New hope for the platinum resistant

FDA approves pembrolizumab with paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma

https://tinyurl.com/dndxk5ea

Paclitaxel, a combination therapy of a taxane and a platinum drug for chemotherapy of ovarian cancer has been used for more than 30 years. This combination of a cytotoxic and a growth suppressant radically changed the survival for women with this disease.

Unfortunately, drug resistance to this combination especially to the platinum drug is inevitable and for some women this occurs early in the first 6 months after initial treatment, this is known as “platinum resistance”.

Platinum resistance is a grave finding and difficult to treat. Recent results from a clinical trial called KEYNOTE-B96 have shown promising response to a new combination of immunotherapy and chemo using a checkpoint inhibitor (Keytruda) together with paclitaxel with median improved overall survival of 18 months.

Previously immunotherapy with checkpoint inhibitors has not been shown to be effective for high grade serous ovarian cancer. In the context of platinum resistance there is evidence of change in the immune profile with loss of tumour suppression genetic activity and increased circulating programmed cell death protein (PD-1). It is PD-1 which is the marker of checkpoint protection of cancer cells.

Of the 643 patients in the KEYNOTE trial about 70%  were shown to be PD-1 expressers. Severe side effects meant that treatment was terminated early for 16% of those patients who received Keytruda. However, the significantly improved survival for those women in the treatment arm of the trial has prompted FDA approval of the use of Keytruda in combination with Paclitaxel for treatment of platinum resistant ovarian cancer when PD-1 expression is present.

resistant ovarian cancer when PD-1 expression is shown.