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Paving the way for reimbursement of cancer combination therapies


Paving the way for reimbursement of cancer combination therapies

With the ground-breaking approval last month of the life-extending drug combination, palbociclib (a blockbuster monotherapy) with fulvestrant, for patients with advanced breast cancer,[1] as well as other recent combination therapy approvals, there is further evidence of NICE accelerating the opportunity for cancer combination therapies on the NHS.

An exponential rise in cancer treatments extending patient survival and quality of life, may now offer even more promise with the step-change in administering treatments in combination. One of the newest challenges for NICE is therefore determining whether there is sufficient added value from these combination therapies compared to current monotherapies, to warrant the higher price-tag these therapies currently dictate.


What are combination therapies for cancer?

Cancers can result from the accumulation of multiple genetic alterations and can form drug resistance to cancer monotherapies. Combination regimens for oncology (involving two or more treatments into a single regimen) have provided a solution to these challenges and have successfully established themselves as a centrepiece of cancer treatment.

In the past, regimens combined newer on-patent therapies with cheaper, off-patent medicines. However, it is becoming increasingly common for two or more on-patent medicines to be combined as part of a larger drug development pipeline.[2] This presents greater challenges to health technology assessment (HTA) bodies aiming to establish cost-effectiveness, without putting at risk the goal of early patient access to novel treatment.


The shift towards combination regimens

The fight against cancer continues to strengthen, reflected by the steep growth in new scientific discoveries and step-wise improvement in clinical efficacy each year. From 2017 to 2021, 21 novel active substances for oncology were launched globally every year, compared to only 11 per year in 2012 to 2016.[3] It is also reflected in some notable successes. Recently, promising clinical results demonstrated a 100% remission in all 12 rectal cancer patients treated with dostarlimab,[4] the first time a cancer monotherapy has achieved this feat. The continuous increase in the discovery of novel monotherapies, represents an exciting window of opportunity in the long-term, to combine effective monotherapies into combination regimens.

The growing number of active UK clinical trials investigating combination regimens for cancer, currently over 340,[5]indicates that this trend is likely to continue, as our understanding of the clinical efficacy of these treatments also improves.


The challenge

Whilst combination regimens demonstrate an exciting opportunity for patients and the oncology community, many issues around their affordability, pricing and reimbursement still stand. From the 88 completed submissions for oncology combination regimens made to the National Institute for Health and Care Excellence (NICE) since 2016, over a quarter were either not recommended or withdrawn.[6] Low success rates are not unique to NICE and can be explained using the hypothetical scenario below:[7]

Consider two individual monotherapies, each bringing a hypothetical value of ‘1’ to the patient, with both therapies also being priced the same, at a value of ‘1’. When combining the two clinically effective monotherapies into a combination regimen, the two drugs together provide a value of 1.5 (as the value of a combination therapy will never totally reach the value sum of its constituents), at a cost of 2 (1+1). Therefore, in the eyes of the payor, whilst the combination therapy brings greater value to the patient, it does not represent good value for money.

As monotherapies going through a single technology appraisal (STA) are already priced at the boundary of what an HTA agency is willing to recommend, little headroom remains for any additional costs incurred by an additional therapy, in some cases, even if the additional medicine is offered to the NHS for free.


Ensuring a triple win for pharma, payors, and patients

There is demand for pricing and reimbursement systems to look at how to improve their value assessment of combination therapies. Whilst many suggestions have been made in recent reports, [7],[8] we outline three potential solutions:

  1. Increasing the value of a combination therapy through improved clinical development: Drug developers should aim to identify suitable treatment paradigms, including duration of treatment and stopping rules, that reap maximum health benefits whilst minimising adverse effects and unnecessary treatment costs. To enforce this, HTA bodies and regulators should provide joined-up advice to manufacturers, outlining a suitable framework for trial design and data collection. Whilst it is essential to adapt R&D to suit combination therapies, meaningful progress in this space is unlikely to occur in the short-term.[9]
  2. Adjusting the price of each constituent therapy in the combination regimen: Given that the total value of a combination therapy is unlikely ever to equal the sum of the value of its constituent therapies, further work would be welcome to identify how to adjust the price the NHS pays for each component, reflecting its true value in the combination.[9] However, this is a challenge to the principle that the NHS pays the same price for a drug no matter the indication it is being prescribed for.
  3. Re-visiting the price of the backbone monotherapy: If the reimbursement of a combination therapy is being held back by a high-cost backbone monotherapy, it may be required to revisit the pricing of this existing therapy.[10] However, where the constituent therapies are offered by different owners, legal barriers exist to revisiting price and negotiation between owners are restricted by competition law. Only negotiations between the payor and each individual owner are permitted. To address this, competition law could be amended, potentially in the form of introducing a new clause to enable cancer therapies to enter re-negotiation of price should the possibility of a combination therapy be made available in its product lifetime.

Many of these changes will require cooperation and collaboration between payors, drug developers and policymakers, to ensure that reimbursement frameworks in the UK reflect innovation in combination therapy treatment. As research and investment increases, raising the stakes in this space, payors and HTA bodies can help to engage stakeholders around a potential new reimbursement model.

Early engagement will ensure a triple win for the industry; improving the clinical efficacy of therapies, streamlining payor negotiations and enabling cancer patients to benefit from early and effective access to combination therapies.


For further insight on the oncology market, please contact us at for a no-obligation, confidential conversation.

By Humoon Afsardeir
















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