Epidermal growth factor receptor blockers for the treatment of ovarian cancer.
Haldar K., Gaitskell K., Bryant A., Nicum S., Kehoe S., Morrison J.
BACKGROUND: Ovarian cancer is the seventh most common cause of cancer death in women world-wide. Treatment consists of a combination of surgical debulking and platinum-based chemotherapy, alone or in combination with paclitaxel. Between 55% and 75% of women who respond to first-line therapy relapse within two years of completing treatment. Second-line chemotherapy is palliative and aims to reduce symptoms and prolong survival. Increased understanding about the molecular basis of ovarian cancer has led to the development of novel agents, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, and their effectiveness and toxicities in women with advanced ovarian cancer needs to be assessed. OBJECTIVES: To compare the effectiveness and toxicities of epidermal growth factor receptor (EGFR) inhibitors alone or in combination with standard chemotherapy in the treatment of ovarian cancer. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) Issue 4, 2010, MEDLINE and EMBASE up to October 2010. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies, and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing anti-EGFR agents with or without conventional chemotherapy versus conventional chemotherapy alone or no treatment in women with histologically proven ovarian cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. We reported adjusted hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received gemcitabine plus pertuzumab and gemcitabine plus placebo. MAIN RESULTS: We found only one completed and three ongoing RCTs that met our inclusion criteria. The completed trial randomised 131 women with relapsed ovarian cancer to receive gemcitabine and pertuzumab or placebo and gemcitabine (control). There was no statistically significant difference in overall survival (OS), progression-free survival (PFS) and response between women who received gemcitabine and pertuzumab and those who received control, although PFS approached borderline significance (adjusted HR = 0.66, 95% CI 0.43 to 1.03; P = 0.06). The trial reported a higher rate of adverse events in the gemcitabine and pertuzumab arm for most outcomes, but most were not statistically significant (although many approached borderline significance) because the trial lacked statistical power due to its relatively small size and the low number of observed events. The trial was at moderate risk of bias. AUTHORS' CONCLUSIONS: EGFR inhibitors, including pertuzumab, may add activity to conventional chemotherapy for treatment of platinum-resistant ovarian cancer. Certain subsets of women with particularly aggressive tumours resistant to conventional chemotherapy may benefit from EGFR inhibitor treatment. Further RCTs are necessary before EGFR inhibitors are introduced as first- or second-line treatment of ovarian cancer.