Trastuzumab-emtansine (Kadcyla®) in adjuvant treatment of adult patients with HER-2 positive breast cancer in an early stage

Zorginstituut Nederland has completed its assessment whether trastuzumab-emtansine (Kadcyla®) can be included in the insured package. The treatment is indicated as adjuvant treatment of adult patients with HER2-positive breast cancer in an early stage, who have invasive residual disease after a taxane-based and HER2-focused neoadjuvant treatment. Due to its expected high costs the Minister of Medical Care and Sports has placed the treatment in the so-called ‘package lock’ or ‘sluice’ for expensive drugs. These products can only be accepted into the insured package after the Zorginstituut has advised on their inclusion in the insured package and, where applicable, subject to Ministry negotiations to arrive at a financial arrangement with the supplier.

Zorginstituut Nederland has concluded that, in the above indication, trastuzumab-emtansine (Kadcyla®) meets the legal criterion ‘current level of knowledge and practice’. This is an effective medicinal product, but there are arguments to advise the Minister to negotiate the price of the treatment. The Zorginstituut advises the Minister to include trastuzumab-emtansine in the basic insured package only after successful price negotiations to achieve a socially acceptable price.

Criteria for including treatments in the insured package

The Zorginstituut assessed trastuzumab-emtansine based on the four package criteria:

  • effectiveness;
  • cost-effectiveness;
  • necessity;
  • feasibility.

Assessing from the perspective of the basic package which is paid from collective premiums, the Zorginstituut looks at whether new care is better than what is currently available. In doing this we look not only at the degree of certainty that has been achieved, from a scientific perspective and from the perspective of societal support, but also at efficiency aspects. The Zorginstituut was advised by two independent committees:

  • the Scientific Advisory Board (WAR) which examines data on established medical science and medical practice and determines the cost-effectiveness;
  • the Insured Package Advisory Committee (ACP) which considers the societal assessment. Stakeholders are also consulted during the process.

Integral package criteria weighting

  • In a randomised study trastuzumab-emtansine was compared with trastuzumab, which is the current standard treatment. This treatment effect is statistically significant and also clinically relevant. It is however too early to use these data to make any statement about the effect of trastuzumab-emtansine on overall survival.
  • The immaturity of the data is sufficient reason for the Oncological Medicines Assessment Committee (BOM) to deem its positive recommendation about trastuzumab-emtansine to be provisional at this stage. The EMA has required the marketing authorisation holder to provide additional data on overall survival by 2024 at the latest. The BOM committee will also assess the mature survival data and, if necessary, amend its advice.
  • The quality of life was specifically lower during treatment with trastuzumab-emtansine. This corresponds to the higher toxicity profile of trastuzumab-emtansine compared to the standard treatment trastuzumab. However, most of the undesirable effects were mild and transient.
  • Trastuzumab-emtansine is already being used in later stages for the treatment of the indication being discussed here. The use of trastuzumab-emtansine at an earlier stage of treatment for this indication therefore leads to a shift in the costs. In the future, savings may be made by preventing disease progression, but at the present time this is difficult to estimate.
  • Health care insurers have indicated to the Zorginstituut that they have negotiated very high discounts for trastuzumab and trastuzumab biosimilars. These discounts are not public. That is why the Zorginstituut has not been able to take this into account in the determination of the budget impact and the cost-effectiveness. The Zorginstituut realises that the additional costs and cost-effectiveness can be higher and less favourable than estimated, respectively.

Zorginstituut's advice

Like the BOM committee, the Zorginstituut sees trastuzumab-emtansine as a medicinal product with potential for the mentioned indication. The Zorginstituut will review its advice when the data on overall survival become available if the provisional positive advice of the BOM committee becomes a negative advice.

Bearing in mind that the additional costs and cost-effectiveness are in fact less favourable than estimated, the Zorginstituut advises the Minister to include trastuzumab-emtansine in the basic insured package only after successful price negotiations to achieve a socially acceptable price.

Appropriateness

Prior to the start of trastuzumab-emtansine for the indication mentioned above, patients must be identified as HER2-positive and having invasive residual disease following a taxane-based and HER2-focused neoadjuvant treatment. The maximum duration of treatment is 14 cycles. In case of recurrent disease or in case of non-treatable toxicity, treatment should be discontinued. The Zorginstituut is confident that the occupational group will use trastuzumab-emtansine effectively.

If trastuzumab-emtansine is admitted to the health insurance package, the Zorginstituut will actively monitor the use of trastuzumab-emtansine. We will inform the Minister about our findings no later than 2024.

This report is a summary of recommendations by Zorginstituut Nederland. The original text of this excerpt is in Dutch.