Eribulin: A Novel Cytotoxic Chemotherapy Agent (June).

Eribulin: A Novel Cytotoxic Chemotherapy Agent (June)

Ann Pharmacother. 2012 May 22;

Abstract
OBJECTIVE:To review the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of eribulin (Halaven).

....Eribulin has also shown activity in Phase 2 studies in other types of cancers, such as non-small cell lung cancer, prostate cancer, urothelial cancer, soft tissue sarcomas, and platinum-susceptible ovarian, fallopian tube, or peritoneal cancers........

open access: JCO - OCEANS: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Chemotherapy With or Without Bevacizumab in Patients With Platinum-Sensitive Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

OCEANS: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Chemotherapy With or Without Bevacizumab in Patients With Platinum-Sensitive Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

• Submitted January 26, 2012; accepted
  February 17, 2012; published online
  ahead of print at www.jco.org on April
  23, 2012.
• Supported by Genentech.
• Presented in part at the 47th Annual
  Meeting of the American Society of
  Clinical Oncology, June 3-7, 2011,
  Chicago, IL.

Table 1. Baseline Patient Demographics and Disease Characteristics: 
(see actual table for further details; see other tables for adverse/safety event comparisons; )

Histology subtype #'s

Serous 202
Mucinous 1
Endometrioid 16
Transitional cell 2
Clear cell 6
Mixed 5
Other 10



 The limitations of OCEANS include a lack of quality-of-life data
and specimen collection for biomarker analysis. The strengths of
OCEANS, however, lie in the robustness of the primary end point,
with strict adherence to RECIST-defined progression and its supportive
IRC analysis, and to the schedule of assessments. The median
increase of 4 months in PFS is well above the frequency of radiologic
reassessments (9 weeks).24,25 TheOCEANS data demonstrate that GC
plus BV followed by BV until progression provides benefit over GC
alone in ROC. OCEANS, GOG 218, and ICON7 represent three
positive phase III trials of BVadded to chemotherapy in the treatment
of ovarian cancer.

open access: Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer — NEJM

Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer — NEJM

......"We evaluated the efficacy of olaparib monotherapy as maintenance treatment in patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer who had had a response to their most recent platinum-based chemotherapy......"

In conclusion, the results from this randomized, phase 2 study show that maintenance treatment with olaparib was associated with a significant improvement in progression-free survival among patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer. However, at the interim analysis, this did not translate into an overall survival benefit. As of this writing, 21% of the patients were still receiving olaparib (and 3% were still receiving placebo), which indicates that the disease is controlled for a prolonged period in some patients.

Morphotek®, Inc. Announces Completion of Enrollment in the FAR-131 Trial for Relapsed Ovarian Cancer

Morphotek®, Inc. Announces Completion of Enrollment in the FAR-131 Trial for Relapsed... -- EXTON, Pa., March 27, 2012 /PRNewswire/ --

Clinical Study Seeks to Evaluate Farletuzumab in Combination with Standard of Care in First-Relapse Patients with Platinum-Sensitive Ovarian Cancer

EXTON, Pa., March 27, 2012 /PRNewswire/ -- Morphotek®, Inc., a subsidiary of Eisai Inc., announced today it has completed enrollment of the FAR-131 clinical trial. The study is a pivotal Phase 3 randomized trial of farletuzumab in first-relapsed patients with platinum-sensitive ovarian cancer. Farletuzumab is a humanized monoclonal antibody that targets folate receptor alpha (FRA), which is expressed on the majority of non-mucinous epithelial ovarian cancers as well as a subset of other carcinomas.
The trial is designed as a three-armed, randomized, double-blinded, controlled study in patients with platinum-sensitive ovarian cancer who relapse after first-line treatment with standard of care. FAR-131 tests the ability of farletuzumab at two different dosages in combination with second-line standard-of-care (carboplatin or cisplatin plus paclitaxel or docetaxel) for patients with platinum-sensitive disease to improve progression-free survival as compared to those treated with standard-of-care and placebo. Secondary endpoints include improvements in overall survival, objective tumor responses and the number of patients exhibiting longer second remission periods as compared to their primary remission.

FAR-131 was initiated in March 2009, and has reached its randomization target of 1080 patients at clinical sites in 30 countries located in North America, South America, Europe, Asia, Australia and the Middle East.

Farletuzumab is a monoclonal antibody that binds to and blocks the function of FRA, a cell surface protein on tumor cells that confers a growth advantage to tumorigenic ovarian cells in vitro. FRA has been demonstrated by several independent studies to be expressed on a variety of cancer types. The antibody also is being tested in a randomized Phase 2 study to assess its effect in patients with FRA⁺ non-small-cell lung adenocarcinoma in combination with standard of care in first-line therapy.

Further information on the clinical study can be found at www.clinicaltrials.gov, study number NCT00849667.

Found 1 study with search of:

NCT00849667

 

	Active, not recruiting	Efficacy and Safety of MORAb-003 in Subjects With Platinum-sensitive Ovarian Cancer in First Relapse Condition: Ovarian Cancer Interventions: Drug: MORAb-003 (farletuzumab);   Drug: 0.9% Saline

abstract: Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy

Objective

To evaluate the predictive power of serum CA-125 changes in the management of patients under going neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC).

Methods

Using the Cancer Registry databases from our institutions, a retrospective review of patients with FIGO stage IIIC and IV EOC who were treated with platinum-based NACT-IDS between January 2006 and December 2009 was conducted. Demographic data, CA-125 levels, radiographic data, chemotherapy, and surgical-pathologic information were obtained.

Results

One hundred-three patients with stage IIIC or IV EOC met study criteria. Median number of neoadjuvant cycles was 3. Ninety-nine patients (96.1%) were optimally cytoreduced. Forty-seven patients (47.5%) had resection to no residual disease (NRD). The median CA-125 at diagnosis and before interval debulking was 1749 U/mL and 161 U/mL, respectively.

Comparing patients with NRD (no residual disease)  v. optimal macroscopic disease (OMD), there was no statistical difference in the mean CA-125 at diagnosis (1566 U/mL v. 2077 U/mL, p = 0.1).

There was a significant difference in the mean CA-125 prior to interval debulking, 92 v. 233 U/mL (p = 0.001).

In the NRD group, 38 patients (80%) had preoperative CA-125 ≤ 100 U/mL compared to 33 patients (63.4%) in the OMD group (p = 0.04).

Conclusions

 Patients who undergo NACT-IDS (neoadjuvant chemotherapy followed by interval debulking surgery) achieve a high rate of optimal cytoreduction. In our series, after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of ≤ 100 U/mL were highly likely to be cytoreduced to no residual disease.

Highlights

► Patients with advanced ovarian cancer treated with neoadjuvant chemotherapy have high rates of optimal cytoreduction.
► Preoperative CA-125 < 100 may indicate a high probability of debulking to no gross residual disease.
► A drop of > 80% in CA-125 during neoadjuvant treatment may suggest platinum sensitive disease.

Sanofi preps for new pivotal trial of a blockbuster hopeful - Iniparib/phase 11/platinum sensitive

Chemotherapy Options in the Management of Platinum-Sensitive Recurrent Ovarian Cancer

Note: registration required to view (free) SPECIAL EDITION / EDUCATIONAL REVIEWS

ISSUE: AUGUST, 2010 | VOLUME: 05:08 Chemotherapy Options in the Management of Platinum-Sensitive Recurrent Ovarian Cancer

Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse

Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse  
ABSTRACT  

Purpose This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC).  

Patients and Methods Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m2) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m2) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival.  

Results Overall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.  

Conclusion To our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.

Clinical Update - Ovarian Cancer (commentary - Australia)- Secondary cytoreductive surgery in the management of platinum-sensitive recurrent epithelial ovarian cancer ...

Note: abstract plus commentary from Australian specialist/Associate Professor Jim Nicklin; includes reference to upcoming trial results

Feasibility of extension of platinum-free interval with weekly bolus topotecan and subsequent platinum retreatment outcomes in recurrent ovarian cance

Abstract

PURPOSE: The goal of this study was to evaluate the outcomes and response in a cohort of patients with presumed platinum-sensitive disease who were subsequently retreated with platinum after receiving weekly bolus topotecan at the time of initial recurrence.