New cancer drugs are expensive but offer hope to patients, but put pressure on budgets

Linda Medendorp learned that she would die the day her son turned 18. Tests revealed that after a 51-year old woman complained of persistent swallowing problems, she had an incurable cancer. It had spread to her stomach and rectum.

She said that “it was the worst nightmare”, but “there was one positive factor in all of the bad news”. The characteristics of her tumour meant that she was eligible for a Dutch study of a checkpoint inhibitor, which removed brakes from the immune system preventing it from attacking cancerous cells. She suddenly had a small glimmer of hope.

Opdivo by Bristol Myers Squibb is an immunotherapy. It’s one of many new classes of cancer treatment that have emerged in the last few years, making the outlook more positive than ever.

Some of the other potentially revolutionary advances are highly targeted treatments, such as antibody drug-conjugates, an advanced form chemotherapy, and radioligands that combine a nuclear isotope, with an antibody, to irradiate tumor cells.

For health systems already struggling with the rising and aging population before Covid ravaged their budgets, innovation is not divorced from price. A year’s supply Opdivo, at its list cost, costs nearly $200,000 according to a calculation by health policy consultancy ATI Advisory.

Denis Lacombe is the chief executive of European Organisation for Research and Treatment of Cancer. He said, “All of these drugs are extremely expensive.”

According to IQVIA Institute for Human Data Science research, a surge in innovative drugs, as well as a global push for early diagnosis and expanded access to treatment led to soaring global oncology drug spending to $223bn. The Institute expects that the number will reach $409bn in 2028.

The mismatch between demand and resources is a problem that clinicians face every day. Lillian Siu is an oncologist and researcher at Toronto’s Princess Margaret Cancer Centre. She strives to make new advances in cancer treatment. As a doctor, she understands the frustration of not being able to provide the best treatment.

She said that just a day before, she tried unsuccessfully to get a patient access to a medication “off-label”, i.e. reimbursement for the use of the drug beyond its approved application.

It is not easy to discuss with patients that they don’t have insurance or funding for the drug you think may help them. This is especially true for rare tumors, where there are often no clinical trials or drug approvals.

The nature of some treatments makes it difficult to determine whether or not they are worth the money.

Many of the new drugs are classified as “precision medicines” – tailored treatments for tumours with specific genetic characteristics. This niche approach, however, means that the number of potential patients who qualify for treatment is “declining” according to Emile Vst, professor of medical oncology, at the Netherlands Cancer Institute.

He said that more and more trials are being conducted without a comparison group, or as “single-arm” studies. This creates “the inherent danger of overestimating the value” a medicine.

To compensate for this lack of data he created in 2016 the “drug discovery protocol”, also known as DRUP. This protocol has since been replicated in a variety of countries in Europe, and involves treating patients with advanced cancer with drugs that are not approved by the FDA, based on the genetic profile of the tumour.

In some cases, manufacturers pay for the initial four months. The healthcare insurer will pay for the continued treatment if the drug is effective.

Voest said that in the absence of enough evidence, the system bridges the gap between payers and pharmaceutical companies.

In the last eight years, more than 1,500 people have been treated with the scheme. 37 drugs were made available outside of their “label” to patients.

Medendorp is one of the beneficiaries. She felt immediate effects from her treatment and realised after just two infusions she could eat easier. “It’s incredible, because I didn’t have surgery. “The medicine was like an initial sign to my immune system that it could clean up all of the cancer,” said she.

The Netherlands has now been recognized as a leader on the international stage in demonstrating how valuable medicines are. Six countries are conducting similar trials. These include Norway, Finland, and Denmark. “We’re working together to expand this to 15 other countries in the EU including the UK,” Voest stated.

Voest has overseen a separate initiative that collects “real-world evidence” about how a drug works with a broader population of patients, who may not have met the inclusion criteria in a clinical study.

Sarah Emond is the president of the Institute for Clinical and Economic Review which measures the cost effectiveness of drugs.

She noted, however, that the Food and Drug Administration had approved many innovative treatments via an “accelerated pathway”, which relies on surrogate endpoints like tumour shrinkage instead of proof of improved life expectancy. This meant that drugs were often introduced to the market with little evidence showing they would improve survival.

She added that some manufacturers fulfilled the “social contract”, which required them to perform additional studies in order to confirm the effectiveness of their drug once it was used. “But there are also those that don’t.” . . Not doing the tests as quickly as you should”.

Arrangements based on outcomes are usually kept secret, if they even exist. Pfizer’s 2021 program, in which payment was linked to the effectiveness of Xalkori (a drug used to treat non-small lung cancer), became public knowledge. Pfizer stated that it was always intended to be a pilot program, which ended June 2022. However, they did not rule out the possibility of extending this approach in the future.

Experts say that one of the most concerning aspects of newer oncology treatment is that, despite recent breakthroughs in understanding human biology, it is not always clear if and when a particular treatment can be safely stopped or if the dose determined through clinical trials was the best.

Regulators are starting to pay attention. Lacombe is co-chairing the European Medicines Agency cancer medicine forum with Francesco Pignatti. Francesco Pignatti is the head of oncology at the agency. They are looking at clinical trials that address “patient-centred” questions, such as when to de-escalate treatment and which patients benefit more from side effects like toxicity.

Yasushi GOTO, of the National Cancer Centre, Tokyo, was faced with a dilemma when he heard about such trials. The industry may be afraid of losing revenue.

He said that all drugs in Japan which receive regulatory approval are reimbursed by law. The ageing population is putting an unsustainable strain upon the health insurance system. This has led the government to reduce the prices they are willing to pay.

Researchers like him are now looking at ways to reduce the cost of drugs by using immunotherapy in smaller doses and for shorter durations without sacrificing effectiveness.

It has been challenging to secure funding and recruit for trials that test these thes. But he believes this approach is the best balance between cost-effectiveness and breakthroughs.

“I am aware that innovation is important. . . But I think that cost and sustainability is too,” he said.

Ivana Cattaneo is the chair of the oncology platform of the European Federation of Pharmaceutical Industries and Associations. She is cautious about reducing the dosage or duration of the drug from what was used in the clinical trials, without the “same level of evidence” which led regulators in the first instance to approve the medication.

Cattaneo is also the executive director for oncology at Novartis. She believes that governments and health systems need to change their approach to calculating value. They should recognize that certain treatments are capable of delivering cures which, over time, will result in huge savings for both health systems as well as wider economies.

She said that people could return to their lives, go back to work and be productive while enjoying their families. The industry “gives back a great deal to society through innovation”, but is “trapped in an old way thinking” which only considers immediate clinical benefits.

Medendorp, who was diagnosed almost four years ago, believes that her prognosis in the Netherlands is very good. She continues to have regular tests. She is grateful for the medical advancements that saved her and volunteers on a program that encourages cancer patients to take up sport. She also prioritizes spending time with family. Recently, she went to the Paris Olympics with them.

“Suddenly, I feel alive again.”