Should Bevacizumab Be Continued After Progression on Bevacizumab in Recurrent Ovarian Cancer?

2013 ◽  
Vol 23 (5) ◽  
pp. 833-838 ◽  
Author(s):  
Floor J. Backes ◽  
Debra L. Richardson ◽  
Georgia A. McCann ◽  
Blair Smith ◽  
Ritu Salani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Bowel Perforation ◽  
Objective Response ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Response Rates ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Cytotoxic Chemotherapy

ObjectiveThe optimal role of bevacizumab (Bev) in the treatment of ovarian cancer has not yet been established. Furthermore, it is unclear whether there is a benefit of Bev after progression on a Bev-containing regimen in ovarian cancer. The objective of this study was to compare response rates, progression-free survival (PFS), and overall survival between patients who were treated with chemotherapy and Bev after progression on Bev (BAB) versus patients who were treated with chemotherapy without Bev (CWOB).MethodsWe conducted a retrospective chart review of all patients who received treatment with Bev (with or without cytotoxic chemotherapy) for recurrent ovarian cancer at a single institution. Patients who received additional therapy after progression while on Bev were included.ResultsForty-six patients were included (16 CWOB group and 30 BAB). The median number of previous chemotherapy regimens was 2.5 for CWOB compared with 4 for BAB (P= 0.11). Fifty-two percent of patients had an objective response to the first Bev regimen before progressing on Bev. Response rates for the regimen after progression on Bev were 19% (3/16) in the CWOB group and 23% (7/30) in the BAB group (P= 1). Twenty-five percent of the patients who responded to the first Bev regimen and 18% of those who did not respond to the first Bev regimen responded to the second Bev regimen (P= 0.72). The median PFS for patients in the CWOB group was 2.6 months (95% confidence interval [CI], 1.3–5 months), compared with 5.0 months (95% CI, 3.5–7.3 months) for patients in the BAB group (P= 0.01). Overall survival was similar, 9.4 months (95% CI, 5.0–12.0 months) for CWOB versus 8.6 months (95% CI, 5.8–15.5 months) for BAB (P= 0.19). One patient in the BAB group died of a bowel perforation.ConclusionsIn patients previously treated with Bev for recurrent ovarian cancer, the subsequent addition of Bev to cytotoxic chemotherapy increased the PFS compared with patients not receiving a second course of Bev, but did so without an impact on overall survival. The response to the first Bev regimen did not predict whether a patient would respond again to the next Bev regimen. Randomized, larger studies will have to be performed to confirm this observation.

Does repeat usage of bevacizumab in patients with progressive recurrent ovarian cancer offer a survival advantage?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16510-e16510
Author(s):  
D. L. Richardson ◽  
F. J. Backes ◽  
L. G. Seamon ◽  
L. G. Seamon ◽  
J. D. Hurt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Treatment Regimen ◽  
Bowel Perforation ◽  
Group Versus ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Cytotoxic Chemotherapy ◽  
Group 13 ◽  
Additional Therapy

e16510 Background: Many studies show bevacizumab (BEV) has activity in the treatment of recurrent ovarian cancer, especially when combined with cytotoxic chemotherapy. However, it is uncertain whether BEV should be continued if a patient progressives on treatment which includes BEV. Therefore, our objective is to compare response rates (RR), progression-free survival (PFS), and overall survival (OS) between patients who continued on BEV after progression on BEV (BPB) versus patients who were treated with cytotoxic chemotherapy without BEV (no BPB). Methods: All patients who received treatment with BEV (with or without cytotoxic chemotherapy) for recurrent ovarian cancer at a single institution were identified. Patients who received additional therapy after progression on BEV were included. Patients who were treated on GOG 218 or received first-line BEV or had their first BEV therapy discontinued due to side effects from BEV were excluded. RR were assessed using RECIST criteria, CA125 levels, or progressive disease symptoms. PFS was defined as the period from initiation of the treatment regimen until progression or date of last contact. OS was defined as the period from initiation of the second treatment regimen until death or date of last contact. Results: 35 patients met inclusion criteria. The median number of previous chemotherapy regimens was 4 (range 1–8). About 50% of the patients had a CR or PR prior to progressing on BEV. There were 27 patients in the BPB group, and 8 patients in the no BPB group. 13% (1/7) of patients responded to cytotoxic chemo after BEV, and 15% (4/27) of patients responded to repeat treatment with BEV, p = 1. The median PFS for patients in the no BPB group was 4.6 months (95% CI 1.6–5 mo), compared to 4.8 months (2.7–7.5 mo) for patients in the BPB group, p = 0.11. There was no difference in OS, 9.8 months (95% CI 2.73- ∞) versus 8.4 months (95% CI 5.8–15.6 months) p = 0.43 for patients in the no BPB group versus the BPB group. One patient in the BPB group died of a bowel perforation. Conclusions: We offer the first comparison of PFS and OS in patients treated with cytotoxic chemotherapy ± BEV after progression on BEV. After progressing on a BEV regimen, there was no difference in the PFS, OS or RR in those pts treated with or without BEV with an overall OS < 1 year. [Table: see text]

Nonplatinum Topotecan Combinations Versus Topotecan Alone for Recurrent Ovarian Cancer: Results of a Phase III Study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group

2008 ◽  
Vol 26 (19) ◽  
pp. 3176-3182 ◽  
Author(s):  
Jalid Sehouli ◽  
Dirk Stengel ◽  
Guelten Oskay-Oezcelik ◽  
Alain G. Zeimet ◽  
Harald Sommer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Refractory

PurposeThe management of recurrent ovarian cancer remains controversial. Single-agent topotecan is an established treatment option, and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine.Patients and MethodsWomen with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were randomly assigned to topotecan monotherapy 1.25 mg/m2/d, topotecan 1.0 mg/m2plus oral etoposide 50 mg/d, or topotecan 0.5 mg/m2/d plus gemcitabine 800 mg/m2on day 1 and 600 mg/m2on day 8 every 3 weeks. Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months, respectively. The primary end point was overall survival. Secondary end points included progression-free survival, objective response rates, toxicity, and quality of life (as measured by the European Organisation for Research and Treatment of Cancer [EORTC] 30-item Quality-of-Life Questionnaire).ResultsThe trial enrolled 502 patients with a mean age of 60.5 years (± 10.2 years), 208 of whom were platinum resistant. Median overall survival was 17.2 months (95% CI, 13.5 to 21.9 months) with topotecan, 17.8 months (95% CI, 13.7 to 20.0 months) with topotecan plus etoposide (log-rank P = .7647), and 15.2 months (95% CI, 11.3 to 20.9 months) with topotecan plus gemcitabine (log-rank P = .2344). Platinum-sensitive patients lived significantly longer than platinum-refractory patients (21.9 v 10.6 months). The median progression-free survival was 7.0, 7.8, and 6.3 months, respectively. Objective response rates were 27.8%, 36.1%, and 31.6%, respectively. Patients under combined treatment were at higher risk of severe thrombocytopenia.ConclusionNonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer.

scholarly journals Real-World Experience of Olaparib Maintenance in High-Grade Serous Recurrent Ovarian Cancer Patients with BRCA1/2 Mutation: A Korean Multicenter Study

2019 ◽  
Vol 8 (11) ◽  
pp. 1920 ◽  
Author(s):  
Paik ◽  
Lee ◽  
Lee ◽  
Shin ◽  
Park ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Real World ◽  
Partial Remission ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
High Grade ◽  
Platinum Sensitive

Background: Olaparib maintenance therapy has shown efficacy and tolerability in patients with platinum-sensitive, high-grade serous recurrent ovarian cancer (HSROC) with BRCA1/2 mutation (BRCAm). Our aim was to present real-world experience with olaparib in Korea. Method: We included HSROC patients with BRCAm treated with olaparib maintenance at four institutions in Korea between 2016 and 2018. Medical records were reviewed for clinico-pathologic characteristics, objective response, survival outcomes, and safety. Results: One hundred HSROC patients with BRCAm were included. BRCA1 mutation was present in 71 patients (71.0%), and BRCA2 mutation was present in 23 patients (23.0%). In terms of the best objective response with olaparib maintenance in 53 patients with partial remission from most recent chemotherapy, complete remission occurred in 12 (22.6%) and partial remission in four (7.5%), while 33 patients (62.3%) had stable disease. The 24 month progression-free survival was 42.4%, and 24 month overall survival was 82.1%. Grade 3 or more adverse events were as follows: anemia in 14 patients (14.0%), neutropenia in seven patients (7.0%), thrombocytopenia in two patients (2.0%), oral mucositis in one patient (1.0%), and soft tissue infection in one patient (1.0%). Conclusions: The safety and effectiveness of olaparib maintenance treatment in a real-world study were consistent with those reported in previous clinical trials.

Cyclophosphamide, Adriamycin, Vincristine and Prednisone Plus Rituximab (CHOP-R) in Fludarabine (F) Refractory Chronic Lymphocytic Leukemia (CLL) or CLL with Autoimmune Cytopenia (AIC) or Richter's Transformation (RT): Final Analysis of a Phase II Study of the German CLL Study Group

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2860-2860
Author(s):  
Petra Jenke ◽  
Barbara Eichhorst ◽  
Raymonde Busch ◽  
Nadine Anheier ◽  
Ulrich Duehrsen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Research Funding ◽  
Progression Free Survival ◽  
Response Rates ◽  
Median Number ◽  
Response Evaluation ◽  
Free Survival ◽  
Richter's Transformation ◽  
Grade 3

Abstract Abstract 2860 Introduction: In the last decade, important progress has been achieved in the treatment of CLL through the use of purine analog-based chemoimmunotherapies. Several conditions remain a challenge, often with a poor outcome. Amongst these therapeutic problems are Richter's transformation (RT), refractoriness to F-based therapies (Fref), and the occurrence of AIC, which are sometimes induced by F. Fref and RT pts have a very poor prognosis with an estimated overall survival (OS) of only 10 and 8 months (mos), respectively. Therefore, therapeutic alternatives are urgently warranted. CHOP-R has improved the outcome of pts with aggressive non-Hodgkin's lymphoma. To test the efficacy and tolerability of the CHOP-R regimen in CLL patients with RT, Fref, or AIC, the GCLLSG initiated a prospective phase II trial. Material and Methods: 62 patients were included in the study. Due to protocol violations, 2 patients were excluded. Within the group of Fref pts, the medical review detected 11 patients who had received pre-treatment with F (Fpret), but were not refractory according to the updated guidelines (Hallek et al., Blood 2008). Thus, 26 pts were classified as Fref/pret, 19 pts as AIC and 15 pts as RT. All patients received CHOP every 3 weeks (cyclophosphamide 750mg/m2, adriamycin 50mg/m2 and vincristine 1, 4mg/m2 d1; prednisone 100mg/m2 d1–5). Rituximab was added starting with the 2nd cycle (375mg/m2 on each d0, and 21 days after the last CHOP-R). RT pts received up to 8, Fref/pret and AIC up to 6 courses of CHOP-R. In case of PD after 3 cycles, pts went off-study. The primary endpoints were remission rate, quality and duration of response. Results: 79%, 73%, and 40% of AIC, Fref/pret, and RT pts were male, respectively. The median age was 65 years (y) for Fref/pret-pts, 66y in the AIC and 69y in the RT group. Binet stages for Fref/pret pts were: A: 8%; B: 27% C: 65 %. All but 3 AIC pts were at Binet stage C. Initial RT stages according to Ann Arbor were: II: 13%, III: 13%, IV 73%. The median number of previous therapies were 3 for Fref/pret, 2 for AIC and 2 for RT. A total of 314 cycles were administered, with a median number of 3 cycles for AIC and Fref pts and a median number of 4 cycles for the RT group. Due to toxicity 73% of cycles in the Fref/pret group, 66% in the AIC and 87% in the RT group were dose-reduced. 69% of Fref/pret-pts and 58% of AIC-pts received full 6 cycles of therapy and only 40% of RT-pts completed 8 cycles of therapy. Treatment was stopped in 6 pts because of PD. Due to treatment related toxicity treatment was stopped in 16 pts (27%). Treatment related mortality was 3% (2 pts). Treatment toxicity was reported according to NCI common toxicity criteria (CTC) version 2.0. Adverse events grade 3 or 4 for anemia, neutropenia and thrombocytopenia were documented in 75%, 55% and 65% of patients, respectively. Infections were the most common non-hematologic toxicity and occurred in 67%; severe infections CTC grade 3 or 4 occurred in 28%. All 26 Fref/pret-pts were available for response evaluation. CHOP-R achieved 54% PR, 35% SD and 12% PD. The median progression-free survival (PFS) and median treatment-free survival (TFS) were 11 and 14 mos. OS was 27 mos with a significant difference concerning F-ref (n=15) and F-pret (n=11) pts (17 vs. 35m; p=0.05). We evaluated the response of all 15 RT-pts with 60% PR, 7% CR, 13% SD and 20% PD. The PFS was 15 mos, TFS was 17 mos and OS 27 mos. 17 AIC pts were available for response evaluation with 82% PR, 6% SD and 12% PD. The PFS and TFS were only 14 and 16 mos. The OS was 50 mos. The population had a high incidence of unfavourable genetic markers: deletion of chromosome 17p [del(17p)] was detected in 24%, del(11q) in 34% and unmutated IGHV in 70%. 85% had high levels of serum thymidine kinase (sTK > 10 U/l), and 49% had high levels of ß2-microglobulin (ß2M > 3.5 mg/l). Patients with del(17p) had an unfavourable response rate and achieved significant less a PR or CR (36% vs. 76%; p=0.03). Multivariate analyses showed that del(17p) and ECOG performance status had a negative prognostic impact on OS (p<0.0001). Moreover the presence of a del(17p) predicted a short PFS (6 vs. 16.9 mos; p=0.001). Conclusion: CHOP-R achieves promising response rates in CLL patients with Fref and RT and very good response rates in patients with AIC. However, the progression-free survival and overall survival remain unsatisfactory. Therefore, CHOP-R might be used as induction therapy prior to allogeneic stem cell transplantation in physically fit patients. Disclosures: Eichhorst: Hoffmann La Roche: Honoraria, Research Funding, Travel Grants; Mundipharma: Research Funding, Travel Grants; Gilead: Consultancy. Dreyling:Roche: Research Funding, Scientific advisory board, Speakers Bureau. Bergmann:Celgene: Honoraria. Stilgenbauer:Hoffmann La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Travel Grants. Fink:Hoffmann La Roche: travel grants. Fischer:Hoffmann La Roche:. Wendtner:Hofmann-La Roche: Consultancy, Honoraria, Research Funding. Hallek:Roche: Consultancy, Honoraria, Research Funding; Mundipharma: Research Funding; Celgene: Honoraria.

European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion.

1994 ◽  
Vol 12 (12) ◽  
pp. 2654-2666 ◽  
Author(s):  
E A Eisenhauer ◽  
W W ten Bokkel Huinink ◽  
K D Swenerton ◽  
L Gianni ◽  
J Myles ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Rates ◽  
Dose Effect ◽  
Response Analysis ◽  
High Dose ◽  
End Points ◽  
Short Infusion

PURPOSE Taxol (paclitaxel; Bristol-Myers Squibb, Wallingford, CT) is a new anticancer agent with activity in a number of human tumors, including epithelial ovarian cancer. In nonrandomized trials, doses studied have ranged from 135 mg/m2 to 250 mg/m2 administered over 24 hours with premedication to avoid hypersensitivity reactions (HSRs). This study addressed two questions: the dose-response relationship of Taxol in relapsed ovarian cancer and the safety of a short infusion given with premedication. METHODS Women with platinum-pretreated epithelial ovarian cancer and measurable recurrent disease were randomized in a bifactorial design to receive either 175 or 135 mg/m2 of Taxol over either 24 or 3 hours. Major end points were the frequency of significant HSRs and objective response rate. Secondary end points were progression-free and overall survival. RESULTS Of 407 patients randomized, 391 were eligible and 382 assessable for response. Analysis was performed according to the bifactorial design. Severe HSRs were rare (1.5% patients) and were not affected by either dose or schedule. Response was slightly higher at the 175-mg/m2 dose (20%) than at 135 mg/m2 (15%), but this was not statistically significant (P = .2). However, progression-free survival was significantly longer in the high-dose group (19 v 14 weeks; P = .02). Significantly more neutropenia was seen when Taxol was administered as a 24-hour infusion. Response rates were similar in the 24- and 3-hour groups (19% and 16%, respectively; P = .6). No survival differences were noted. CONCLUSION The 3-hour infusion of Taxol is safe when given with premedication and is associated with less neutropenia. There is a modest dose effect with longer time to progression at 175 mg/m2. The observation that longer infusion produces more myelosuppression but does not yield higher response rates should lead to further studies to determine the optimal dose and schedule of this interesting new agent.

A phase II trial of combination irinotecan and oral etoposide chemotherapy in recurrent ovarian cancer: A Tohoku Gynecologic Cancer Unit (TGCU) study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5558-5558
Author(s):  
S. Kumagai ◽  
T. Shoji ◽  
Y. Yokoyama ◽  
T. Takano ◽  
H. Mizunuma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Treatment Options ◽  
Gynecologic Cancer ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Oral Etoposide ◽  
Eligibility Criteria ◽  
Platinum Resistant

5558 Background: Various problems still exist in the management of recurrent ovarian cancer and there are limited treatment options especially for the platinum resistant patients (pts). We conducted a phase II study to evaluate the efficacy and safety of the combination irinotecan/oral etoposide chemotherapy. Methods: Eligibility criteria included recurrent ovarian cancer with measurable disease or positive CA125, preserved organ function, and aged 20–75. Treatment was conducted with irinotecan (60 mg/m2 iv, day 1, 15) and oral etoposide (50 mg/body day 1–21), q 28 days until disease progression or unacceptable toxicity. Primary endpoint was response rate (RR) and secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). Results: 38pts were enrolled on this study from May 2003 to April 2007, and all pts were eligible. Median age was 57 yrs (range 37–74). PS 0 in 24 pts, 1 in 10 pts, and 2 in 4 pts. Median number of previous regimen was 2 (range 1–4). Median treatment cycles were 6 (range 2–27). RR (CR+PR) was 18/38 (47.4%), and CR+PR+SD rate was 31/38 (81.6%). Grade 3/4 adverse effect included leukopenia (50.0%), neutropenia (52.6%), anemia (18.4%) and thrombocytopenia (2.6%), nausea/vomiting (7.9%) and diarrhea (2.6%). Treatment-related death was not observed. Median PFS was 7 months (range 1–33) and OS was 19 months (range 4–60). Among 20 pts with platinum resistant cases, RR was 6/20 (30.0%), CR+PR+SD rate was 14/20 (70.0%), median PFS was 6 months (range 1–33), and OS was 24 months (range 5–60). Conclusions: Combination irinotecan/oral etoposide chemotherapy can achieve a superior management for the recurrent ovarian cancer without declining QOL, and also has the possibility to be one of the most effective regimens as second-line chemotherapy. No significant financial relationships to disclose.

A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA5500-LBA5500 ◽  
Author(s):  
Joyce Liu ◽  
William Thomas Barry ◽  
Michael J. Birrer ◽  
Jung-min Lee ◽  
Ronald J. Buckanovich ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase 1 ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Parp Inhibitors ◽  
Open Label ◽  
Angiogenic Therapy ◽  
Platinum Sensitive

LBA5500 Background: PARP inhibitors and anti-angiogenics are clinically active in recurrent ovarian cancer (OvCa). Preclinical studies suggest these agents can synergize, and a phase 1 study showed that the combination of cediranib (ced) and olaparib (olap) is well-tolerated. We therefore compared the activity of olap alone (Olap) to combined ced and olap (Ced/Olap) in treatment of recurrent platinum-sensitive (plat-sens) high-grade serous (HGS) or BRCA-related OvCa (NCT 01116648). Methods: Patients (pts) across 9 centers were randomized 1:1 in this Ph 2 open label study to Olap (olap 400 mg capsules BID) or Ced/Olap (olap 200 mg capsules BID; ced 30 mg daily), stratified by BRCA status and prior anti-angiogenic therapy. Eligibility included pts with recurrent plat-sens HGS or BRCA-related OvCa. Pts had measurable disease by RECIST 1.1, PS 0 or 1, and the ability to take POs. No prior anti-angiogenics in the recurrent setting or prior PARP inhibitor was allowed. Progression-free survival (PFS) was defined as time from randomization to radiographic progression or death. With a target N=90 pts, the study was powered to detect a hazard ratio (HR) of 1.75 (median PFS 6 vs 10.5 mo). Results: Pts were enrolled from Oct 2011 to Jun 2013: 46 to Olap, 44 to Ced/Olap. 48 pts were known BRCA carriers (25 Olap; 23 Ced/Olap). At a planned interim analysis the DSMB recommended release of data. As of Jan 7, 2014, 41 pts had a PFS event. Median PFS was 9.0 mos for Olap and 17.7 mos for Ced/Olap (HR 2.9, 95% CI 1.5-5.6, p = 0.001). There were 2 complete responses (CR) and 21 partial responses (PR) in pts on Olap (56% objective response rate, ORR) and 3 CRs and 33 PRs in pts on Ced/Olap (84% ORR, p = 0.008). The overall rate of Gr3/4 toxicity was higher for pts on Ced/Olap (70%) than on Olap (7%). Differentially occurring toxicities included fatigue (27% Ced/Olap vs 7% Olap), diarrhea (23% vs 0%), and hypertension (39% vs 0%). Updated efficacy and exploratory subgroup analyses will be presented. Conclusions: Combined Ced/Olap significantly extended PFS and ORR compared to Olap in plat-sens OvCa. Further studies of this oral combination in plat-sens OvCa are warranted. Clinical trial information: NCT01116648.

Overall survival results of ICON6: A trial of chemotherapy and cediranib in relapsed ovarian cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5506-5506 ◽  
Author(s):  
Jonathan A. Ledermann ◽  
Andrew C. Embleton ◽  
Timothy Perren ◽  
Gordon C. Jayson ◽  
Gordon J. S. Rustin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Sample Size ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Primary Analysis ◽  
Logrank Test ◽  
Double Blind ◽  
Time To Death ◽  
Platinum Sensitive

5506 Background: ICON6 is a three-arm double-blind, placebo-controlled phase 3 trial of cediranib in platinum-sensitive relapsed ovarian cancer (NCT00532194). The primary analysis (Ledermann et al Lancet 2016) showed a significant (p < 0.0001), 2.3 month extension in progression-free survival (PFS) using cediranib with chemotherapy and as maintenance compared to chemotherapy and placebo. We present the final overall survival (OS) results. Methods: The trial was originally designed to recruit 2000 patients with OS as the primary endpoint. AstraZeneca discontinued cediranib development in Sep 2011, leading to an unplanned redesign prior to analysis. The sample size was reduced and primary outcome became PFS, comparing two arms, placebo (A) to cediranib given with chemotherapy and as maintenance (C). In arm B cediranib was given with chemotherapy followed by placebo maintenance. Analysis of PFS was performed on a sample size of 456 patients receiving a 20mg dose of cediranib. At the primary analysis, 52% patients had died; this mature OS analysis was performed after 85% patients died. Results: The OS analysis was performed at a median 25.6 months follow up; 102/118 (86%) died in A and 140/164 (85%) in C. In A the median survival was 19.9 months (95% CI: 17.4, 26.5) and in C 27.3 months (24.8, 33.0). Using the logrank test the Hazard Ratio estimate was 0.85 (0.66, 1.10) in favour of cediranib (p = 0.21). Evidence of non-proportionality of the survival curves was observed (p = 0.0029), so we measured the Restricted Mean Survival Time as an alternative to the median. Over 6 years, there was a 4.8 month (-0.1, 9.8) increase in time to death in C compared to A, from 29.4 to 34.2 months. The mean for arm B (32.0 months) was consistent with a benefit of increased use of cediranib. Conclusions: Cediranib has demonstrated a significant effect in increasing PFS. The mature survival analysis (85%) shows an improvement in median OS of 7.4 months, and an incremental benefit with increased cediranib use. The previously published significant PFS benefit coupled with the increase in OS highlights the potential value of cediranib in platinum-sensitive recurrent ovarian cancer. Further exploration of cediranib in this setting is underway. Clinical trial information: NCT00532194.

Apatinib as a salvage treatment in gynecologic cancer patients failed from two or more lines of prior chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17009-e17009 ◽  
Author(s):  
Congying Xie ◽  
Meng Su ◽  
Xiance Jin
Keyword(s):  
Ovarian Cancer ◽  
Cervical Cancer ◽  
Cancer Patients ◽  
Gynecologic Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Recurrent Ovarian Cancer ◽  
Kaplan Meier ◽  
Hand Foot Syndrome

e17009 Background: The aim of this study was to evaluate the efficacy and safety of apatinib, an oral VEGFR2 inhibitor, in the treatment of advanced cervical and ovarian cancer patients who failed from two or more lines of chemotherapy. Methods: The advanced cervical and ovarian cancer patients, who experienced two or more lines of chemotherapy and treated with apatinib from April 2015 to January 2017, were retrospectively reviewed. All eligible patients received continuous apatinib treatment until disease progression, death, or intolerable toxicity. Survival and toxicities outcome were evaluated by Kaplan-Meier method and according to NCI-CTC4.0. Results: Twenty-six patients were eligible (cervical cancer:12 and ovarian cancer:14). After dose adjustment, 14 patients (53.8%) received 500 mg daily of apatinib, 8 patients received 250mg, 3 received 425mg and 1 received 675mg daily. The median progression-free survival (PFS) of cervical cancer and ovarian cancer were 8 months (95%CI:3.83-12.17) and 4 months (95%CI:1.57-6.44), respectively. Objective response rates in cervical cancer and ovarian cancer were 50% and 50%, respectively. Disease control rates were 100% for cervical cancer and 71.4% for ovarian cancer. Complete response was not observed in either cervical cancer or ovarian cancer. A 52-year old patient with recurrent ovarian cancer, experienced two lines of chemotherapy failure, was orally administered with apatinib at a dose of 250mg daily from November 2015, got partial response (PR) after one month, PFS have not yet reach. A 43-year old female patient with advanced cervical cancer, experienced three lines of chemotherapy failure, was orally administered with apatinib at a dose of 250mg daily from September 2015, got PR with a PFS of 14 months. The toxicities associated with apatinib treatment was generally acceptable with 8 patients developed grade 3/4 toxicity. The most common adverse events in this study were hypertension(n = 17), hand-foot syndrome(n = 24), and mouth mucositis(n = 20). Conclusions: Apatinib monotherapy showed promising efficiency with tolerable toxicity for advanced/recurrent cervical and ovarian cancer patients who failed from two or more lines of chemotherapy.

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