Withdrawal of Application for EMA Change to the Marketing Authorisation of Pazopanib
Extended use was intended for maintenance treatment in patients with ovarian, fallopian tube or primary peritoneal cancer
On 27 March, GlaxoSmithKline Research & Development officially notified the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application to extend the use of pazopanib (Votrient) to include maintenance treatment in women with ovarian, fallopian tube or primary peritoneal cancer whose disease improved or remained stable after first-line chemotherapy.
Votrient is a cancer medicine that contains the active substance pazopanib. It has been authorised since June 2010 for treating advanced renal-cell carcinoma and certain forms of soft-tissue sarcoma.
What was pazopanib expected to be used for?
Pazopanib was also expected to be used as maintenance treatment in women with cancer of the ovaries, fallopian tube or the peritoneum whose disease had improved or remained stable after first-line chemotherapy. It was to be used in women with cancer of stage II to IV according to the International Federation of Gynecology and Obstetrics classification.
How is pazopanib expected to work?
In ovarian, fallopian tube and peritoneal cancer, pazopanib is expected to work in the same way as it does in its existing indications.
The active substance in Votrient, pazopanib, is a protein-kinase inhibitor, meaning that it blocks some specific enzymes known as protein kinases. These enzymes can be found in some receptors on the surface of cells that are involved in the growth and spread of cancer cells, such as VEGFR, PDGFR and KIT. By blocking these enzymes, pazopanib can reduce the growth and spread of cancer.
What did the company present to support its application?
The applicant presented data from one main study involving 940 women with ovarian, fallopian tube or peritoneal cancer whose disease had not worsened after first-line chemotherapy. Patients in the study received either pazopanib or placebo for 2 years. The main measure of effectiveness was progression-free survival.
How far into the evaluation was the application when it was withdrawn?
The application was withdrawn after the CHMP had evaluated the initial documentation provided by the company and formulated a list of questions to be answered. The company had not yet responded to the questions at the time of the withdrawal.
What was the recommendation of the CHMP at that time?
At the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that pazopanib could not be approved for use in women with ovarian, fallopian tube and peritoneal cancer.
The CHMP considered that the women included in the main study were not representative of the women for whom the treatment is intended. The average age of women included in the main study was 56 years whereas the average patient is over 60 years of age at the time of diagnosis.
In addition, the CHMP was concerned that the study showed a lack of effectiveness in the subgroup of patients older than 65 years who had more advanced disease. Patients in this subgroup were also more likely to suffer serious side effects and to discontinue treatment.
There was also a high rate of treatment discontinuation and interruptions in the overall population due to side effects such as high blood pressure and low levels of white blood cells.
Therefore, at the time of the withdrawal, the CHMP was of the opinion that the benefits of pazopanib in the treatment of women with ovarian, fallopian tube and peritoneal cancer did not outweigh its risks.
What were the reasons given by the company for withdrawing the application?
In its letter notifying the Agency of the withdrawal of application, the company stated that it withdrew the application because it did not believe that the additional data requested by CHMP would allow the Committee to conclude on a positive benefit-risk balance in the new indication.
What consequences does this withdrawal have for patients in clinical trials or compassionate use programmes?
The company informed the CHMP that at the time of the withdrawal there were no patients receiving pazopanib for the first-line maintenance treatment of ovarian cancer. There are no consequences for patients in other clinical trials or in compassionate use programmes.
What is happening with pazopanib for the treatment of advanced renal-cell carcinoma and soft-tissue sarcoma?
There are no consequences on the use of pazopanib in its authorised indications.
The full European Public Assessment Report for pazopanib can be found on the Agency’s website.