TREATMENT FOR RELAPSING PLATINUM SENSITIVE EPITHELIAL

Sandro Pignata, MD, PhD Sabrina Chiara Cecere, MD Uro-Gynecological Department, Division of Medical Oncology, IRCCS National Cancer Institute “Fondazione G. Pascale”, Naples, Italy OVARIAN CANCER (OC) RELAPSE

Despite the best upfront treatment, ovarian cancer has a high incidence of relapse

About 70–80% of FIGO stage III-IV ovarian cancer patients develop a disease relapse within 5 years

Yang JC, et al. N Engl J Med. 2003; 349:427-34. Adapted from: Piccart MJ, et al. Randomised Intergroup Trial of – Versus Cisplatin– in Women With Advanced Epithelial Ovarian Cancer: Three-Year Results, J Natl Cancer Inst, 2000, 92, 9 , 699–708, by permission of Oxford University Press RECURRENT OVARIAN CANCER (ROC): POPULATION CHARACTERISTICS

Response to Platinum Response to Time to Recurrence Further Platinum Platinum-sensitive 12 mos 30-60% Platinum-partially sensitive 6-12 mos 25-30% Platinum-resistant <6 mos <10% Platinum-refractory No initial response N/A THE PLATINUM-FREE INTERVAL (PFI) TO CLASSIFY OC RELAPSE Breaking the old and arbitrary categorisation of relapsed OC

P 0 3 6 12 18 24 months R I M A Refractory R Y Resistant T H E Partially Sensitive R A P Y Fully Sensitive

Pisano C, et al. Ther Clin Risk Manag. 2009;5:421-426; Gadducci A, et al. Anticancer Res. 2001;21:3525-3533. THE PLATINUM-FREE INTERVAL (PFI) TO CLASSIFY OC RELAPSE Breaking the old and arbitrary categorisation of relapsed OC

1000 100 Overall survival

800 80

600 60 Response rate 366 400 40

PFS Survival(days)

Response(%) rate 217 32 200 20 9 166 90 0 0–3/Pr 0–3 3–6 6–9 9–12 12–18 ≥18 TFI (months) Platinum sensitivity is a continous variable

Adapted from Pujade-Lauraine E, et al. Proc Am Soc Clin Oncol. 2002;21: Abstract 829. PFI IS NOT THE ONLY FACTOR TO CONSIDER IN THE TREATMENT CHOICE

Fifth Ovarian Cancer Consensus Conference of the Gynaecologic Cancer InterGroup: recurrent disease

Wilson MK, et al. Ann Oncol 2017;2(4):727–32 From the Tokyo GCIG OC consensus conference…

 PFI revisited

 Treatment-free Interval (TFI) vs. Platinum-free Interval (PFI)

Leary AF, et al. Ann Oncol. 2017 Apr 1;28(4):718-726. «ONE SIZE DOSE DOES NOT FIT ALL» Breaking the old and arbitrary categorisation of relapsed OC

Tumour • Comorbidities • Surgery • Performance status • Previous treatments (type, • Residual toxicities • Histology number) • Symptoms • Molecular • Target maintenance therapy • gBRCA characterisation • TFI • sBRCA • Availability of treatments • HRD status (?) Patient Treatment Fifth Ovarian Cancer Consensus Conference of the Gynaecologic Cancer InterGroup: recurrent disease

Wilson MK, et al. Ann Oncol 2017;2(4):727–32 What has to be considered for platinum-sensitive relapse:

 Is there a role for surgery at relapse?

 Is a platinum-based therapy an option? Fifth Ovarian Cancer Consensus Conference of the Gynaecologic Cancer InterGroup: recurrent disease

Wilson MK, et al. Ann Oncol 2017;2(4):727–32 What has to be considered for platinum-sensitive relapse:

 The role of surgery at relapse

 Non platinum-based therapy as an option

 Platinum-based therapy as an option PLATINUM-SENSITIVE OC RELAPSE

AGO DESKTOP III (ENGOT-ov20; NCT01166737): Surgery at relapse

Study Design

 80 centres in Cytoreductive surgery with max. Platinum-based combination 12 countries Patients with: effort for complete resection therapy strongly recommended st  Recruitment  1 relapse R n=408 9/2010 – 3/2015  PSROC Immediate platinum-based OP  AGO Score +ve  407 of 409 pts No OP combination therapy allowed evaluated strongly recommended 3rd line (2 screening failures) PFS by Surgical Outcome

Median PFS ΔPFS HR P-value (mos) (mos) (95% CI) Wald-test No surgery 14.0 - 1 - Surgery but with 0.98 13.7 -0.3 0.8952 residual tumour (0.71-1.35) Surgery with complete 0.56 21.2 +7.2 <0.0001 resection (0.43-0.72)

du Bois A, et al. J Clin Oncol 35, 2017 (suppl; abstract 5501). Presented at ASCO Annual Meeting 2017. Courtesy of Prof A. du Bois. PLATINUM-SENSITIVE OC RELAPSE

Surgery at relapse: The new reality GOG-0213 trial design

Surgical candidate Regimen I AUC 5 YES N=107 Surgery Paclitaxel 175 mg/m2 Women with q 21 days recurrent ovarian, peritoneal primary or fallopian tube R R n=674 cancer and a Maintenance Regimen II treatment free Bevacizumab 15 mg/kg Carboplatin AUC 5 interval ≥6 months q 21 days until NO N=567 No surgery Paclitaxel 175 mg/m2 progression or toxicity Bevacizumab 15 mg/kg precludes further q 21 days treatment

Coleman L, et al. J Clin Oncol 36, 2018 (suppl; abstr 5501). Presented at ASCO Annual Meeting 2018. PLATINUM-SENSITIVE OC RELAPSE

Surgery at relapse: The new reality

Coleman L, et al. J Clin Oncol 36, 2018 (suppl; abstr 5501). Presented at ASCO Annual Meeting 2018. Courtesy of Prof L. Coleman. Fifth Ovarian Cancer Consensus Conference of the Gynaecologic Cancer InterGroup: recurrent disease

Wilson MK, et al. Ann Oncol 2017;2(4):727–32 What has to be considered for platinum-sensitive relapse:

 The role of surgery at relapse

 Non platinum-based therapy as an option

 Platinum-based therapy as an option WHEN PLATINUM IS NOT AN OPTION

• Platinum hypersensitivity • Progressed or relapsed OC during last platinum • Residual toxicity (e.g. neurotoxicity,…)

Wilson MK, et al. Ann Oncol 2017;2(4):727–32 WHEN PLATINUM IS NOT AN OPTION Hypersensitivity, incidence and development

• Incidence seems to be correlated with increased number of cycles of carboplatin administered, occurring in less than 1% of the patients during primary treatment but in 8–44% of patients during 2nd or 3rd line1,2 • The risk of hypersensitivity reactions rises with a longer platinum-free interval3 • Particular caution is advised in patients receiving:4

 More than eight courses of carboplatin

 Second platinum dose after reintroduction in second-line

1. Sliesoraitis S, Chikhale PJ. Int J Gynecol Cancer. 2005;15:13-8; 2. Gadducci A, et al. Int J Gynecol Cancer. 2008;18(4):615-20; 3. O´Cearbhaill R, et al. Gynecol Oncol. 2011;116(3):326-31; 4. Markman M, et al. J Clin Oncol.1999;17(4):1141-5. WHEN PLATINUM IS NOT AN OPTION: TFIP 6–12 MONTHS OVA-301 trial

An open-label, multi-centre, randomised Phase 3 study comparing the combination of PLD and with PLD alone in patients with advanced relapsed ovarian cancer (ROC) PFS1 OS2,3

1. Poveda A, et al. Ann Oncol 2011;22(1):39–48, by permission of Oxford University Press on behalf of the European Society for Medical Oncology (ESMO) ; 2. Reprinted from Eur J Cancer, 2012; 48, Monk BJ, et al. Trabectedin plus pegylated liposomal (PLD) versus PLD in recurrent ovarian cancer: Overall survival analysis, 2361–8; Copyright 2012, with permission from Elsevier. 3. Poveda A, et al. Cancer Treat Rev 2014;40:366–75. WHEN PLATINUM IS NOT AN OPTION The post hoc analysis of the OVA-301 trial: TFIP 6-12 months T+PLD a valid option in BRCA mutated ROC

BRCA1-mutated patients treated with T+PLD showed longer PFS and OS compared to PLD

BRCA1mut may predict improved outcome to T + PLD treatment

Monk BJ, et al. Effect of BRCA1 and XPG mutations on treatment response to trabectedin and pegylated liposomal doxorubicin in patients with advanced ovarian cancer: exploratory analysis of the phase 3 OVA-301 study. Ann Oncol 2015;26(5):914–20. by permission of Oxford University Press on behalf of The European Society for Medical Oncology (ESMO). Fifth Ovarian Cancer Consensus Conference of the Gynaecologic Cancer InterGroup: recurrent disease

Wilson MK, et al. Ann Oncol 2017;2(4):727–32 What has to be considered for platinum-sensitive relapse:

 The role of surgery at relapse

 Non platinum-based therapy as an option

 Platinum-based therapy as an option WHEN PLATINUM IS AN OPTION

 Platinum-based combination

 Platinum-based combination  PARP inhibitors

 Carboplatin + + bevacizumab  bevacizumab maintenance (for bevacizumab naïve)

 Platinum-based combination + bevacizumab  bevacizumab maintenance (for bevacizumab pre-treated in first line) WHEN PLATINUM IS AN OPTION

 Platinum-based combination

 Platinum-based combination  PARP inhibitors

 Carboplatin + gemcitabine + bevacizumab  bevacizumab maintenance (for bevacizumab naïve)

 Platinum-based combination + bevacizumab  bevacizumab maintenance (for bevacizumab pre-treated in first line) WHEN PLATINUM IS AN OPTION

All the platinum based combinations are equivalent in terms of efficacy, with different toxicity profiles

ICON 4/AGO OV 2.2 – CARBO AUC5 + TAX 175 mg/m² q21d GEICO 0104

Alopecia, neurotoxicity, haematologic toxicity, hypersensibility

CARBO AUC4 d1+ GEM 1000 mg/m² AGO OV 2.5 d1,8 q21d

Haematologic toxicity, hypersensibility

CALYPSO/ AGO OV 2.9 CARBO AUC5 + PLD 30 mg/m²

Palmoplantar erythrodysesthesia, mucositis, thrombocytopenia META-ANALYSIS COMBINATION THERAPY VS. MONOTHERAPY Carbo/paclitaxel, carbo/PLD, carbo/gemcitabine

Endpoint Odds ratio combo/mono (95% CI) P value ORR (n=1730, 8 studies) 1.42 (1.1601.74) 0.001 PFS at 2 years (n=2234, 7 studies) 0.67 (0.52-0.89) 0.004 PFS at 1 year 0.69 (0.57-0.84) 0.000 OS at 2 years (n=2315, 8 studies) 0.80 (0.067-0.95) 0.012*

Combination chemotherapy appears to improve ORR, PFS, and OS when compared to monotherapy in the management of ROC

Orlando M, et al. ASCO 2007, Abstract 5524; Pfisterer J, et al. J Clin Oncol. 24: 4699-4707, 2006; Parmar MK, et al. Lancet 361: 2099-2106, 2003. WHEN PLATINUM IS AN OPTION

 Platinum-based combination

 Platinum-based combination  PARP inhibitors

 Carboplatin + Gemcitabine + bevacizumab  bevacizumab maintenance (for bevacizumab naïve)

 platinum-based combination + bevacizumab  bevacizumab maintenance (for bevacizumab pre-treated in first line) SOLO2/ENGOT-OV21: STUDY DESIGN

Patients

 BRCA1/2 mutation tablets

 Platinum-sensitive relapsed 300 mg bid n=196 Primary endpoint ovarian cancer R 2:1 Investigator-assessed  At least 2 prior lines of PFS platinum therapy Placebo

 CR or PR to most recent n=99 platinum therapy

Sensitivity analysis: PFS by blinded independent central review (BICR) Key secondary endpoints:

 Time to first subsequent therapy or death (TFST), time to second progression (PFS2), time to second subsequent therapy or death (TSST), overall survival (OS)

 Safety, health-related quality of life (HRQoL*)

*Primary endpoint for HRQoL was trial outcome index (TOI) of the FACT-O (Functional Assessment of Cancer Therapy – Ovarian)

Presented by Pujade-Lauraine E, at SGO 2017 Annual Meeting. ASSESSMENT PFS BY INVESTIGATOR permission from from Elsevier. permission cancer and a BRCA1/2 mutation (SOLO2/ENGOT Reprinted The from Lancet 18(9), Oncol, Pujade

Median follow Progression-free survival (%) - up up was 22.1 months the in - Lauraine Lauraine E, - Ov21): Ov21): a double et al . Olaparib . Olaparib tablets as maintenance therapy in patients with platinum - blind, blind, randomised, placebo Months since randomisation since Months olaparib - controlled, controlled, phase 3 1274 trial, Median PFS, Median group group and months 22.2for placebo Events (%) Events months – 84. Copyri 107 (54.6) 107 Olaparib Olaparib (n=196) (n=196) - 19.1 sensitive, relapsed relapsed sensitive, ovarian ght ght 2017, with 80 (80.8) 80 Placebo Placebo (n=99) 5.5 NOVA STUDY

Phase III trial of maintenance therapy with in recurrent platinum-sensitive high-grade serous ovarian cancer

 Relapsed high-grade serous Primary endpoint Niraparib 300 mg QD histology or known gBRCA N=234 BICR-assessed PFS in 3 predefined mut Non-gBRCA cohorts 2:1  ≥2 prior regimens of R mut  gBRCA platinum-based Placebo  Overall Non-gBRCA chemotherapy N=116  Non-gBRCA HRD+  Responded to last platinum N=553 regimen; remains in Niraparib 300 mg QD Key secondary endpoints N=138 response and enrolled within  PRO, chemotherapy-free interval; 8 weeks of completion of gBRCA mut R 2:1 time to first subsequent last platinum regimen treatment; PFS2; time to second Placebo subsequent treatment; OS; safety  No measurable lesion N=65 >2 cm Exploratory analysis

Patient stratification Non-gBRCA mut cohort: PFS stratified by HRD/BRCA status  Time to disease progression on penultimate platinum-based therapy  HRD positive, sBRCA mut  Bevacizumab with last or penultimate chemotherapy  HRD-positive BRCA wt  CR/PR during last platinum regimen  HRD-negative Mirza MR, et al. N Engl J Med 2016;375:2154–2164. NOVA TRIAL: MAINTENANCE NIRAPARIB IN PLATINUM-SENSITIVE HGOC 1º Endpoint: BICR assessed PFS

Niraparib Niraparib Placebo (n=65) Placebo (n=116) (n=138) (n=234) Median PFS, months 21.0 5.5 Median PFS, months 9.3 3.9 HR=0.27 HR=0.45 95% CI 0.17, 0.41 95% CI 0.34, 0.61 P<0.001 P<0.001

From N Engl J Med, Mirza MR, et al, Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer, 375, 2154–64. Copyright © 2016, Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. NOVA EXPLORATORY ANALYSIS

PFS in non-gBRCA mut subgroups HRD positive HRD negative sBRCA mut (n=47) BRCA wt (n=115) (n=134)

Niraparib (n=35) Placebo (n=12) Niraparib (n=71) Placebo (n=44) Niraparib (n=92) Placebo (n=42) PFS median (95% CI) (Months) 20.9 (9.7–NR) 11.0 (2.0–NR) PFS median (95% CI) (Months) 9.3 (5.8–15.4) 3.7 (3.3–5.6) PFS median (95% CI) (Months) 6.9 (5.6–9.6) 3.8 (3.7–5.6)

Hazard ratio (95% CI); P value 0.27 (0.081–0.903); P=0.0248 Hazard ratio (95% CI); P value 0.38 (0.231–0.628); P=0.0001 Hazard ratio (95% CI); P value 0.58 (0.361–0.922); P=0.0226

% of patients without progression % of patients without progression % of patients without progression 62% 19% 45% 11% 27% 7% or death at 12 mo or death at 12 mo or death at 12 mo

% of patients without progression % of patients without progression % of patients without progression 52% 19% 27% 6% 19% 7% or death at 18 mo or death at 18 mo or death at 18 mo

100 100 100 Hazard ratio 0.27 (95% CI 0.08–0.90) Hazard ratio 0.38 (95% CI 0.23–0.63) Hazard ratio 0.58 (95% CI 0.36–0.92) P=0.02 P<0.001 P=0.02 75 75 75 Niraparib

50 50 50

free survival (%) survival free

free survival (%) survival free

free survival (%) survival free

-

- -

Niraparib 25 Placebo 25 25 Niraparib

Placebo

Progression Progression

Progression Placebo 0 0 0 0 2 4 6 8 10 12 14 16 18 20 22 24 0 2 4 6 8 10 12 14 16 18 20 22 24 0 2 4 6 8 10 12 14 16 18 20 22 24 No. at Risk No. at Risk No. at Risk Months since randomisation Months since randomisation Months since randomisation Niraparib 35 32 29 26 23 21 19 17 9 8 7 2 1 Niraparib 71 58 46 38 29 25 21 12 7 6 4 2 1 Niraparib 92 73 54 35 26 22 11 8 3 3 3 2 1 Placebo 12 9 7 4 4 3 1 1 1 1 1 1 1 Placebo 44 32 19 12 7 6 3 2 0 Placebo 42 35 19 11 7 6 2 2 0 From N Engl J Med, Mirza MR, et al., Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer, 375, 2154–64. Copyright © 2016, Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society; Mirza MR, et al. Ann Oncol. 2016;27(Suppl 6): Abstract LBA3_PR. ARIEL-3

Phase 3, randomised, double-blind study of vs. placebo following response to platinum-based chemotherapy for recurrent ovarian carcinoma study design

Patient eligibility Stratification

 High-grade serous or endometrioid  HRR gene mutation status by epithelial OC, primary peritoneal, or NGS analysis: fallopian tube cancers  BRCA1 or BRCA2  Sensitive to penultimate platinum † Rucaparib 600 mg BID  Non-BRCA HRR gene n=375  Responding to most recent platinum  None of the above (CR or PR)*  Response to recent platinum  Excludes patients without R 2:1 assessable disease following  CR

second surgery  PR Placebo BID  CA-125 within normal range  Progression-free interval after n=189  No restriction on size of residual penultimate platinum

tumour  6 to ≤12 months

 ECOG PS ≤1  >12 months

 No prior PARP inhibitors

*CR (defined by RECIST) or PR (defined by RECIST and/or a GCIG CA-125 response [CA-125 within normal range]) maintained until entry to ARIEL3 (≤8 weeks of last dose of chemotherapy). †ATM, ATR, ATRX, BARD1, BLM, BRIP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, MRE11A, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD52, RAD54L, RPA1.,BID. ARIEL3

Investigator-Assessed Progression-Free Survival

BRCA mutant Median HRD Median ITT Median (months) 95% CI (months) 95% CI (months) 95% CI Rucaparib 16.6 13.4–22.9 Rucaparib 13.6 10.9–16.2 Rucaparib 10.8 8.3–11.4 (n=130) (n=236) (n=375) Placebo 5.4 3.4–6.7 Placebo 5.4 5.1–5.6 Placebo 5.4 5.3–5.5 (n=66) (n=118) (n=189) HR, 0.23; HR, 0.32; HR, 0.36; 95% CI, 0.16–0.34; 95% CI, 0.30–0.45; P<0.0001 95% CI, 0.24–0.42; P<0.0001 P<0.0001

At risk (events) At risk (events) At risk (events) Rucaparib 130 (0) 93 (23) 63 (46) 35 (58) 15 (64) 3 (67) 0 (67) Rucaparib 236 (0) 161 (55) 96 (104) 54 (122) 21 (129) 5 (134) 0 (134) Rucaparib 375 (0) 228 128 65 (217) 26 (226) 5 (234) 0 (234) Placebo 66 (0) 24 (37) 6 (53) 3 (55) 1 (56) 0 (56) Placebo 118 (0) 40 (68) 11 (95) 6 (98) 1 (101) 0 (101) (111) (186) Rucaparib, 48% censored Placebo, 15% censored Rucaparib, 43% censored Placebo, 14% censored Placebo 189 (0) 63 (114) 13 (160) 7 (164) 2 (167) 1 (167) 0 (167) Rucaparib, 38% censored Placebo, 12% censored

Reprinted from The Lancet, Vol.390, Nº10106, Coleman RL, et al., The Lancet,, Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial, p1949-1961. Copyright 2017, with permission from Elsevier. WHEN PLATINUM IS AN OPTION

 Platinum-based combination

 Platinum-based combination PARP inhibitors

 Carboplatin + gemcitabine + bevacizumab  bevacizumab maintenance (for bevacizumab naïve)

 Platinum-based combination + bevacizumab  bevacizumab maintenance (for bevacizumab pre-treated in first line) WHEN PLATINUM IS AN OPTION

Bevacizumab in platinum-sensitive relapsed OC: the OCEANS trial

CBDCA AUC 4 GEM 1000 mg/m2 d1, 8

Placebo CG + placebo  Platinum-sensitive recurrent q3w until progression OC

 Measurable disease n=484  ECOG 0/1 CBDCA AUC 4

 No prior chemo for recurrent GEM 1000 mg/m2 d1, 8 OC

 No prior bevacizumab CG + Bevacizumab 15 mg/kg bevacizumab q3w until progression

Stratification variables: CG for 6 (up to 10) cycles

 Platinum-free interval (6-12 vs. >12 months)

 Cytoreductive surgery for recurrent disease (yes vs. no)

Epithelial ovarian, primary peritoneal, or fallopian tube cancer. Aghajanian C, et al. J Clin Oncol 30(17), 2012:2039–45 WHEN PLATINUM IS AN OPTION

OCEANS trial: PFS and OS results

Primary analysis of PFS1 Final OS2

1. Aghajanian C, et al. J Clin Oncol, 30(17), 2012:2039–45. Reprinted with permission. © 2012 American Society of Clinical Oncology; 2. Reprinted from Gynecol Oncol 139(1), Aghajanian C, et al. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer, 10–6. Copyright 2015, with permission from Elsevier. WHEN PLATINUM IS AN OPTION

 Platinum-based combination

 Platinum-based combination  PARP inhibitors

 Carboplatin + gemcitabine + bevacizumab  bevacizumab maintenance (for bevacizumab naïve)

 Platinum-based combination + bevacizumab  bevacizumab maintenance (for bevacizumab pre-treated in first line) WHEN PLATINUM IS AN OPTION

Bevacizumab beyond progression in platinum-sensitive bevacizumab pre-treated relapsed OC: the MITO-16/MaNGO OV-2 trial design

Carboplatin CG + placebo PLD or gemcitabine or paclitaxel Stage IIIB-IV EOC, FT or PPC progressing or recurring at least 6 months after front-line 1:1

Carboplatin 8 cycles chemotherapy plus avastin - (n≈400) PLD or gemcitabine or paclitaxel x6 CG + Avastin 15 mg/kg bevacizumab q3w

Primary endpoint

 PFS Until PD WHEN PLATINUM IS AN OPTION

MITO-16B/MaNGO OV-2B trial: PFS results

PFS Investigator assessed (Primary endpoint)

Standard Experimental Log Rank P No. of events 161 143 Median PFS 8.8 months 11.8 months <0.001 HR* (95% CI) 0.51 (0.41-0.65) *Adjusted by: Age, PS, centre size, bevacizumab at relapse, chemo backbone, residual disease at initial surgery

Pignata S, et al. J Clin Oncol 36, 2018 (suppl; abstr 5506). Presented at ASCO Annual Meeting 2018. WHEN PLATINUM IS AN OPTION

Treatment algorithm BRCA mutated or WT

Platinum based treatment Platinum based treatment SECOND LINE

Radiologic Carbo-gem CR or PR + bevacizumab

Olaparib/ niraparib Bevacizumab MAINTENANCE

Platinum based ct Platinum based treatment THIRD LINE

If TFIp 6-12 months consider

Pld + trabectedin Olaparib/ niraparib

TFIp 6-12 months FOURTH LINE

Pld + trabectedin

Platinum based ct CONCLUSIONS

 Platinum free interval is not the only parameter to be considered to select treatment for recurrence. Other parameters including biology, pathology and previous target maintenance therapy need to be taken into account.

 Recurrent OC patients are classified for being candidate or not to a platinum re-treatment.

 Indication for surgery must be assessed although final results of trials are still pending.

 Platinum combination chemotherapy is more effective than single agent platinum.

 In patients who respond to a platinum based therapy, PARP-i maintenance is effective in prolonging PFS, with higher effect in BRCA mutated patients.

 Platinum based therapy plus bevacizumab prolongs PFS compared to chemo alone, both in patients who are bevacizumab naive or bevacizumab pre-treated. Bev-containing regimens given in preference to patients at high risk of quick progression and large bulk of disease.

 In patients with TFI between 6–12 months, not candidate for platinum, trabectedine-PLD should be considered. THANK YOU!