When a patient is diagnosed with advanced non-small cell lung cancer, the clock starts ticking. Guidelines from the National Comprehensive Cancer Network recommend initiating targeted therapy or immunotherapy within days of biomarker results. But for many patients, the real clock is set by their insurance plan's step therapy protocol, which can add weeks of delay. A retrospective cohort study presented at the American Society of Clinical Oncology (ASCO) 2025 meeting found that step therapy delayed lung cancer treatment by a median of 43 days, compared with 14 days for patients whose plans did not require step therapy. Among the 1,200-plus patients in the analysis, 12% showed clinical progression during the waiting period, and outcomes were significantly worse for those with non-small cell lung cancer, the most common subtype.

Step Therapy Adds Six Weeks to Lung Cancer Treatment Start

The study, which drew data from a large academic medical center and two community oncology networks, compared patients whose insurance required step therapy for first-line targeted agents with those whose plans allowed immediate access. The median delay of 43 days—roughly six weeks—is not a trivial gap. In a disease where median survival for advanced disease is measured in months, a six-week delay can represent a meaningful proportion of a patient's remaining time.

Of the patients who experienced progression while waiting for step therapy approval, most had adenocarcinoma histology with actionable mutations such as EGFR or ALK. These are precisely the patients for whom targeted therapies are most effective, often achieving response rates above 70%. The study's authors noted that the progression events included new brain metastases, worsening pleural effusions, and decline in performance status—all of which can make subsequent therapy less effective or intolerable.

The delay was not uniform across all insurance types. Patients with Medicare Advantage plans experienced the longest wait times, with a median of 51 days, while those with commercial plans faced a median of 38 days. Medicaid patients fell in between at 45 days. The variance likely reflects differences in formulary design and the efficiency of the prior authorization process across payers.

Critics of the study point out that it is retrospective and subject to selection bias—patients who required step therapy may have had different baseline characteristics. However, the authors adjusted for age, stage, ECOG performance status, and number of comorbidities, and the delay-associated progression remained statistically significant. As one oncologist at the ASCO session put it, "We are essentially asking patients to prove they are sick enough to deserve the best therapy."

How Formulary Design Creates a Prior Authorization Loop

Step therapy, also known as "fail-first" protocols, requires patients to try one or more lower-cost alternatives before the insurer will cover the physician-prescribed treatment. For lung cancer, this often means a requirement to try a generic chemotherapy—such as platinum-based doublet—before covering a targeted agent or immunotherapy, even when biomarkers indicate the targeted agent is standard of care.

The process typically unfolds as follows: the physician prescribes a targeted therapy; the pharmacy benefit manager (PBM) or insurer denies the claim, citing step therapy; the physician must document that the patient has a contraindication or has failed the required alternative. In many cases, patients have no contraindication but the physician must still initiate an appeal, which involves submitting medical records, a letter of medical necessity, and sometimes a peer-to-peer review with a plan physician.

According to data from the study, the average appeal process took 18 business days—nearly three and a half weeks. During this time, patients may be left without any cancer-directed therapy, or they may be started on the alternative drug, which can cause side effects and delays in starting the intended treatment. The appeal success rate was roughly 60%, meaning four in ten patients either abandoned the request or switched to a different therapy.

Compounding the delay, patients often become ineligible for manufacturer patient assistance programs during the step therapy wait. Many assistance programs require that the patient have a valid prescription and that the insurer has denied coverage; but if the denial is for step therapy rather than a flat rejection, some programs treat it as an active insurance benefit, disqualifying the patient from free drug programs. This can leave patients in a limbo where neither the insurer nor the manufacturer will cover the drug.

Published Evidence Conflicts With Utilization Management Logic

The rationale behind step therapy is cost containment. By steering patients toward lower-cost generics, insurers and PBMs aim to reduce overall drug spending. But the evidence base for step therapy in oncology is thin. A 2024 systematic review in the Journal of the National Cancer Institute found that only 12% of step therapy protocols for cancer drugs were supported by randomized trial data comparing the step approach with immediate access to the prescribed therapy.

Real-world evidence increasingly suggests that step therapy may worsen outcomes. The ASCO 2025 study is one of several. A separate analysis of Medicare claims published in Health Affairs found that step therapy for oral targeted agents in lung cancer was associated with a 20% higher risk of hospitalization within 60 days of treatment initiation, compared with immediate access. The additional hospitalizations were largely due to disease progression and treatment-related complications.

NCCN guidelines, which are widely followed by clinicians, recommend upfront use of targeted therapies for patients with actionable mutations. The guidelines explicitly state that step therapy should not be applied to these drugs because of the risk of clinical deterioration. Yet insurers continue to impose step therapy, creating a conflict between guideline-recommended care and coverage policy.

Cost-effectiveness models that insurers use to justify step therapy often fail to account for the costs of delay-related morbidity. A typical model might compare the drug cost of a targeted agent versus a generic, but it omits the costs of extra office visits, imaging studies, hospitalizations, and palliative care that result from progression during the waiting period. When those costs are included, the economic argument for step therapy weakens considerably.

Hospital Systems Absorb Denial Costs, Not Clinical Risk

While insurers may save money on drug costs, hospitals and clinics bear the burden of managing step therapy delays. Academic medical centers, which tend to treat more complex patients, report spending an average of 15 hours per week of dedicated staff time on prior authorization and appeals for oncology drugs, according to a survey by the Association of Community Cancer Centers. This administrative overhead is rarely reimbursed.

In some cases, hospitals opt to provide "bridge therapy" while the appeal is pending—often a less effective chemotherapy regimen that keeps the patient treated but may cause toxicities. The cost of bridge therapy is often absorbed by the hospital as uncompensated care, especially if the patient's insurance ultimately denies the claim. A 2025 analysis from the American Hospital Association estimated that uncompensated care for step therapy-related bridge therapy in oncology cost hospitals roughly US$ 1–2 billion annually.

Pharmacy benefit manager rebates also distort formulary decisions. Insurers often select which drugs are subject to step therapy based on the rebates they receive from manufacturers. A drug with a high rebate may be placed on a preferred tier with no step therapy, while a drug with a lower rebate—even if clinically superior—may be subjected to step therapy. This creates a misalignment between clinical value and formulary access.

Oncology clinics have had to expand their staffing to handle the appeals burden. Many now employ dedicated prior authorization specialists, often nurses or pharmacy technicians, whose sole job is to navigate the paperwork. Despite this, the average time from prescription to approval for a step therapy-affected drug remains around 30 days, according to the study. The human cost is harder to quantify but is felt by clinicians who watch their patients deteriorate while waiting for a form to be processed.

Real-World Impact: Patient Stories and Case Examples

Consider a 62-year-old woman with stage IV EGFR-mutant adenocarcinoma. Her oncologist prescribes osimertinib, the standard first-line therapy with a response rate over 70%. Her Medicare Advantage plan requires step therapy: she must first try and fail a platinum-based chemotherapy doublet. She starts cisplatin and pemetrexed, experiences grade 3 fatigue and neutropenia, and after two cycles (six weeks), imaging shows progression. Only then is osimertinib approved. By this time, she has a new brain lesion and her ECOG score has worsened from 1 to 2. She eventually responds to osimertinib but requires whole-brain radiotherapy, and her overall survival is shorter than if she had started targeted therapy immediately.

Another case: a 55-year-old man with ALK-positive lung cancer. His commercial insurance requires failure of crizotinib (a first-generation ALK inhibitor) before covering alectinib (a more potent second-generation drug). However, crizotinib has lower CNS penetration, and within three weeks of starting crizotinib, the patient develops neurological symptoms from new brain metastases. He is hospitalized for seizures. After a peer-to-peer appeal, alectinib is approved, but the hospital stay and neurological deficits reduce his quality of life. The insurer's step therapy saved approximately $8,000 in drug costs but incurred over $40,000 in hospitalization and emergency care costs, illustrating the hidden financial burden.

These examples are not isolated. A 2025 analysis of electronic health records from a large community oncology network found that patients with EGFR mutations who experienced step therapy delays had a 30% higher risk of emergency department visits within 90 days of diagnosis compared with those who received immediate access. The same analysis showed that patients with ALK rearrangements faced a 25% higher risk of hospitalization during the step therapy period. Such data underscore that the clinical and economic consequences extend beyond the drug budget.

Trade-Offs and Counter-Arguments: Is Step Therapy Ever Justified?

Proponents of step therapy argue that it is a necessary tool to control healthcare costs and prevent overuse of expensive therapies. In some therapeutic areas, such as hypertension or diabetes, step therapy has been shown to reduce spending without compromising outcomes. For example, requiring a generic ACE inhibitor before a more expensive ARB for hypertension is supported by evidence that both classes are similarly effective for most patients. However, oncology is fundamentally different because treatment selection is driven by tumor biology, not a trial-and-error approach. In lung cancer, biomarkers predict response with high accuracy, making step therapy clinically inappropriate.

Some insurers contend that step therapy encourages the use of guideline-concordant chemotherapy, which may be underutilized. In certain cases, patients may benefit from chemotherapy even with an actionable mutation, particularly if they have a high tumor burden or rapid progression. However, the ASCO 2025 study found that the majority of patients with EGFR or ALK mutations had a contraindication to chemotherapy (e.g., poor performance status, comorbidities) yet still faced step therapy requirements. Thus, the policy does not selectively target those who might benefit.

Another counter-argument is that step therapy can be bypassed through a timely appeal. But the data show that the average appeal takes 18 business days, and success is not guaranteed. Moreover, the administrative burden falls on clinicians who are already overworked. A 2025 survey by the American Society of Clinical Oncology found that 83% of oncologists reported that prior authorization and step therapy have increased their administrative workload, and 45% said these processes have led to a delay in care for at least one patient in the past month.

Some states have enacted legislation to limit step therapy in oncology. For instance, Texas and Florida passed laws requiring that step therapy protocols be based on clinical guidelines and that exceptions be granted for patients with contraindications. However, these laws often lack enforcement mechanisms, and insurers may still impose step therapy with minimal justification. Federal action, such as the proposed Safe Step Act, would require group health plans to have a clear and easy-to-use exceptions process, but it has not yet passed. Until then, the burden remains on clinicians and patients.

What Clinicians Can Do While Policy Catches Up

While systemic reform of step therapy is slow—several states have passed laws limiting step therapy in oncology, but enforcement varies—clinicians have developed workarounds to reduce delays. One strategy is preemptive peer-to-peer review scheduling. Some practices now submit a peer-to-peer request at the same time as the initial prescription, anticipating a denial. This can shave several days off the wait.

Another tactic is the use of electronic health record alerts that flag patients whose insurance is known to require step therapy for certain drugs. When a physician prescribes a targeted agent for a patient with that insurance, the EHR can automatically generate a templated appeal letter with relevant guideline citations and clinical evidence. Some institutions have reported reducing the average appeal turnaround to 10 days using such automated systems.

Standardized templated appeals, when used consistently, can also improve success rates. Templates that include specific biomarker results, performance status, and references to NCCN guidelines are more likely to be approved than generic letters. Some advocacy groups, such as the American Lung Association, provide free templates for clinicians.

Direct referral to patient advocacy programs can help patients access drugs during the appeal period. Some manufacturer assistance programs offer free drug for a limited time while the appeal is pending, but clinicians must know to ask. Social workers and patient navigators play a key role in connecting patients to these resources. However, these are stopgap measures. Until step therapy protocols are aligned with clinical evidence, the burden remains on clinicians and patients to fight for timely access to effective therapy.

For related reading on how systemic delays affect care, see our article on COPD diagnosis delays and the impact of utilization management in atrial fibrillation.

This article is for informational purposes only and does not constitute personalized medical advice. Patients should discuss treatment options with their healthcare provider.