Clinical Care Options - OCEANS: PFS Improvement of 4 Months With the Addition of Bevacizumab to Carboplatin/Gemcitabine in Patients With Platinum-Sensitive Recurrent Ovarian Cancer ASCO 2011

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Clinical Care Options - Oncology CME - OCEANS: PFS Improvement of 4 Months With the Addition of Bevacizumab to Carboplatin/Gemcitabine in Patients With Platinum-Sensitive Recurrent Ovarian Cancer

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OCEANS: PFS Improvement of 4 Months With the Addition of Bevacizumab to Carboplatin/Gemcitabine in Patients With Platinum-Sensitive Recurrent Ovarian Cancer

Posting Date: June 15, 2011

• OCEANS: randomized, double-blind, placebo-controlled phase III trial^[1]

Summary of Key Conclusions

• Addition of bevacizumab to carboplatin/gemcitabine yielded significant benefits vs carboplatin/gemcitabine alone in patients with platinum-sensitive recurrent ovarian cancer
  • Median PFS improved by 4 months
  • Objective response improved by 21%
  • Median duration of response improved by 3 months
  • Trend toward improved OS
    • Data not yet mature
• Safety profile of bevacizumab plus carboplatin/gemcitabine consistent with previous reports
  • No new safety signals observed
  • No gastrointestinal (GI) perforations reported

Background

• Carboplatin/gemcitabine US Food and Drug Administration approved in 2006 for treatment of platinum-sensitive recurrent ovarian cancer based on improvement in PFS vs carboplatin alone in phase III clinical trial^[2]
• Bevacizumab: humanized anti-VEGF monoclonal antibody
  • Demonstrated single-agent activity in recurrent ovarian cancer^[3,4]
• Current study assessed carboplatin/gemcitabine chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer...............cont'd

Medscape: Bevacizumab Benefits Patients With Recurrent Ovarian Cancer (bevacizumab plus carboplatin and gemcitabine followed by bevacizumab)

Bevacizumab Benefits Patients With Recurrent Ovarian Cancer

Add-on bevacizumab slows progression of recurrent ovarian cancer - - ModernMedicine

Add-on bevacizumab slows progression of recurrent ovarian cancer - - ModernMedicine


(from Reuters) "....Dr. Aghajanian and colleagues note that overall survival data from the trial are not yet available; information on clinicaltrials.gov indicates a predicted study completion date of October 2013.
For now, say the researchers, "The data from OCEANS demonstrate that the addition of BV (bevacizumab) to GC (gemcitabine and carboplatin) can improve outcomes, and ongoing studies will assess whether this ability to add benefit is universal to other platinum-based combinations."
OCEANS is supported by Genentech, which markets bevacizumab as Avastin.

abstract: Phase II Study of Gemcitabine and Docetaxel in Recurrent Platinum Resistant Ovarian Cancer

Abstract

To evaluate the activity of gemcitabine and docetaxel in patients with recurrent ovarian cancer.

Methods: 
Patients with platinum-resistant disease and prior treatment with paclitaxel received treatment with docetaxel on day 1 and gemcitabine on days 1 and 8, repeated every three weeks.

Results: 
Twenty patients, with a platinum-free interval of three months, were enrolled. Overall response rate was 25%. Treatment was associated with significant myelosuppression.

Conclusions: 
In chemotherapy-resistant patients, this regimen exhibited encouraging activity. Excessive myelosuppression led to early closure. This was prevented by administering docetaxel on day 8 (instead of day 1) and prophylactic use of G-CSF. (blood products)

abstract: Feasibility of intravenous gemcitabine and an intraperitoneal platinum agent in the treatment of ovarian cancer

prior abstract - new commentary: EvidenceUpdates - Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment

Commentary:
Oncology - Gynecology - "This negative study extends the evidence base indicating that triplet chemotherapy increases toxicity without significant survival benefit in ovarian cancer patients. Further increases in survival for this group will need to come from alternate strategies."

alternate link to abstract:
Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer

Sorafenib in Combination With Gemcitabine in Recurrent Epithelial Ovarian Cancer: A Study of the Princess Margaret Hospital Phase II Consortium

Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada; †Juravinski Cancer Centre, McMaster University,Hamilton, Ontario, Canada; ‡Fox Chase Cancer Center, Philadelphia, PA; and §National Cancer Institute, Bethesda, MD.

Abstract

OBJECTIVES: Antiangiogenic strategies have demonstrated efficacy in epithelial ovarian cancer (EOC). Sorafenib is a novel multitargeted kinase inhibitor with antiangiogenic activity. Gemcitabine has known activity against EOC. A phase 1 clinical trial of this combination suggested activity in ovarian cancer with no dose-limiting toxicity. This phase 2 study was designed to examine the safety and efficacy of gemcitabine and sorafenib in patients with recurrent EOC.

CONCLUSION: This trial of gemcitabine and sorafenib in recurrent EOC did not meet its primary efficacy end point, but the combination was associated with encouraging rates of prolonged stable disease and CA-125 response.

Summary-Overcoming platinum resistance in ovarian carcinoma

Areas covered in this review:
A systematic literature review of clinical studies published between January 2005 and March 2010 was conducted using search engines, PubMed and MEDLINE with the entry keywords ‘ovarian cancer’ and ‘platinum resistance’. This search revealed 40 clinical trials (1793 patients).

Take home message:
Analysis of recent clinical trials showed that gemcitabine-based combination chemotherapy was associated with the highest antitumor effects in platinum-resistant ovarian cancer patients during the study period.

Clinical Activity of Gemcitabine Plus Pertuzumab in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer - abstract

Conclusion: Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. Low HER3 mRNA expression may predict pertuzumab clinical benefit and be a valuable prognostic marker.

Clinical Activity of Gemcitabine Plus Pertuzumab in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

Note: The response rates in this study either alone or in combination were low. The side effects appear to be understated (abstract).