Efficacy and safety of tivozanib in recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5538-5538 ◽  
Author(s):  
Wendy M Swetzig ◽  
John Robert Lurain ◽  
Emily Berry ◽  
Mario Javier Pineda ◽  
Shohreh Shahabi ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Median Number ◽  
Vegf Receptor ◽  
Open Label ◽  
Fallopian Tube Cancer ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Platinum Resistant

5538 Background: Tivozanib is a potent, selective pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor with a long half-life. This study assessed its activity in patients with recurrent, platinum-resistant ovarian cancer (OC), fallopian tube cancer (FTC) or primary peritoneal cancer (PPC). Methods: This open-label phase II study used a Simon’s two-stage design. Eligible patients had recurrent, platinum-resistant OC, FTC or PPC; ECOG PS of 0-1; normal end organ function; and measurable or detectable disease. There was no limit on the number of prior regimens. Treatment consisted of tivozanib 1.5 mg orally once daily (3 weeks on/1 week off). The primary endpoint was response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity assessment. If 1 partial response (PR) was observed in stage I [n = 12], enrollment proceeded to stage II. The null hypothesis was rejected for ≥ 4 responses in 30 patients. Results: Thirty-one patients were enrolled, and 30 were treated. Twenty-three had OC [76.67%], 5 FTC [16.67%] and 2 PPC [6.67%]. Twenty-six had measurable [86.67%] and 4 detectable disease [13.37%]. The median age was 60, and median number of prior regimens was 4 [range 1-9]. Four PRs [13.33%] were recorded. Twelve patients had stable disease (SD) [40%]. The clinical benefit rate (PR + SD) was 53%. Seven patients [23.33%] survived progression-free for > 6 mos. One patient continued treatment for > 2 yrs. The median PFS was 4 mos [range 1-25] and median OS was 8 mos [range 1-39]. There were no treatment-related deaths. Grade 3-4 related toxicities were hypertension [8], fatigue [3], fistula [2], hyponatremia [2], intestinal perforation, obstruction, stroke, proteinuria, hypomagnesemia, hypoalbuminemia, portal hypertension, nausea and anemia [1 each]. Frequent grade 1-2 related toxicities included fatigue [19], hypertension [13], anorexia [12], arthralgia [11], diarrhea [11], weight loss [10], hoarseness [8], headache [8] and nausea [7]. Exploratory analyses in tumor samples are ongoing. Conclusions: Tivozanib is active in patients with recurrent OC, FTC or PPC, without substantial toxicity, supporting its further development. Clinical trial information: NCT01853644.

Randomized, Open-Label, Phase III Study Comparing Patupilone (EPO906) With Pegylated Liposomal Doxorubicin in Platinum-Refractory or -Resistant Patients With Recurrent Epithelial Ovarian, Primary Fallopian Tube, or Primary Peritoneal Cancer

2012 ◽  
Vol 30 (31) ◽  
pp. 3841-3847 ◽  
Author(s):  
Nicoletta Colombo ◽  
Elzbieta Kutarska ◽  
Meletios Dimopoulos ◽  
Duk-Soo Bae ◽  
Izabella Rzepka-Gorska ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Significant Difference ◽  
Platinum Refractory

Purpose This study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. Patients and Methods Patients with three or fewer prior regimens were eligible if they had received first-line taxane/platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m2 intravenously every 3 weeks) or PLD (50 mg/m2 intravenously every 4 weeks). Results A total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm. Conclusion Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.

Retrospective review: re-treatment of patients with ovarian cancer with carboplatin after platinum resistance

2005 ◽  
Vol 15 (2) ◽  
pp. 209-216 ◽  
Author(s):  
H. T. See ◽  
R. S. Freedman ◽  
A. P. Kudelka ◽  
T. W. Burke ◽  
D. M. Gershenson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Median Overall Survival ◽  
Median Number ◽  
Platinum Resistance ◽  
Time To Progression ◽  
Fallopian Tube Cancer ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Free Interval ◽  
Platinum Resistant

The objective of the analysis was to determine the effectiveness of re-treating patients with ovarian cancer, primary peritoneal cancer, and fallopian tube cancer with carboplatin after being deemed platinum resistant. From a database period January 1, 1996, to December 12, 2002, 34 patients were identified who received nonplatinum agents before resuming treatment with carboplatin. The median age was 65 years, and a median of two nonplatinum chemotherapy (range 1–5) prior to re-treatment with carboplatin was received. The median platinum-free interval from the time platinum was last received to re-treatment with carboplatin was 15.2 months (95% confidence interval [CI] 12.6–17.9; range 6.2–47.0). A median number of four cycles of carboplatin (range 1–11) was received. Two patients (5.9%) achieved partial response, while 21 patients (61.7%) achieved stable disease. The median time to progression for these 23 patients after re-treatment with carboplatin was 5.7 months (95% CI 5.2–6.3; range 1.8–15.3). Twenty-seven patients have died, and all patients have progressed. Seven patients are still receiving salvage therapy. The median overall survival from the time deemed to be platinum resistant is 23.2 months (95% CI 20.1–26.4). Patients who have been deemed platinum resistant may still benefit from platinum re-treatment after an interval of treatment with nonplatinum agents

Results from a phase II randomized, placebo-controlled, double-blind trial suggest improved PFS with the addition of pertuzumab to gemcitabine in patients with platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5507-5507 ◽  
Author(s):  
S. Makhija ◽  
D. Glenn ◽  
F. Ueland ◽  
M. Gold ◽  
D. Dizon ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Phase Ii ◽  
Survival Data ◽  
Single Agent ◽  
Erbb Receptors ◽  
Clinical Activity ◽  
Fallopian Tube Cancer ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Platinum Resistant

5507 Background: Pertuzumab (P) is a humanized monoclonal antibody that blocks the ability of HER2 to heterodimerize with other HER/ErbB receptors. As a single agent, P has demonstrated clinical activity in relapsed/refractory epithelial ovarian cancer (EOC). Since platinum-resistant (CDDP-R) EOC remains a difficult disease to treat, this phase II study was conducted to determine if addition of P to gemcitabine (G) would improve results. Methods: Patients with CDDP-R EOC (including ovarian, fallopian tube, or primary peritoneal cancer) who had received up to one prior treatment for CDDP-R disease were randomized to Gem 800 mg/m2 on D1, 8 of a 21-day cycle ± P or placebo (pl). P was given as an 840 mg initial dose followed by 420mg IV every 3 weeks. Tumor response was assessed by RECIST every 6 weeks using GOG criteria. The primary endpoint was progression free survival (PFS). Results: One hundred thirty patients (n = 65 each treatment cohort) were treated. Clinical characteristics were balanced between the treatment groups. Pts received a median of 2 prior regimens (range 1–6) for EOC. Based on 83 events, the adjusted hazard ratio for PFS was 0.67 (95% CI: 0.43–1.02), p =0.06 in favor of P+Gem. The median PFS was 3.0 months (0–8.7 months) vs. 2.6 months (0–9+ months), and the PFS rate at 4 months was 49% vs. 34% in the P+Gem and Gem/pl arms, respectively. The most common AEs increased in the P-treated pts were fatigue, nausea, diarrhea, back pain, Gr 3–4 neutropenia, rash, headache, stomatitis, epistaxis, and rhinorrhea. Clinically significant CHF was reported in one patient in the pertuzumab cohort. There was no imbalance in the LVEF results between treatment arms. One patient who received pertuzumab + gemcitabine experienced an adverse event that resulted in death (hemolytic-uremic syndrome). Conclusions: These data suggest that pertuzumab may add activity to gemcitabine as reflected by improvements in PFS in patients with CDDP-R ovarian, primary peritoneal, or fallopian tube cancer. Survival data will be presented at ASCO. No significant financial relationships to disclose.

FORWARD I (GOG 3011): A randomized phase 3 study to evaluate the safety and efficacy of mirvetuximab soravtansine (IMGN853) versus chemotherapy in adults with folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian cancer (EOC), primary peritoneal cancer, or primary fallopian tube cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS5607-TPS5607 ◽  
Author(s):  
Kathleen N. Moore ◽  
Ignace Vergote ◽  
Ana Oaknin ◽  
Nicoletta Colombo ◽  
Susana N. Banerjee ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Folate Receptor ◽  
Single Agent ◽  
Objective Response ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase 3 ◽  
Fallopian Tube Cancer ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Platinum Resistant

TPS5607 Background: Elevated FRα expression is characteristic of a number of solid tumors, including EOC, thereby providing an attractive candidate for targeted therapeutic approaches. Mirvetuximab soravtansine is an antibody-drug conjugate (ADC), comprising a FRα-binding antibody linked to the tubulin-disrupting maytansinoid DM4, that has shown single agent clinical activity and a favorable safety profile in an ongoing, first-in-human phase 1 trial (NCT01609556). Methods: FORWARD I is a randomized phase 3 study designed to evaluate the efficacy of mirvetuximab soravtansine compared with that of standard-of-care chemotherapy in adult patients with platinum-resistant EOC, primary peritoneal cancer, or fallopian tube cancer. Confirmation of FRα positivity by immunohistochemistry (medium or high expression; ≥ 50% of cells with at least moderate staining intensity) and ≤ 3 prior lines of therapy are required for inclusion. A maximum of 333 patients are expected to be recruited. Patients will be randomized 2:1 to Arm 1 (intravenous mirvetuximab soravtansine at a dose of 6.0 mg/kg, calculated using adjusted ideal body weight, on Day 1 of a 21-day cycle) or Arm 2 (investigators’ choice chemotherapy: paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary efficacy endpoint is progression-free survival (PFS; by blinded independent central review) and secondary endpoints include objective response rate, quality of life, overall survival, safety and tolerability, and duration of response. The first patient was enrolled in January 2017. Clinical trial information: NCT02631876.

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