Clinical Situation: Platinum-Sensitive Recurrence

Platinum-Sensitive (Pt-S): Treatment given for recurrence occurring 6 months or more after last platinum-based treatment

Platinum-Sensitive (Pt-S): Treatment given for recurrence occurring 6 months or more after last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Drug Class Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Standard of Care Chemotherapy
Chemotherapy NCT00002894 III Cisplatin, Carboplatin, Paclitaxel A Randomized Trial of Paclitaxel (Taxol) in Combination With Platinum Chemotherapy vs. Conventional Platinum-Based Chemotherapy in the Treatment of Women With Relapsed Ovarian Cancer (ICON4)

Improved PFS and OS with addition of paclitaxel to platinum

CisPt/CarboPt+Pac vs CisPt/CarboPt:

ORR: 66 vs 54%
PFS: 12 vs 9 months*
OS: 29 vs 24 months*

v. 6/2017

Chemotherapy NCT00102414 III Carboplatin, Gemcitabine A Randomized Phase III Study Comparing Gemcitabine Plus Carboplatin Versus Carboplatin Monotherapy in Patients With Advanced Epithelial Ovarian Carcinoma Who Failed First-Line Platinum-Based Therapy (NCIC OV15)

Improved PFS with addition of gemcitabine to carboplatin

CarboPt+Gem vs. CarboPt:

ORR: 47.2 vs 30.9%*
PFS: 8.6 vs. 5.8 months*

v. 6/2017

Chemotherapy NCT00538603 III Carboplatin, Liposomal doxorubicin, Paclitaxel Multi-national, Randomized, Phase III, GCIG Intergroup Study Comparing Pegylated Liposomal Doxorubicin (CAELYX) and Carboplatin vs. Paclitaxel and Carboplatin in Patients With Epithelial Ovarian Cancer in Late Relapse. (CALYPSO)

Carboplatin+liposomal doxorubicin has similar PFS and OS to carboplatin+paclitaxel with less sensory neuropathy

CarboPt+PLD vs CarboPt+Pac:

PFS: 11.3 vs 9.4 months*
OS: 30.7 vs 33.0 months

v. 6/2017

Standard of Care Targeted Drugs
DNA Damage Repair Pathway Inhibitors:PARP NCT01078662 II Olaparib A Phase II, Open Label, Non Randomised, Non Comparative, Multicentre Study to Assess the Efficacy and Safety of Olaparib Given Orally Twice Daily in Patients With Advanced Cancers Who Have a Confirmed Genetic BRCA 1 and/or BRCA2 Mutation (Study 42)

Olaparib shows promising responses in heavily pretreated gBRCA MUT patients

ORR: 46%
PFS: 9.4 months

v. 9/2018

DNA Damage Repair Pathway Inhibitors:PARP Rucaparib FDA Approval Data II Rucaparib Treatment of BRCA-mutated Ovarian Cancer After 2 or More Chemotherapies

Rucaparib shows promising responses in BRCA MUT patients

ORR: 66%

v. 9/2018

Angiogenesis Inhibitors: VEGF NCT00434642 III Bevacizumab, Carboplatin, Gemcitabine A Phase III, Multicenter, Randomized, Blinded, Placebo-controlled Trial of Carboplatin and Gemcitabine Plus Bevacizumab in Patients With Platinum-sensitive Recurrent Ovary, Primary Peritoneal, or Fallopian Tube Carcinoma (OCEANS)

Improved ORR and PFS with addition of bevacizumab to carboplatin and gemcitabine, but no OS difference

CarboPt+Gem+Bev vs CarboPt+Gem+Placebo:

ORR: 78.5 vs 57.4%*
PFS: 12.4 vs 8.4 months*
OS: 33.6 vs 32.9 months

v. 1/2017

Angiogenesis Inhibitors: VEGF NCT00565851 III Bevacizumab, Carboplatin, Paclitaxel A Phase III Randomized Controlled Clinical Trial of Carboplatin and Paclitaxel (or Gemcitabine) Alone or in Combination With Bevacizumab (NSC #704865) Followed by Bevacizumab and Secondary Cytoreductive Surgery in Platinum-Sensitive, Recurrent Ovarian, Peritoneal Primary and Fallopian Tube Cancer. NCI-Supplied Agents: Bevacizumab (NSC #704865) (GOG 0213)

Improved ORR, PFS and OS with the addition of bevacizumab to carboplatin + paclitaxel

CarboPt+Pac+Bev vs CarboPt+Pac:

ORR: 78 vs 59%*
PFS: 13.8 vs 10.4 months*
OS: 42.2 vs 37.3 months*

v. 7/2018

Angiogenesis Inhibitors: VEGF NCT01837251 III Bevacizumab, Carboplatin, Gemcitabine, Liposomal doxorubicin A Prospective Randomized Phase III Trial of Carboplatin/Gemcitabine/Bevacizumab vs. Carboplatin/Pegylated Liposomal Doxorubicin/Bevacizumab in Patients With Platinum-sensitive Recurrent Ovarian Cancer

Improved PFS with addition of liposomal doxorubicin to carboplatin+bevacizumab compared to gemcitabine

CarboPt+Gem+Bev vs CarboPt+PLD+Bev:

PFS: 11.7 vs 13.3 months*

v. 11/2018

Drugs in NCCN Guidelines
Angiogenesis Inhibitors: VEGF NCT01305213 II Bevacizumab, Fosbretabulin A Randomized Phase II Evaluation of Single-Agent Bevacizumab (NSC #704865) and Combination Bevacizumab With Fosbretabulin Tromethamine (CA4P) (NSC #752293) in the Treatment of Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma

Improved PFS with addition of fosbretabulin to bevacizumab

Fos+Bev vs Bev:

PFS: 7.6 vs 6.1 months

v. 4/2017

Drugs in Clinical Development
DNA Damage Repair Pathway Inhibitors:PARP NCT01116648 II Cediranib, Olaparib Phase I/II Study of Cediranib and Olaparib in Combination for Treatment of Recurrent Papillary-Serous Ovarian, Fallopian Tube, or Peritoneal Cancer or for Treatment of Recurrent Triple-Negative Breast Cancer

Improved ORR and PFS for olaparib+cediranib combination, particularly in patients with gBRCA WT or unknown BRCA status

Ola+Ced vs Ola:

gBRCA WT or UNK:
ORR: 76 vs 32%*
PFS: 23.7 vs 5.7 months*
gBRCA MUT:
ORR: 83 vs 63%
PFS: 16.4 vs 16.5 months

v. 6/2017

DNA Damage Repair Pathway Inhibitors:PARP NCT01540565 II Veliparib A Phase II Evaluation of the Poly (ADP-Ribose) Polymerase (PARP)-1 and -2 Inhibitor Veliparib (ABT-888) (NSC#737664) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Who Carry a Germline BRCA1 or BRCA2 Mutation

Veliparib shows encouraging activity in gBRCA MUT cancer

ORR: 35%
PFS: 11.0 months

v. 1/2017

DNA Damage Repair Pathway Inhibitors:PARP NCT01891344 II Rucaparib A Phase 2, Open-Label Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2 Part1)

Improved ORR and PFS with rucaparib treatment in BRCA MUT patients

BRCA MUT vs BRCA WT LOH high vs BRCA WT LOH low:

ORR: 80 vs 29 vs 10%*
PFS: 12.8 vs 5.7 vs 5.2 months*

v. 4/2017

DNA Damage Repair Pathway Inhibitors:PARP NCT02354586 II Niraparib A Phase 2, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Niraparib in Patients With Advanced, Relapsed, High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Have Received Three or Four Previous Chemotherapy Regimens (QUADRA)

Niraparib shows promising activity in late-line treatment setting

BRCA MUT:
ORR: 39%
HRD-positive (incl. BRCA MUT):
ORR: 27%

v. 11/2018

DNA Damage Repair Pathway Inhibitors:PARP NCT02734004 I/II Durvalumab, Olaparib A Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) in Combination With Olaparib (PARP Inhibitor) in Patients With Advanced Solid Tumors (MEDIOLA)

Promising activity of olaparib+durvalumab combination in gBRCA MUT

ORR: 72%
DCR (3 months): 81%

v. 8/2018

Cell Cycle Inhibitors:p53 NCT02098343 II APR-246, Carboplatin, Liposomal doxorubicin PiSARRO: p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246

Encouraging activity of APR-246+carboplatin+liposomal doxorubicin in TP53-mutated platinum-sensitive and partially platinum-sensitive patients

ORR: 62%
PFS: 10.5 months

v. 8/2018

Immunotherapy: Checkpoint Inhibitors/CTLA-4 NCT01611558 II Ipilimumab A Phase II Safety and Efficacy Study of Ipilimumab Monotherapy in Recurrent Platinum Sensitive Ovarian Cancer Subjects

Ipilimumab shows encouraging anti-tumor activity, but with serious side effects

ORR: 10.3%

v. 4/2017

Immunotherapy: Antibodies/FRalpha NCT00849667 III Carboplatin, Farletuzumab, Paclitaxel A Randomized, Double-blind, Placebo-Controlled, Phase 3 Study to Assess the Efficacy and Safety of Weekly MORAb-003 in Combination With Carboplatin and Taxane in Subjects With Platinum-sensitive Ovarian Cancer in First Relapse

PFS and OS benefit with addition of farletuzumab to carboplatin+paclitaxel in patients with baseline CA125 levels ≤3xULN

CarboPt+Pac+Far vs CarboPt+Pac+Placebo:

PFS: 13.6 vs 8.8 months*
OS: Not Reached vs 29.1 months*

v. 11/2017

*Statistically significant result

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