Lurbinectedin Is Cost-Effective as a Second-Line Treatment in SCLC

Apar Kishor Ganti, MD

Findings from a cost-effectiveness model found lurbinectedin (Zepzelca) to be a cost-effective second-line treatment option for patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy, according to findings presented at the 2023 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) global conference.¹

The incremental cost-effectiveness ratio (ICER) of lurbinectedin vs the external control arm (ECA) was $20,691/quality-adjusted life year (QALY), which is below the commonly accepted willingness-to-pay (WTP) threshold in the United States of $100,000/QALY. These findings still held true under real-world uncertainty, according to probabilistic sensitivity analysis results.

Lung cancer is the leading cause of cancer death, and SCLC specifically comprises 13% to 15% of all lung cancer diagnoses. When left untreated, the median survival for a patient with SCLC is 2 to 4 months after diagnosis. Despite treatment, the predicted 5-year survival rate is 7% in the United States. Further, over the past 2 decades, treatments and survival rates for patients with SCLC have not changed much.

"Lurbinectedin is an alkaloid that affects RNA transcription. In addition, it can also result in the formation of DNA adducts, DNA double strand breaks and disrupts interactions between DNA and proteins. The net result is that there is increased apoptosis of cells," Apar Kishor Ganti, MD, MS, University of Nebraska Medical Center, told Targeted Oncology^TM.

Lurbinectedin, a selective inhibitor of oncogenic transcription, received accelerated approval from the FDA in June 2020 as monotherapy when given at a dose of 3.2 mg/m² intravenously (IV) every 21 days for the treatment of patients with metastatic SCLC who have had disease progression on or after platinum-based chemotherapy.

Investigators developed a cost-effectiveness model to estimate the incremental cost per QALY gained when giving lurbinectedin compared with its comparators. These comparators included a mix of SCLC treatments from an ECA analysis, including platinum rechallenge (PR), topotecan (IV [TOP-IV] and oral [TOP-oral]), irinotecan, nivolumab (Opdivo), and paclitaxel.

Findings presented at ISPOR only reported lurbinectedin vs the ECA for the overall population.

According to previous study findings looking at patients with SCLC enrolled in the basket trial (NCT02454972), lurbinectedin elicited a progression-free survival (PFS) rate of a median of 3.5 months (95% CI, 2.6-4.3) and overall survival (OS) was a median of 9.3 months (95% CI, 6.3-11.8).2 For the comparator arms, investigators estimated the hazard ratios (HR) from previously published studies that applied proportional hazard models.

Among those in the overall population, HRs were based on an ECA analysis that compared lurbinectedin with the mix of other second-line SCLC treatments. For the ECA, the median OS was 4.6 months (95% CI, 2.6-9.1).1 In the subgroup analysis for patients with platinum-sensitive disease, lurbinectedin led to significantly greater OS rates vs treatment with PR (HR, 0.42; 95% CI, 0.30-0.58), TOP-IV (HR, 0.43; 95% CI, 0.26-0.70), and TOP-oral (HR, 0.43; 95% CI, 0.27-0.67).

Investigators also assessed health-related quality-of-life estimates based on published literature, and the utility for stable disease was 0.818 and utility for progressed disease was 0.69, respectively.

The total cost consisted of second-line and subsequent treatment acquisition and administration costs, serious myelosuppression-related adverse event management, primary and secondary prophylaxis, office visits, monitoring, and mortality cost.

Regarding safety, rates of serious adverse events (SAEs) were estimated per pivotal trials of respective treatments. Only myelosuppression-related SAEs were modeled, including anemia, leukopenia, neutropenia, febrile neutropenia, and thrombocytopenia. The analysis also noted that the hospitalization rate for febrile neutropenia and other myelosuppression-related SAEs was estimated to be 95% and 10%, respectively.

Looking at the cost-effectiveness acceptability curve for the overall population, lurbinectedin remains 100% likely to be cost-effective vs ECA when starting at a WTP threshold of $45,000/QALY. Results from a deterministic sensitivity analysis indicated that the rate of primary and secondary granulocyte colony-stimulating factor (G-CSF) use are the most influential variables affecting cost-effectiveness outcomes.

For the platinum-sensitive group, the ICER for lurbinectedin was $63,017/QALY,

$53,835/QALY, and $22,999/QALY, respectively. This was well below the commonly accepted WTP threshold of $100,000/QALY to $150,000/QALY which is seen in the United States.

Higher treatment costs were also sustained with lurbinectedin vs the comparators, which were partially offset by higher primary and secondary G-CSF use and adverse events.

The patients treated with lurbinectedin had higher LYs and QALYs (1.70 and 1.15) than the patients treated with PR (0.74 and 0.52), TOP-IV (0.75 and 0.52), and TOP-oral (0.75 and 0.52). Moreover, lurbinectedin was 91%, 95%, and 100% likely to be cost-effective compared with PR, TOP-IV, and TOP-oral at a WTP threshold of $100,000/QALY, respectively.

Overall, these data show that treatment with lurbinectedin is cost-effective as a second-line treatment for patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy.

"Lurbinectedin is cost-effective when compared with other second-line options for small cell lung cancer. Even though the acquisition cost of lurbinectedin is greater, this is offset by the lower cost of managing myelosuppression, when compared with other commonly used second-line therapies. Lurbinectedin is not only safe and effective but is also cost effective in the care of patients with relapsed SCLC," added Ganti.

REFERENCES:

1. Su W, Rengarajan B, Profant D, et al. Cost-effectiveness modeling of lurbinectedin as a second-line therapy in patients with small cell lung cancer (SCLC). Presented at: 2023 International Society for Pharmacoeconomics and Outcomes Research; May 7-10. Boston, Massachusetts. Abstract EE152

2. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21(5):645-654. doi:10.1016/S1470-2045(20)30068-1