Real-World Analysis Shows High Costs, Early Discontinuation With ALK Inhibitors in Lung Cancer

Real-world treatment of patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) is marked by high drug costs and relatively short treatment durations, according to a new study published in the Journal of Managed Care & Specialty Pharmacy.

Lung cancer remains the second most common cancer diagnosis in the United States and the leading cause of cancer death. Nearly 85% of cases are classified as NSCLC, and 4% to 5% of these tumors carry an ALK gene rearrangement.

People with ALK-positive NSCLC tend to respond well to targeted therapy with tyrosine kinase inhibitors (TKIs), which have largely replaced chemotherapy as standard first-line treatment. Currently, several ALK TKIs — such as Alecensa (alectinib), Ensacove (ensartinib) and Lorbrena (lorlatinib) — are recommended as preferred therapies in the National Comprehensive Cancer Network’s treatment guidelines, but real-world data comparing their costs and outcomes have been limited.

Rahul Mudumba, M.S.

“We get one chance to give a patient the right first-line therapy, and we need to nail it,” first author Rahul Mudumba, M.S., a Ph.D. candidate in health economics at the University of Southern California, told Managed Healthcare Executive in an email interview. “Patients often develop resistance, and if the first option is suboptimal, you can’t get that opportunity back. That’s why optimizing sequencing is critical, especially in ALK-positive NSCLC, where multiple therapies are recommended as first-line options in U.S. clinical guidelines.”

The new research, which was published Aug. 30, 2025, examined outcomes for 696 patients with ALK+ NSCLC treated with first-line TKIs using a claims database. Between 2016 and 2021, patients most commonly received Xalkori (crizotinib) (53%), followed by Alecensa (38%), Alunbrig (brigatinib) (3%), Zykadia (ceritinib) (4%) and Lorbrena (2%).

The analysis found that the average monthly healthcare costs per patient reached $28,216, with a 30-day supply of an ALK TKI averaging $17,766. Median overall survival was 25.5 months, and median time to treatment discontinuation was 8 months. Fewer than 1 in 4 patients (24.3%) transitioned to another ALK TKI in the second-line setting, highlighting high rates of discontinuation.

The authors reported that their findings are consistent with prior research showing monthly treatment costs of $22,000 to $30,000 but extend earlier work by capturing the full follow-up period, including disease progression and end-of-life care. By drug, estimated monthly acquisition costs were $17,142 for Alecensa, $18,490 for Alunbrig, $14,920 for Zykadia, $18,860 for Xalkori, and $18,496 for Lorbrena. The authors noted that these data reflect real-world use and dose adjustments, making them valuable inputs for cost-effectiveness analyses.

Survival outcomes in this real-world population were shorter than those reported in clinical trials. While trials such as ALEX, ALTA-1L and CROWN have not yet reached median overall survival after several years of follow-up, this study reported a median of 25.5 months. The authors stated that this aligns with other observational research and likely reflects the broader range of patients and comorbidities seen in routine care.

Relatively few go on to second-line treatment

Second-line treatment rates were lower than expected. Only about a quarter of patients received another ALK TKI after discontinuing first-line therapy, compared with 38% to 54% in clinical trial populations. According to the authors, factors such as treatment-related toxicity, access barriers or aggressive disease progression may explain the lower rates.

Mudumba and his colleagues acknowledged several limitations. Patients were identified through diagnosis codes and pharmacy claims, which may have led to misclassification. Sample sizes for certain drugs were small, restricting comparisons across groups. The study population was limited to privately insured individuals, which may reduce generalizability. Claims data also lack details on disease severity, adherence and physician rationale for treatment selection.

“Treating ALK-positive lung cancer costs about $28,000 per patient per month, and patients discontinue therapy at much higher rates than in trials and have poorer prognosis, with 1 in 4 ever reaching a second-line targeted therapy,” Mudumba said. “These gaps underscore the need for managed care to weigh not just efficacy but also durability, toxicity, and financial toxicity when making formulary decisions.”

“By supplementing trial data with real-world evidence, we can give providers, payers, and patients more certainty that they’re making the best possible choice at the most important decision point,” Mudumba added.