Platinum Resistance in Ovarian Cancer

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In the setting of ovarian cancer, patients are considered platinum-sensitive if they have had a response to initial therapy and sustained it at least 6 months before requiring retreatment for recurrence or progression of disease. Patients who experience ovarian cancer recurrence >6 months and ≤12 months after prior first-line platinum-based chemotherapy are classified as partially platinum-sensitive, explains James Tate Thigpen, MD.

Platinum-sensitive patients who progress are usually retreated with a carboplatin-based doublet, such as carboplatin and paclitaxel, carboplatin and gemcitabine, or carboplatin and doxorubicin, all of which have been evaluated in phase III trials. In these studies, the combination of a platinum-chemotherapy plus paclitaxel demonstrated a median progression-free survival (PFS) of 11 months and a median overall survival (OS) of 24 months. Carboplatin plus gemcitabine demonstrated a median PFS of 8.6 months and a median OS of 18 months. Carboplatin plus pegylated liposomal doxorubicin showed a median PFS of 11.3 months and a median OS of 30.7 months.

Treatment options for patients with platinum-resistant ovarian cancer still require more investigation. The AURELIA trial demonstrated that platinum-resistant patients who were treated with a single chemotherapeutic agent in combination with bevacizumab had a survival advantage over those treated with a single cytotoxic agent in the absence of bevacizumab. Median PFS with bevacizumab was 6.8 versus 3.4 months with chemotherapy alone (HR = 0.38; P <.0001). Based on findings from this trial, the FDA approved bevacizumab for patients with platinum-resistant recurrent ovarian cancer in November 2014.

Michael J. Birrer, MD, comments that delaying platinum resistance is the current focus of research. Robert A. Burger, MD, adds that there are new data evaluating DNA methyltransferase inhibitors, such as decitabine, which may partially reverse platinum resistance, although Burger comments that this area of research is moving slowly.