Evolent program flags low-value regimen years ahead of failed clinical trial
September 9, 2026Long before recent trial results showed that a lung cancer treatment had no survival advantage, Evolent was following the early evidence and working with providers to avoid it.
By Andrew Hertler and Amy VanGalder
The cancer treatment landscape is shifting at a breathtaking pace, with potentially transformative new therapies in areas such as pancreatic cancer and melanoma. While we hope every new medicine will help people live much longer, better lives, only a portion will truly deliver. That’s why Evolent’s oncology team scrutinizes the evolving evidence to determine which regimens deliver superior clinical outcomes, and why we also don’t hesitate to let providers know when a treatment falls short.
The value of this work was underscored this summer. In June, Jazz Pharmaceuticals announced that its medicine Zepzelca had failed to improve survival in a clinical trial for second-line or later treatment of small cell lung cancer. Then, in August, the company said it would work with the FDA to remove this six-year-old indication from the medication label.
Yet, for more than four years, Evolent’s oncology team had already been working with providers to steer away from Zepzelca in this setting. Not only had it failed in an earlier trial to show that it was helping patients live longer than they would with other regimens, but it had a much higher price tag. At nearly $43,000 for 3 months, it was about 200 times the cost of one longstanding treatment and eight times the cost of another option.
In May 2022, we compiled the evidence into a detailed memo and sent it to the oncology practices we work with across the U.S. We followed up with a multifaceted campaign to engage oncologists and oncology pharmacists around the data, an effort which continues to this day. While it’s difficult to precisely measure the impact of these efforts, this program has helped avoid millions of dollars spent on low-value treatments that, unfortunately, were unlikely to provide a survival advantage.
One of many low-value regimens
Zepzelca for second-line or later treatment of metastatic small cell lung cancer is among 60-plus cancer therapies designated by Evolent as low-value regimens. Spanning 10 common cancer types, these regimens have no meaningful survival advantage, higher toxicity, or extremely high cost compared to clinically similar options. Low-value regimens represent about 1% of all the requests that Evolent receives in medical oncology, but they pose an outsize risk to the quality and affordability of care.
Labeling a treatment as low value is not something we take lightly. These regimens often bring fresh hope for hard-to-treat cancers. Like Zepzelca, they may be the first new medicine for an indication in many years. Yet, we need to balance hope for breakthrough therapies with a clear-eyed assessment of the data.
Making those evaluations is the job of Evolent’s board-certified oncologists and oncology pharmacists, who are constantly poring over new evidence in our rapidly evolving field. They not only make recommendations for which regimens we list as preferred in our clinical pathways, but also those that should be low value. We seek to make these judgments as consistent as possible. For example, when a treatment is approved based on early-stage evidence, we apply an Evolent-designed scoring framework called the Clinical Benefit Index to objectively score its real-world benefit.
Before adding anything to our low-value regimen list, it must be approved by Evolent’s Oncology Scientific Advisory Board, a group of leading community and academic oncologists.
Covering the gaps in our medication approval system
We created the low value regimen program because we can’t afford to wait for the FDA or pharmaceutical companies to act when it comes to underperforming oncology treatments. In our medication approval system, it is much easier to get a promising but unproven medicine into the market than it is to remove one that later turns out to be inferior.
One reason contributing to this is that FDA approval is often based upon surrogate outcome measures. Zepzelca, for example, received accelerated approval based on the percentage of patients who responded to the medicine (30-35%) and the duration of that response (5.1 months). Yet such measures do not always translate to longer survival or better quality of life. Even when oncology treatments do eventually graduate from accelerated to regular FDA approval, fewer than half do so based on improvements to overall survival.
Therapies also reach the market despite flawed trial designs. Zepzelca’s initial approval in 2020, for example, was based on a trial with a relatively healthy population. Patients whose cancer had spread to the central nervous system make up about half of all metastatic small cell lung cancer patients, but they were excluded from the earlier trials. When these patients were included in the latest trial, those receiving only Zepzelca had lower survival, as did the overall trial population.
In our medication approval system, it is much easier to get a promising but unproven medicine into the market than it is to remove one that later turns out to be inferior.
It is also not uncommon for confirmatory trials, which are required by the FDA to establish the clinical benefit of accelerated approval medicines, to take longer than they are supposed to. As our Evolent colleague Terra Wonsettler wrote in Evidence-Based Oncology, while the FDA typically requests that these trials be completed over 2 to 4 years for anticancer medicines, nearly half missed their deadline. The longer the wait, the longer patients and providers must live with greater uncertainty around the outcomes of a regimen. Meanwhile, these therapies can become more entrenched in providers’ ordering patterns.
Zepzelca’s confirmatory trials took a tumultuous path over six years. Results of an earlier trial, announced just months after accelerated approval was granted, did not establish a survival benefit. Yet, the FDA noted that the Zepzelca dose in the confirmatory trial was lower, and it allowed the medication to stay on the market so other trials could continue. Years later, we know that the results have not improved.
How Evolent discourages low-value regimens
To be clear, if an oncologist wants to order a low-value regimen for an FDA-approved indication, they can typically still do so. Our program aims to make sure they have all the evidence and consider preferred alternatives before doing so.
Aside from writing and sharing evidence reviews for these regimens, we take a multifaceted approach to engaging providers:
- Proactive quarterly meetings with oncology practices. We frequently highlight low-value regimens during our virtual and in-person discussions with oncology practices. We present evidence around these regimens, share scorecards on their use of low-value regimens, and have healthy give-and-take with oncologists and oncology pharmacists. For instance, providers have told us that they favored Zepzelca for lower rates of certain (but not all) toxicities and an easier administration schedule — valid points but not enough in our opinion to outweigh the extreme cost differential and lack of survival advantage.
- Labeling low-value regimens on our clinical pathways. Providers using our clinical decision support portal can typically get automatic approval for preferred regimens, while selecting a low-value regimen triggers outreach from an Evolent oncologist.
- Peer discussions. During outreach, Evolent’s oncologists seek to learn more about the patient’s case, share the evidence for a regimen to be listed as low-value, and discuss preferred options. Through these conversations, we hope to shape long-term ordering patterns.
- Financial incentives. In some markets, we have created a bonus pool for providers structured to align provider behavior with quality outcomes and evidence-based care. The bonus pool increases with each preferred regimen a provider orders and decreases by an even greater amount if they instead select a low-value option — reinforcing that the incentive rewards high-value treatment choices.
As we reported last year, our interventions helped us achieve a 20% reduction in the use of all low-value regimens with one national payer.
Clinical quality always comes first
Our low-value regimen program addresses the affordability crisis in oncology care. Yet, the focus remains fixed on achieving the best clinical outcomes. We don’t need to look beyond small cell lung cancer for an example. Imdelltra is a second-line treatment that received accelerated approval in May 2024 and quickly earned regular approval in November 2025, based on a 5.3-month survival advantage. While it costs twice as much as Zepzelca, it became a preferred option on Evolent’s pathways in 2024. Similarly, Zepzelca remains a preferred regimen for first-line maintenance therapy of small cell lung cancer when combined with another medication.
When treatments are clearly superior, they should be preferred. We should just avoid spending exorbitant amounts on regimens with outcomes that are no better or worse than the alternatives.
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