Poland's AOTM Issues Recommendations for Three Oncology Drugs in Treatment of mCRC

Poland's Agency for Health Technology Assessment (AOTM) has recently issued recommendations relating to three high-cost oncology medicines in the treatment of metastatic colorectal cancer (mCRC). It has recommended that Avastin (bevacizumab; Roche, Switzerland) should not be included in the list of guaranteed treatments for insured citizens in the second-line treatment of mCRC, while it has issued a strong recommendation for Erbitux (cetuximab; Merck KGaA, Germany) in third-line treatment and a conditional recommendation for Vectibix (panitumumab; Amgen, United States).

Avastin Not Recommended

The AOTM recommends that Roche oncology blockbuster Avastin should not be included on the list of guaranteed treatments for insured citizens in the second-line treatment of mCRC, as part of a therapeutic programme. The consultative council of the AOTM reported that the drug had little clinical benefit in this indication, in combination with chemotherapy, while the risk of serious unwanted side-effects of the drug was also used to explain its position. Another factor mentioned is the high cost to the payor, the National Health Fund (NFZ). The council also points to the results of a meta-analysis published this year showing that the addition of Avastin to chemotherapy in patients with advanced solid tumours increased the risk of death. The full position paper, in Polish, is available here.

Erbitux Highly Recommended

In contrast Merck KGaA's Erbitux is highly recommended, and is put forward for inclusion in a new therapeutic programme as a third-line treatment for mCRC, rather than its present mode of financing, as a substance in the catalogue of active substances used in chemotherapy. In its position paper, the AOTM states that Erbitux "substantially extends overall survival time" and also has positive effects on the quality of life of patients without mutations of the KRAS gene (also known as "wild type"). The AOTM also states that although Erbitux is more expensive than Vectibix, its clinical superiority and its benefits for patients' quality of life mean that comparisons based on cost are not relevant in this case. The AOTM specifies that transferring Erbitux to a therapeutic programme would make it possible to ensure the best clinical effects of the drug, and also a reduction in costs to the NFZ. The full position paper, in Polish, can be accessed here.

Vectibix Conditionally Recommended

Meanwhile, the AOTM also recommends the inclusion of Vectibix as a third-line treatment for mCRC, in monotherapy, in patients with advanced form of the disease, following previous unsuccessful treatment with chemotherapy agents fluoropyrimidine, irinotecan and oxaliplatin. This recommendation is made conditionally, and is subject to the conditions of the recommendation being fulfilled; it is also only valid for three years. The decision to recommend the drug in this indication was taken despite the negative opinion of all but one of the members of the AOTM's consultative council, following which the president of the agency issued this conditional recommendation. The conditions for financing the reimbursement of Vectibix in this indication are related to indentifying the basis of determining the KRAS gene mutation, the means of funding tests to identify whether patients have the gene and identifying the centres with the competence to carry out the tests. In the recommendation paper, the AOTM's president suggests that Vectibix could even be considered to be more safe than Erbitux, and also that patient comfort when using Vectibix is greater, because it is only administered once every two weeks. Another factor in Vectibix's favour, the AOTM reports, is that the European Medicines Agency extended its registered indications to include use together with traditional chemotherapy. The restriction of the recommendation for Vectibix to three years is explained as being due to the fast pace of change and innovation in this particular area of oncology, as well as the possibility of further negotiations on price, with the possibility of a risk-sharing agreement being concluded in the future. The full recommendation can be found, in Polish, here.

Outlook and Implications

The recommendations for these three drugs in this indication come as a new therapeutic programme for the treatment of mCRC is expected to be revealed in the near future (see Poland: 12 August 2011: Long-Awaited Colorectal Cancer Therapeutic Programme to Be Finalised by AOTM in August). Previously, it had been expected that Avastin would be the second-line treatment, although ultimately it has not been recommended. The Polish Ministry of Health (MoH) could overrule this recommendation, but it is very unlikely that it will. This is a blow to Roche, although it is hardly a surprise, considering the fact that United Kingdom cost-effectiveness agency the National Institute for Health and Clinical Excellence (NICE) also failed to recommend it, and the AOTM often echoes NICE's recommendations.

In the case of Erbitux, the AOTM gives a glowing recommendation for the drug, but ironically, its inclusion on a therapeutic programme is likely to reduce its use in Poland, as it will be subject to much stricter criteria for eligibility. Vectibix and Erbitux will be subject to the same checks to identify whether patients have the KRAS gene mutation, although no three-year limit on the recommendation of Erbitux is specified. An explanation for this may be the opposition of the majority of the consultative council to the recommendation of Vectibix.

In general, the creation of a therapeutic programme is associated with quite limiting criteria for inclusion, but this should be balanced by the strong focus of the MoH on improving oncology outcomes in Poland. This is demonstrated by the recent announcement of an extra 2 billion zloty (USD699.6 million) for hospital-drug spending in 2012, compared with 2011.