By: Evan Friend, MD
The concept of maintenance therapy is based on the idea that by continuing treatment, patients will delay the time to subsequent recurrence or progression of the disease. Whether or not this therapy will lead to improved long-term survival is a question that has yet to be answered and multiple clinical trials are in progress to address this.
The decision to pursue ongoing or “maintenance” therapy for a woman achieving an ovarian cancer remission is certainly not clear-cut and therefore, can be a difficult one. The majority of women with ovarian cancer are able to achieve remission after the completion of front-line chemotherapy following successful primary surgery for resection of the tumor. It is not unusual, however, for women to have mixed emotions at the time of completion of chemotherapy. On the one hand, there is a sense of relief in making it to the “finish line,” but on the other hand, a patient may feel anxious due to the fact that treatment is no longer taking place.
Thus, one may be fearful that the tumor burden is not 100% gone, or that cancer may recur without ongoing chemotherapy. This is where maintenance therapy may be appropriate. Maintenance chemotherapy can involve the continuation of one of the same agents utilized in the initial treatment, such as paclitaxel (Taxol). Given as a maintenance treatment, this chemotherapy drug is usually given less often or at a lower overall cumulative dose for a period of several months and possibly as long as one year. To date there has been no single trial which clearly demonstrates significant long-term survival benefits for maintenance Taxol, although a 2010 meta-analysis (Hess L et al Cancer 116:5251-60) that evaluated the pooled results from multiple trials suggested that women with advanced stage ovarian cancer may benefit. Results from ongoing clinical trials should address the value and appropriate dosing schedule for maintenance Taxol (e.g., GOG-212).
Drugs used as maintenance therapy can also be different from those that have induced remission or resulted in stable disease. For example, the PARP inhibitor, olaparib, and the angiogenesis inhibitor, pazopanib, have recently been tested in this setting. Increased time to disease progression was observed with each of these drugs in early trials and phase III trials will determine whether there will also be an overall survival advantage for women who take these drugs as maintenance therapies. (See our accompanying article on the PARP inhibitors). In addition to increasing overall survival, any regimen involving continuation of therapy to “maintain” the response or stable disease state also aims to maximize the patient’s overall quality-of-life for as long a time as possible, while clearly recognizing that continuation of treatment may have a negative impact. This may be related to adverse side effects, such as peripheral neuropathy and intermittent low white blood cell counts with increased susceptibility to infections as well as the time and effort required for the patient participating in an ongoing long-term therapy program involving intravenous chemotherapy.
Anticipating that the role of maintenance therapy will be ultimately proven in the setting of a randomized clinical trial, the next critical issue will be to identify the type of maintenance intervention able to prevent cancer recurrence, while avoiding toxicity and preserving quality of life. We expect that the selection of this maintenance therapy will be informed by the patient’s tumor molecular profile.