L-MOCA: An open-label study of olaparib maintenance monotherapy in platinum-sensitive relapsed ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17526-e17526
Author(s):  
Qing-lei Gao ◽  
Jianqing Zhu ◽  
Weidong Zhao ◽  
Yi Huang ◽  
Ruifang An ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Brca Mutation ◽  
Progression Free Survival ◽  
Primary Analysis ◽  
Open Label ◽  
Platinum Sensitive ◽  
Kaplan Meier ◽  
Platinum Based Chemotherapy ◽  
Full Analysis

e17526 Background: In patients with platinum-sensitive recurrent serous ovarian cancer, maintenance monotherapy with the poly (ADP-ribose) polymerase inhibitor (PARPi) olaparib, significantly improves progression-free survival (PFS) versus placebo. This is the first study to evaluate the efficacy and tolerability of the olaparib (Lynparza), an oral PARPi, in patients with platinum-sensitive relapsed (PSR) ovarian cancer, carried out exclusively in Asia. Methods: In this open-label, single arm trial, patients with PSR high grade epithelial ovarian cancer who had received ≥2 previous lines of platinum-based chemotherapy with a response, were enrolled from 28 centres in China and Malaysia. All patients received oral olaparib (300 mg) tablet twice daily until disease progression or unacceptable toxicity. The primary endpoint was PFS assessed by investigator according to RECIST 1.1 criteria. Secondary endpoints included time to TFST, PFS2, TSST, OS, and safety endpoints included adverse events (AEs). Subgroup analysis of PFS was examined by BRCA status. Data were summarized by descriptive statistics; time-to-event endpoints were analyzed using Kaplan-Meier method. Primary analysis was performed when 60% of PFS events had been achieved. Results: Between 2018 and 2020, the 224 patients recruited into this study received oral olaparib (full analysis set). 224 patients (91.5% from China and 8.5% from Malaysia) provided BRCA mutation status by blood and tissue testing. 47.3% patients were BRCAm, 41.1% patients were gBRCAm,52.2% patients were BRCAwt and 0.4% patients were BRCA unknown. 35.7% patients had received ＞2 lines of chemotherapy. At data cut-off (Dec 25th, 2020), 139 patients had disease progression; median PFS (mPFS) was 16.1 (95% CI 13.3-18.3) m in all patients. The mPFS was 21.2m, 21.4m and 11.0m in BRCAm, gBRCA and BRCAwt subgroups, respectively. The overall incidence of any AE and SAE was 99.1% and 25.4%, respectively. There were 9.4% patients who discontinued therapy due to the treatment related AE. The most common AEs were anemia, nausea and vomiting. Conclusions: The L-MOCA study demonstrates olaparib maintenance treatment is effective and well tolerated in Asian PSR ovarian cancer patients regardless of BRCA status. Clinical trial information: NCT03534453. [Table: see text]

Olaparib treatment (Tx) in patients (pts) with platinum-sensitive relapsed ovarian cancer (PSR OC) by BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: Overall survival (OS) results from the phase II LIGHT study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5515-5515
Author(s):  
Cara Amanda Mathews ◽  
Fiona Simpkins ◽  
Karen Anne Cadoo ◽  
Ying L Liu ◽  
Diane M. Provencher ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Brca Mutation ◽  
Primary Analysis ◽  
Platinum Sensitive ◽  
Kaplan Meier ◽  
Platinum Based Chemotherapy ◽  
Starting Dose ◽  
Unacceptable Toxicity

5515 Background: LIGHT (NCT02983799) evaluated olaparib Tx in pts with PSR OC in cohorts with known BRCAm and HRD status. We report the final OS analyses. Methods: We conducted anopen-label, non-randomized, multicenter study of pts with PSR OC and ≥1 prior line of platinum-based chemotherapy (CTx). Pts were assigned to one of 4 cohorts: germline (g) BRCAm; somatic (s) BRCAm; HRD +ve (non-BRCAm); and HRD -ve. Genomic instability score (GIS) and gBRCAm status were determined by Myriad myChoice and BRACAnalysis CDx tests, respectively. HRD +ve tumors were defined by a GIS ≥42. Pts received olaparib Tx (starting dose 300 mg bid) until disease progression or unacceptable toxicity. OS was a secondary endpoint and was analyzed at 12 months (mo) after the primary analysis and 18 mo after the last pt was enrolled. Safety was assessed in pts who received ≥1 dose. Results: Data cut-off (DCO) was Aug 27, 2020. Of 272 enrolled pts, 271 received olaparib; of these, 270 had measurable disease at baseline and were included in efficacy analyses (Table). At DCO, 40% of pts had died (maturity) with a median follow-up in censored pts of 26.3 mo. Kaplan–Meier 18-mo OS rates were 86%, 88%, 79%, and 60% in the gBRCAm, sBRCAm, HRD +ve (non-BRCAm), and HRD -ve cohorts, respectively. Platinum-based CTx was the most common first subsequent Tx and was received by 39% pts after olaparib discontinuation. At DCO, the median duration of Tx was 7.4 mo and 244 pts had discontinued treatment, mainly due to disease progression (72%); 5% discontinued due to treatment-emergent adverse events (TEAEs). The only TEAE leading to discontinuation in >1 pt was nausea (2 pts). Serious TEAEs were reported in 25% of pts. The most common serious TEAE was small intestinal obstruction (6%). Three adverse events of special interest occurred, each in 1 pt (<1%): acute myeloid leukemia (post discontinuation), pneumonitis, and pulmonary fibrosis. Conclusions: In the final OS analysis, 18-mo OS ranged from 60–88% across the 4 cohorts. Consistent with the primary analysis, the 18-mo OS rate was highest in the BRCAm cohorts (similar OS in g and sBRCAm); among pts without a BRCAm, 18-mo OS was highest in the HRD +ve cohort. No new safety signals were observed compared with the primary analysis and with prior olaparib studies. Clinical trial information: NCT02983799. [Table: see text]

Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase IIIb OPINION primary analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5545-5545
Author(s):  
Andres Poveda ◽  
Stephanie Lheureux ◽  
Nicoletta Colombo ◽  
David Cibula ◽  
Kristina Lindemann ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Progression Free Survival ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Phase Iii ◽  
Primary Analysis ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Phase Iiib ◽  
Grade 3

5545 Background: In the Phase II Study 19 trial (NCT00753545; Ledermann et al Lancet Oncol 2014), maintenance olaparib improved progression-free survival (PFS) vs placebo in PSR OC pts, including non-BRCAm pts. A significant PFS benefit was also seen with maintenance olaparib vs placebo in gBRCAm PSR OC pts in the Phase III SOLO2 trial (NCT01874353; Pujade-Lauraine et al Lancet Oncol 2017). To investigate olaparib maintenance monotherapy in non-gBRCAm PSR OC pts who had received ≥2 prior lines of platinum-based chemotherapy (PBC), we performed the Phase IIIb, single-arm, OPINION study (NCT03402841). Methods: Pts had high-grade serous or endometrioid OC and were in complete response (CR) or partial response (PR) to PBC. Pts received maintenance olaparib (tablets; 300 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). Secondary endpoints included PFS by homologous recombination deficiency (HRD) and somatic BRCA mutation (sBRCAm) status determined by central Myriad tumor and germline testing; and time to first subsequent treatment (TFST). The primary analysis was planned for 18 months (mo) after the last patient was enrolled. Results: 279 pts were enrolled from 17 countries (mean age: 64 years); 253 pts (90.7%) were confirmed non-gBRCAm. At data cut-off (Oct 2, 2020), median PFS was 9.2 mo (95% CI 7.6–10.9), with 210 PFS events (75.3% maturity). 65.3%, 38.5% and 24.3% of pts were progression-free (PF) at 6, 12 and 18 mo, respectively. The Table shows PFS in key subgroups. Median TFST was 13.9 mo (95% CI 11.5–16.4). Median exposure to olaparib was 9.4 mo (range 0.0–31.9). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 29.0% of pts and serious TEAEs in 19.7% of pts. TEAEs led to dose interruption, dose reduction and treatment discontinuation in 47.0%, 22.6% and 7.5% of pts, respectively. Conclusions: Our findings support the use of olaparib maintenance therapy in non-gBRCAm PSR OC pts, consistent with our interim analysis and previous trials in this setting. Clinical trial information: NCT03402841. [Table: see text]

Olaparib treatment in patients (pts) with platinum-sensitive relapsed (PSR) ovarian cancer (OC) by BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: Phase II LIGHT study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6013-6013 ◽  
Author(s):  
Karen Anne Cadoo ◽  
Fiona Simpkins ◽  
Cara Amanda Mathews ◽  
Nashwa Kabil ◽  
James Bennett ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Randomized Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Primary Analysis ◽  
Open Label ◽  
Platinum Sensitive ◽  
Grade 3 ◽  
Platinum Chemotherapy

6013 Background: In Study 19 (NCT00753545), olaparib capsules demonstrated improvement in progression-free survival (PFS) vs placebo in the PSR OC maintenance setting, irrespective of BRCAm status (Ledermann et al. Lancet Oncol 2014). LIGHT is the first prospective study to evaluate olaparib tablet treatment in PSR OC pts by BRCAm and HRD status. Methods: This is an open-label, non-randomized study (NCT02983799) that assessed efficacy and safety of olaparib monotherapy (300 mg BID) in pts with PSR, high-grade serous/endometrioid epithelial OC and ≥1 prior line of platinum chemotherapy. Pts were assigned to one of four cohorts: germline (g) BRCAm; somatic (s) BRCAm; HRD+ve (non-BRCAm); HRD–ve; by Myriad BRACAnalysis CDx and myChoice tests. HRD+ve was a score ≥42. Primary endpoint was objective response rate (ORR). Secondary endpoints included: disease control rate (DCR) and investigator-assessed PFS (RECIST v1.1). Primary analysis was to be ~6 months (mo) after the last pt was enrolled. Results: Data cut off was 8/27/19. Of 271 pts treated (median of 31.7 weeks [2.1–96.0]), 270 had measurable disease at baseline and were included in efficacy analyses (Table). The most common treatment-emergent adverse events (AEs) were nausea (66%) and fatigue (62%).Serious AEs and Grade ≥3 AEs were experienced by 25% and 44% of pts, respectively. AEs leading to olaparib dose interruptions, reductions and discontinuations occurred in 33%, 24% and 4% of pts, respectively. Conclusions: Olaparib treatment demonstrated activity across all cohorts. As observed in the maintenance setting, similar efficacy was seen in the gBRCAm and sBRCAm cohorts. For non-BRCAm pts, longer median PFS and higher ORR were observed in the HRD+ve cohort. Olaparib treatment was well tolerated with no new safety signals identified and a safety profile consistent with that seen in the PSR and first-line settings. Clinical trial information: NCT02983799. [Table: see text]

A phase III study comparing single-agent olaparib or the combination of cediranib and olaparib to standard platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6003-6003 ◽  
Author(s):  
Joyce F. Liu ◽  
Mark F. Brady ◽  
Ursula A. Matulonis ◽  
Austin Miller ◽  
Elise C. Kohn ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Primary Endpoint ◽  
Parp Inhibitor ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
High Grade ◽  
Primary Analysis ◽  
Open Label ◽  
Platinum Based Chemotherapy

6003 Background: Combination cediranib (C) and olaparib (O) improved progression-free survival (PFS) in patients (pts) with relapsed platinum (plat)-sensitive high-grade ovarian cancer (ovca) compared to O alone in a Phase 2 trial (NCT01116648). We conducted this randomized, open-label Phase 3 trial (NCT02446600) to assess whether combination C+O, or O alone, was superior to standard of care (SOC) plat-based therapy in relapsed plat-sensitive ovca. Methods: Eligible pts had recurrent plat-sensitive [ > 6-month plat-free interval (PFI)] high-grade serous or endometrioid, or BRCA-related, ovca. One prior non-plat therapy and unlimited prior plat-therapies were allowed; prior anti-angiogenics in the recurrent setting or prior PARP inhibitor were exclusions. Pts were randomized 1:1:1 to SOC (carboplatin/paclitaxel; carboplatin/gemcitabine; or carboplatin/liposomal doxorubicin), O (300mg twice daily), or C+O (C 30mg daily + O 200mg twice daily). Randomization was stratified by g BRCA status, PFI (6-12 vs > 12 months), and prior anti-angiogenic therapy. Target sample size was 549 pts; primary analysis occurred 2 years after the last pt enrolled. The primary endpoint was PFS. Type 1 error = 0.025 was controlled by a gatekeeping hierarchy that assessed C+O vs SOC, then O alone vs SOC, and finally C+O vs O. All maintenance therapy was prohibited. Results: Between 4FEB2016 and 13NOV2017, 565 pts enrolled (187 SOC, 189 O, 189 C+O), and 528 pts initiated treatment (166 SOC, 183 O, 179 C+O). 23.7% of patients had g BRCAmut. Median follow-up was 29.1 months. 53 pts on SOC initiated non-protocol therapy (predominantly PARP inhibitor maintenance) before disease progression. The hazard ratio (HR) for PFS was 0.856 (95% CI 0.66-1.11, p = 0.08, 1-tail) between C+O and SOC and 1.20 (95% CI 0.93-1.54) between O and SOC, with median PFS of 10.3, 8.2, and 10.4 months for SOC, O, and C+O, respectively. Response rates were 71.3% (SOC), 52.4% (O), and 69.4% (C+O). In gBRCA pts, HR for PFS was 0.55 (95% CI 0.73-1.30) for C+O vs SOC, and 0.63 (95% CI 0.37-1.07) for O vs SOC. In non-g BRCA pts, HR for these comparisons was 0.97 (95% CI 0.73-1.30) and 1.41 (1.07-1.86). No OS differences between arms were observed at 44% events. Pts receiving C+O (vs SOC) had more frequent Grade 3 or higher gastrointestinal (30.1% vs 8.4%), hypertension (31.7% vs 1.8%), and fatigue events (17.5% vs 1.8%). Conclusion: C+O demonstrated similar activity to SOC in relapsed plat-sensitive ovca but did not meet the primary endpoint of improved PFS. Clinical trial information: NCT02446600.

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design

2019 ◽  
Vol 15 (32) ◽  
pp. 3651-3663
Author(s):  
Andres M Poveda ◽  
Richard Davidson ◽  
Christopher Blakeley ◽  
Alvin Milner
Keyword(s):  
Ovarian Cancer ◽  
Brca2 Mutation ◽  
Progression Free Survival ◽  
Open Label ◽  
Brca Mutations ◽  
Clinical Trial Registration ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Phase Iiib

The poly(ADP-ribose) polymerase inhibitor olaparib (Lynparza™) is approved for maintenance treatment of platinum-sensitive relapsed ovarian cancer. OPINION is a single-arm, open-label, multicenter, Phase IIIb study to assess the efficacy and safety of olaparib tablet maintenance therapy in women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer without a germline BRCA1 or BRCA2 mutation. Eligible patients should have received ≥2 prior lines of platinum-based chemotherapy and be in complete or partial response following their most recent course or have no evidence of disease. Patients will receive olaparib tablets (300 mg twice daily) until disease progression, unacceptable toxicity or another discontinuation criterion. The primary end point is investigator-assessed progression-free survival; secondary end points include progression-free survival according to tumor homologous recombination deficiency status. Clinical trial registration: NCT03402841.

Overall survival and updated progression-free survival results from a randomized phase 2 trial comparing the combination of olaparib and cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5535-5535 ◽  
Author(s):  
Joyce F. Liu ◽  
William Thomas Barry ◽  
Michael J. Birrer ◽  
Jung-min Lee ◽  
Ronald J. Buckanovich ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Free Survival ◽  
Angiogenic Therapy ◽  
Platinum Sensitive

5535 Background: We previously reported that the combination of cediranib (ced) and olaparib (olap) improved progression-free survival (PFS) and overall response rates (ORR) in women with recurrent platinum-sensitive (plat-sens) high-grade serous (HGS) or BRCA-related ovarian cancer (OvCa) (NCT 01116648). We conducted an updated PFS and overall survival (OS) analysis. 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. PFS was defined as time from randomization to radiographic progression or death. OS was defined as time from randomization to death. 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). As of Dec 21, 2016, 67 pts had a PFS event, and 52 pts had an OS event. Updated median PFS was 8.2 mos for Olap and 16.5 mos for Ced/Olap (HR 0.50, 95% CI 0.30-0.83, p=0.007). Median OS was 33.3 mos for Olap and 44.2 mos for Ced/Olap (HR 0.64, 95% CI 0.36-1.11, p=0.11). Within known germline BRCA mut carriers, updated PFS was 16.5 vs 16.4 mos (HR 0.75, p=0.42), and OS was 40.1 vs 44.2 mos (HR 0.79, p=0.55) for Olap and Ced/Olap, respectively. In pts without known germline BRCA mut, updated PFS was 5.7 vs 23.7 mos (HR 0.32, p=0.002), and OS was 23.0 vs 37.8 mos (HR 0.48, p=0.074). Conclusions: Updated PFS results consistently demonstrated that Ced/Olap significantly extended PFS compared to Olap in the overall population of women with plat-sens OvCa. In this Phase 2 study not powered to detect OS diferences, there was a trend towards OS improvement with Ced/Olap, particularly in pts without a known germline BRCA mutation. Results from ongoing studies of this oral combination in OvCa are of clinical interest. Clinical trial information: NCT 01116648.

Cediranib in combination with olaparib in patients without a germline BRCA1/2 mutation with recurrent platinum-resistant ovarian cancer: Phase IIb CONCERTO trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6056-6056
Author(s):  
Jung-min Lee ◽  
Richard G. Moore ◽  
Sharad A. Ghamande ◽  
Min S. Park ◽  
John Paul Diaz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Response Rate ◽  
Brca Mutation ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Repair Gene ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy

6056 Background: A Phase I trial (NCT01116648) of cediranib (cedi) in combination with olaparib (ola) (cedi + ola) demonstrated an overall response rate of 44% in patients (pts) with recurrent ovarian cancer (OC), including pts without a deleterious or suspected deleterious gBRCAm (non-gBRCAm; Liu et al. Eur J Cancer 2013). The subsequent Phase II trial (NCT01116648) showed significant improvement in progression-free survival (PFS) with cedi + ola versus ola monotherapy in recurrent platinum-sensitive OC pts, notably in non-gBRCAm pts (Liu et al. Lancet Oncol 2014). We report data from the Phase IIb, single-arm, open-label CONCERTO study investigating cedi + ola in non-gBRCAm pts with recurrent platinum-resistant OC who had received ≥3 previous lines of therapy for advanced OC (NCT02889900). Methods: Pts with disease progression <6 months from the last receipt of platinum-based chemotherapy received cedi tablets (30 mg once daily) plus ola tablets (200 mg twice daily) until progression or unacceptable toxicity. gBRCAm pts were ineligible. Primary endpoint: objective response rate (ORR) by independent central review (ICR; RECIST 1.1). Key secondary endpoints: PFS and safety. Results: 60 pts from the USA were included (median age: 64.5 years; median number of previous systemic treatment regimens: 4 [range: 2–9]; previous bevacizumab: 53). All pts had high-grade OC (90% serous; 3.3% clear cell; 3.3% endometrioid; 3.3% other). 7% of pts had tumor BRCA2 (confirmed somatic) mutations, 80% of pts had no tumor BRCA mutation (non-tBRCAm) and 13% of pts were not evaluable for tBRCAm. Five (8%) pts who were non-tBRCAm carried somatic homologous recombination repair gene mutations (FoundationOne Clinical Trial Assay, Foundation Medicine, Inc). The Table shows results of key endpoints. Most common grade ≥3 adverse events (AEs) that occurred in pts were hypertension (30%), fatigue (22%) and diarrhea (13%). 37% of pts reported serious AEs, of which nausea (7%) was most common. Dose interruptions, reductions and discontinuations were caused by AEs in 55%, 18% and 18% of pts, respectively, who received cedi + ola. Conclusions: Cedi + ola showed evidence of antitumor activity in heavily pretreated non-gBRCAm pts with recurrent platinum-resistant OC. Toxicity was manageable with dose modifications. Clinical trial information: NCT02889900. [Table: see text]

Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission

2021 ◽  
pp. ijgc-2020-002239
Author(s):  
Oren Smaletz ◽  
Gustavo Ismael ◽  
Maria Del Pilar Estevez-Diz ◽  
Ivana L O Nascimento ◽  
Ana Luiza Gomes de Morais ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Monoclonal Antibody ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Lewis Y

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.MethodsThis single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.ResultsTwenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).ConclusionsHu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.Trial registrationNCT01137071.

Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer

2010 ◽  
Vol 28 (19) ◽  
pp. 3107-3114 ◽  
Author(s):  
Bradley J. Monk ◽  
Thomas J. Herzog ◽  
Stanley B. Kaye ◽  
Carolyn N. Krasner ◽  
Jan B. Vermorken ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Performance Status ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Hazard Ratio ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Hand Foot Syndrome

PurposeThe objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin (PLD) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy.Patients and MethodsWomen ≥ 18 years, stratified by performance status (0 to 1 v 2) and platinum sensitivity, were randomly assigned to receive an intravenous infusion of PLD 30 mg/m2followed by a 3-hour infusion of trabectedin 1.1 mg/m2every 3 weeks or PLD 50 mg/m2every 4 weeks. The primary end point was progression-free survival (PFS) by independent radiology assessment.ResultsPatients (N = 672) were randomly assigned to trabectedin/PLD (n = 337) or PLD (n = 335). Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD (hazard ratio, 0.79; 95% CI, 0.65 to 0.96; P = .0190). For platinum-sensitive patients, median PFS was 9.2 months v 7.5 months, respectively (hazard ratio, 0.73; 95% CI, 0.56 to 0.95; P = .0170). Overall response rate (ORR) was 27.6% for trabectedin/PLD v 18.8% for PLD (P = .0080); for platinum-sensitive patients, it was 35.3% v 22.6% (P = .0042), respectively. ORR, PFS, and overall survival among platinum-resistant patients were not statistically different. Neutropenia was more common with trabectedin/PLD. Grade 3 to 4 transaminase elevations were also more common with the combination but were transient and noncumulative. Hand-foot syndrome and mucositis were less frequent with trabectedin/PLD than with PLD alone.ConclusionWhen combined with PLD, trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer.

New biomarkers to predict platinum resistance in ovarian cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17085-e17085
Author(s):  
Oana Trifanescu ◽  
Laurentia Minea Gales ◽  
Maria Iuliana Gruia ◽  
Bianca Andreea Gusoiu ◽  
Florina Torliceanu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Roc Curve ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Initial Response ◽  
Platinum Resistance ◽  
Platinum Sensitive ◽  
Platinum Salts ◽  
Platinum Based Chemotherapy

e17085 Background: Epithelial ovarian cancer is the second most common gynecologic malignancy and is characterized by the highest mortality of all gynecological cancers. Despite of initial response, platinum resistance develops and contributes to the poor outcome of advanced stage ovarian cancer patients. The aim of the study was to identify biomarkers helpful in predicting treatment response to platinum salts. Methods: Forty eight patients with advanced ovarian (stage II, III and IV) cancer were prospectively enrolled between 2014 and 2017. All patients underwent surgery followed by platinum-based chemotherapy. Serum reactive oxygen species parameters such as malondialdehyde, ceruloplasmine, and serum VEGF were measured before each cycle of chemotherapy. Results: Mean age at diagnostic was 51.3 +/- 8.1 years, (range 42 - 78). Median follow up was 39 months (range 12-56). Twenty tree percent were platinum resistance. Median progression free survival was 22 months and estimated median overall survival was 84 months, 77% of patients being alive at 3 years. VEGF levels were significantly higher in patients with platinum resistance disease (1210 pg/ml) compare to platinum sensitive (mean VEGF levels 945pg/ml, p = 0.0003). We used a ROC curve to estimate the sensitivity and specificity of VEGF as a predictor to platinum response and find out that the aria under the curve (AUC) was 0.874, p = 0.003, 95% CI 0.734-1 and cut-off value (80% sensibility, 80% specificity) was 1085pg/ml. Malondialdehyde levels were statistically significant higher in patients with platinum resistance disease (mean value 11.1 μmol/100 ml vs. 7.4 μmol/100 ml in platinum sensitive, p = 0.02. The ROC curve for malondialdehyde identify an aria under the curve of 0.818, p = 0.0001 and CI 95% (0.744-0.893) and a cut-off value of 7.74 μmol/100 ml to estimate with 81.3% sensitivity and 64% specificity platinum response validating this bio markers as predicting platinum response. For Ceruloplasmine AUC was 0.706, p = 0.0001, 95% CI (0.617,-0.796). Conclusions: Malondialdehyde, ceruloplasmine and VEGF can estimate with precision the resistance to platinum salts in advanced ovarian cancer patients.

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