib arms Diarrhoea, voice changes, neutropenia

10 PARP inhibitors N Eng J Med 2012 Olaparib maintenance therapy in platinum sensitive ROC Monotherapy Olaparib vs. placebo PFS 8.4 vs. 4.8 months (p<0.001) Toxicities mild, 10% in O group No difference in OS Lancet 2015 Olaparib in combination with chemotherapy, and maintenance therapy CP + O + O(maint) vs. CP only PFS 12.2 vs 9.6 m Minor toxicities in the CP+O+O Greater PFS in BRCA carriers

11 LANCET 2015: Olaparib in ROC BRCA +

12 SURGERY Optimal SCS debulking rates 11 81% Mortality of SCS 0 5.5% Is there good evidence for secondary cyto-reductive surgery for R.E.O.C? There are NO randomised prospective data. COCHRANE non-randomised studies 1194 women Significant increase in OS in women with platinum-sensitive ROC and CR

13 SURGERY: Level 1 evidence awaited German study 1 st recurrence Platinum sensitive ECOG 0 CR at primary surgery No ascites Experimental: SCS plus chemo Control: Chemo Chemo: CP, CG, CPLD

14 SURGERY: Level 1 evidence awaited Dutch Study Surgery for Ovarian Cancer Recurrence Similar inclusion criteria to DESKTOP III Experimental: SCS plus 6 cycles platinum-based chemo Control: 6 cycles platinum-based chemo Primary outcome = PFS

15 Patient selection for SCS AGO/DESKTOP I TIAN MODEL Complete resection at primary operation ECOG 0 Ascites < 500 ml If all three attained, 76% CR rate Low score: High score: 53 83% CR 20 42% CR

16 SCS: laparoscopic assessment Standard management in some institutions No RCT yet Still surgery - with associated risks LapOvCa study Primary disease Outcome = CR Extrapolation to SCS

17 CONCLUSION EOC: a chronic disease with high relapse rates Recurrent EOC is lethal Platinum sensitivity and long primary PFI are paramount Retrospective data has shown SCS with CR plus chemotherapy has better outcomes and longer PFI DESKTOP III and SOCceR results eagerly awaited Treatment must be individualised Don t be a Surgical Cowboy! To cure sometimes, to relieve often and to comfort always. Hippocrates