Cancer Drug Combos Causing Cost-Effectiveness Headaches

Barcelona — The increasing use of drug combinations in oncology will lead to greater uncertainty over cost-effectiveness, argue leading experts, with patients potentially left unable to access combination therapies that offer improved outcomes but at inflated cost to the health service.

Carla Deakin, programme director, Commercial & Managed Access at the National Institute for Health and Care Excellence (NICE), told delegates at the European Society for Medical Oncology (ESMO) Congress 2019 that there has been an increase in the number of cancer drug combinations the UK's health watchdog has been asked to assess in recent years.

However, she said that determining their combined cost-effectiveness is not a simple task, an issue that was highlighted by Dr Kerstin Vokinger, from the University of Zurich, Switzerland, and colleagues, who found no correlation between the clinical effectiveness and price of oncology drugs across five major countries.

This issue is therefore set to have repercussions for the health service and patients alike, which was underlined when NICE caused consternation this week by rejecting an immunotherapy–chemotherapy combination for an aggressive form of breast cancer.

Value for Money

Carla Deakin explained that NICE aims to reduce variations in the availability and quality of treatments and care and "resolve uncertainty about which medicines and treatments work best and which represent value for money".

This means treatments that not only fit with current health priorities and have a good evidence base but also that offer incremental benefits to patients and improved outcomes, all at a "justifiable price".

In the 5 years between August 2014 and August 2019, NICE appraised 94 combination therapies across all therapy areas, including 50 for oncology treatments, of which 44 were approved.

With the number of oncology combination therapies increasing year on year in that period, she suggested that this trend is set to continue.

Giving a theoretical example of a cost-effectiveness analysis, she emphasised that when assessing the combination A plus B, its effectiveness is not simply a case of adding that of the individual therapies together but "it's somewhere less than that".

She said that the "backbone therapy" of the combination needs to be considered in terms of its efficacy and where it sits in relation to cost effectiveness.

Carla Deakin explained that if it is "very, very close or at the margin of the cost-effectiveness [or] willingness to pay threshold," then it will be harder to demonstrate the cost-effectiveness of the combination therapy.

Central to this is the price of the treatments, and their relationship with their cost-effectiveness.

European and US Perspective

While Carla Deakin would not talk specifics when it came to treatment costs, Dr Kerstin Vokinger presented a poster at ESMO Congress 2019 examining price and effectiveness in the USA and England, France, Germany, and Switzerland.

She and her colleagues looked at 63 cancer drugs approved by the US Food and Drug and Administration and the European Medicines Agency, of which 73% were for solid tumors and 27% for haematological malignancies.

The team found that, compared with the USA, median cancer drug prices were 53% lower in England, 66% lower in France, 53% lower in Germany, and 50% lower in Switzerland, or 52% lower across the four European countries.

When they compared monthly drug prices with the clinical effectiveness of each drug, as measured on the American Society of Clinical Oncology Value Framework and the ESMO Magnitude of Clinical Benefit Scale, there was no correlation.

In each of the countries they examined, the researchers found that there was no significant difference in the median monthly cost between drugs with a low or high clinical benefit, on either of the measures.

Dr Vokinger and colleagues therefore call for drug pricing to "be aligned with clinical value of drugs to improve access to medicines and enable limited resources to be used for treatments that offer patients better outcomes".

Moreover, Dr Vokinger told Medscape News UK that the situation will become even more complex with the use of drug combinations in oncology.

Describing it as a "very important issue", she underlined that, in their study, she and her colleagues "only looked at single drugs because I think that’s already difficult".

Dr Vokinger believes that, in the future, novel approaches will be needed to assess combination therapies.

She said: "As drugs more frequently get combined, I really believe we need a tool or way that looks at these combinations because obviously it’s not that simple from a medical perspective that you can just take the value of each drug and add them."

Latest NICE Cancer Drug Combo Decision

This issue was laid bare on Thursday, when NICE announced in draft guidance that it will not be recommending the combination of the immunotherapy atezolizumab (Tecentriq, Genentech) and nab-paclitaxel chemotherapy in the treatment of advanced triple negative breast cancer.

NICE acknowledged in a statement that the combination therapy extends progression-free survival by around 2.5 months and increases overall survival by approximately 9.5 months.

Results from IMpassion130 with this combination, showing a 20% improvement in progression-free survival over placebo that rose to 38% among PD-L1 positive patients, were initially presented at ESMO 2018 to much fanfare.

However, delegates at the American Society of Clinical Oncology (ASCO) 2019 annual meeting were told this did not lead to a significant overall survival benefit, despite the combination leading to a numerical increase in median overall survival over placebo in PD-L1 positive patients.

NICE also heard that this aggressive form of breast cancer, which disproportionately affects women of a younger age, causes a large emotional burden on the patient’s family.

However, it underlined that in the absence of trial data comparing atezolizumab plus nab-paclitaxel with standard care treatment, it "felt that the company’s analysis indirectly comparing these treatments was unreliable and lacked validity".

The list price of a 7.5-month course of atezolizumab is £39,981, and it is estimated that around 600 people in England would be eligible for the combination therapy.

No 'Plausible Potential to Be Cost-Effective'

Despite the company behind the immunotherapy offering the National Health Service "a confidential discount", NICE said that combination "does not have a plausible potential to be cost-effective and there is no clear evidence that further trial data would resolve the uncertainties associated with this appraisal".

Meindert Boysen, director of the Centre for Health Technology Evaluation at NICE, said in a statement: "I know that today’s announcement will be disappointing for people with breast cancer, and for their families and carers…We are committed to working with the company to try to resolve the issues identified by the committee."

Delyth Morgan, chief executive at the UK charity Breast Cancer Now, agreed that the announcement is "extremely disappointing", particularly as it had been available on the Early Access to Medicines Scheme.

She said: "This combination has been available in NHS clinics for 6 months, and to now deny new patients the hope of this potentially life-extending drug is simply not good enough."

Delyth Morgan added: "Metastatic triple negative breast cancer remains one of the biggest areas of unmet need in breast cancer, and life expectancy remains heartbreakingly short.

"The evidence suggests that this immunotherapy combination could offer substantial life-extension – precious time to live and make memories with loved ones, which we know is absolutely invaluable."

Study 1631PD_PR was funded by the Swiss Cancer League.

No conflicts of interest declared.

ESMO Congress 2019: Abstract 950. Presented 17 September.

ESMO Congress 2019: Abstract 1631PD_PR. Presented 29 September.

Atezolizumab with nab-paclitaxel for treating PD L1-positive, triple-negative, advanced breast cancer [ID1522] In development [GID-TA10433]. The National Institute for Health and Care Excellence (NICE).

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