Meeting highlights from the European Medicines Agency Committee for Medicinal Products for Human Use
30.06.11
Category: Scientific News
The Committee extended indication for panitumumab to the use in combination with specific chemotherapy in patients with wild-type KRAS metastatic cancer of the colon or rectum
Following re-examination of its previous negative opinion, the European Medicines Agency Committee for Medicinal Products for Human Use at its June meeting adopted a final positive opinion, recommending the extension of indication for Vectibix (panitumumab), from Amgen Europe B.V., to include the use of panitumumab in combination with specific chemotherapy in patients with wild-type KRAS metastatic cancer of the colon or rectum (mCRC).
On 17 March 2011, the CHMP had originally adopted a negative opinion on the proposed use of Vectibix in combination with chemotherapy in patients with mCRC. At the request of the applicant, the CHMP started a re-examination of its opinion. Following the re-examination, the CHMP adopted a final positive opinion on 23 June 2011 recommending a change to the marketing authorization to add a new indication for panitumumab use in combination with specific chemotherapy treatments.
In addition to already approved indications, Vectibix from now on is approved in combination with specific chemotherapy in first and second line treatments for mCRC. In first-line positive opinion on the change to the marketing authorization is issued for combination with FOLFOX chemotherapy and in second-line treatment in combination with FOLFIRI in patients who have already received fluoropyrimidine-based chemotherapy (excluding irinotecan).
Panitumumab is a monoclonal antibody designed to attach to EGFR and it does not seem to work in tumor cells that contain mutated KRAS gene. As a support to the application, the company presented data from two main studies involving a total of 2,369 patients with mCRC. In the first study, Vectibix in combination with FOLFOX chemotherapy was compared with chemotherapy alone in patients who had not been treated before for their metastatic disease. The main measure of effectiveness was progression-free survival. The second study compared Vectibix in combination with FOLFIRI with chemotherapy alone in patients who had been treated before. The main measures of effectiveness were progression-free survival and overall survival.
At the time of the initial opinion, the CHMP was concerned about the clinical relevance of the relatively small increase in progression-free survival and the lack of improvement in overall survival seen in the studies with Vectibix in combination with chemotherapy. The Committee was also concerned about the toxicity of the combination treatment and about the risk of patients with the mutated KRAS gene being treated with Vectibix if they were not identified through appropriate tests. Therefore, at that time the CHMP was of the opinion that the benefits of Vectibix in combination with chemotherapy did not outweigh its risks. Hence, the CHMP recommended that the change to the marketing authorization should be refused.
During the re-examination the Committee looked again at the data from the main studies. A key element of the re-examination was an investigation into whether certain patients were more likely to benefit from Vectibix in combination with chemotherapy. Following advice from the experts in cancer treatment and discussions within the Committee, the CHMP concluded that although the benefits were relatively small, Vectibix in combination with chemotherapy could benefit certain patients and the toxicity could be monitored and managed appropriately, based on experience of using this type of combination treatment in clinical practice. The Committee decided that prescribers were best placed to judge this based on individual characteristics (such as overall health status, other medical problems and age) and that warnings should be included in the product information regarding the risks particularly for patients who are less likely to benefit and more likely to be harmed by the combination treatment.
The Committee also considered further information regarding tests to identify the mutated KRAS gene. The CHMP was satisfied that the tests are effective and would be carried out. It agreed that a new contraindication in patients with the mutated KRAS gene should be included in the product information to ensure the medicine is not used with FOLFOX chemotherapy in these patients.
Therefore, the CHMP concluded that the benefits of Vectibix outweigh its risks in the treatment of wild-type KRAS mCRC in combination with specific chemotherapy in first and second line treatment. The Committee recommended that the change to the marketing authorization for Vectibix should be granted.
On 17 March 2011, the CHMP had originally adopted a negative opinion on the proposed use of Vectibix in combination with chemotherapy in patients with mCRC. At the request of the applicant, the CHMP started a re-examination of its opinion. Following the re-examination, the CHMP adopted a final positive opinion on 23 June 2011 recommending a change to the marketing authorization to add a new indication for panitumumab use in combination with specific chemotherapy treatments.
In addition to already approved indications, Vectibix from now on is approved in combination with specific chemotherapy in first and second line treatments for mCRC. In first-line positive opinion on the change to the marketing authorization is issued for combination with FOLFOX chemotherapy and in second-line treatment in combination with FOLFIRI in patients who have already received fluoropyrimidine-based chemotherapy (excluding irinotecan).
Panitumumab is a monoclonal antibody designed to attach to EGFR and it does not seem to work in tumor cells that contain mutated KRAS gene. As a support to the application, the company presented data from two main studies involving a total of 2,369 patients with mCRC. In the first study, Vectibix in combination with FOLFOX chemotherapy was compared with chemotherapy alone in patients who had not been treated before for their metastatic disease. The main measure of effectiveness was progression-free survival. The second study compared Vectibix in combination with FOLFIRI with chemotherapy alone in patients who had been treated before. The main measures of effectiveness were progression-free survival and overall survival.
At the time of the initial opinion, the CHMP was concerned about the clinical relevance of the relatively small increase in progression-free survival and the lack of improvement in overall survival seen in the studies with Vectibix in combination with chemotherapy. The Committee was also concerned about the toxicity of the combination treatment and about the risk of patients with the mutated KRAS gene being treated with Vectibix if they were not identified through appropriate tests. Therefore, at that time the CHMP was of the opinion that the benefits of Vectibix in combination with chemotherapy did not outweigh its risks. Hence, the CHMP recommended that the change to the marketing authorization should be refused.
During the re-examination the Committee looked again at the data from the main studies. A key element of the re-examination was an investigation into whether certain patients were more likely to benefit from Vectibix in combination with chemotherapy. Following advice from the experts in cancer treatment and discussions within the Committee, the CHMP concluded that although the benefits were relatively small, Vectibix in combination with chemotherapy could benefit certain patients and the toxicity could be monitored and managed appropriately, based on experience of using this type of combination treatment in clinical practice. The Committee decided that prescribers were best placed to judge this based on individual characteristics (such as overall health status, other medical problems and age) and that warnings should be included in the product information regarding the risks particularly for patients who are less likely to benefit and more likely to be harmed by the combination treatment.
The Committee also considered further information regarding tests to identify the mutated KRAS gene. The CHMP was satisfied that the tests are effective and would be carried out. It agreed that a new contraindication in patients with the mutated KRAS gene should be included in the product information to ensure the medicine is not used with FOLFOX chemotherapy in these patients.
Therefore, the CHMP concluded that the benefits of Vectibix outweigh its risks in the treatment of wild-type KRAS mCRC in combination with specific chemotherapy in first and second line treatment. The Committee recommended that the change to the marketing authorization for Vectibix should be granted.
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