Exploring the Financial Advantages of Adding a CDK 4/6 Inhibitor to ER-Positive Breast Cancer

Money and stethoscope; expensive healthcare, cost of medical service - Generated with Adobe Firefly AI

During the American Society of Clinical Oncology (ASCO) Annual Meeting, Asal Pilehvari, PhD, et al¹ looked at the financial benefit of adding a CDK4/6 inhibitor to hormone therapy in women with metastatic estrogen receptor (ER)-positive breast cancer treated in the community setting.¹ Using average monthly drug and nondrug costs, the CDK4/6 arm had costs of $12,524 and $2278, respectively, vs $322 and $4265 in the hormone-only arm. Investigators concluded that it was financially beneficial for a 3.2-month progression-free survival (PFS). I will discuss some of my concerns with this study, starting with what incremental cost-effectiveness ratio (ICER) is and how it is calculated.

ICER and quality-adjusted life-year (QALY) are used to calculate the value of a particular intervention.^2-4 ICER tends to be a little more straightforward, with the difference in cost between 2 therapies divided by the difference in benefit, usually measured in years. QALY can often bring in other costs, including more subjective metrics such as quality of life. As for which benefit to use, the most common and easiest is overall survival (OS) because it is binary. Many governmental entities, such as the National Institute for Health and Care Excellence in the United Kingdom, rely on ICER to determine whether to cover the drug with public funds.⁴ Typically, most groups who use ICER recommend a maximum willingness-to-pay threshold that can range from $50,000 to $150,000 for every year of life gained. To accurately determine the ICER, the cost of the therapy, how long on average it was taken, and the OS benefit are needed. In analyzing the abstract, I used the published data from the MONALEESA-3 (M-3; NCT02422615) trial of fulvestrant (Faslodex) vs fulvestrant plus ribociclib (Kisqali) to calculate and compare ICERs.⁵

I'm choosing this study for several reasons, but the most important is reported OS benefit. In the ASCO abstract findings, the monthly cost for hormone therapy alone was $322, but with generic aromatase inhibitors costing $20, the closest drug at that price during the study period was fulvestrant. The 3.2-month PFS improvement is much lower than in findings from first-line studies using a CDK4/6 inhibitor, where it is for a year or more. Within the M-3 study findings, there were patients who received this therapy after first-line hormone therapy alone who had a 5.5-month PFS. M-3 study findings showed the PFS for fulvestrant was 9.1 months and 14.6 months for the combination, with an OS improvement of 7.7 months or 0.64 years. If we use the monthly drug cost from the abstract on the M-3 study data, the combination arm costs an extra $179,920, giving an ICER of $281,125 for each extra year of life. Adding in the respective monthly nondrug costs, the ICER is $272,472, or approximately $22,700 per month. Compared with a published article evaluating QALY from MONALEESA-7 (NCT02278120) findings, I'm not far off.⁶

Although the abstract doesn't state overall PFS or OS, there is a hint. The investigators mentioned that the total drug cost in the combination arm was $195,487, and at $12,524 per month, the PFS comes out to 15.6 months vs 12.4 months in the hormone arm. When combining the drug and nondrug costs, this comes out to $554,970, or $46,248 per month. The authors claim that adding a CDK4/6 inhibitor is cost-effective, using a willingness-to-pay threshold of $65,000 or $780,000 per extra year of PFS. There is no mention where they got this range, and it is much higher than what most have published as reasonable. To equal the ICER determined in M-3 study findings, they would have to have seen a 6.6-month improvement in PFS. I commend the authors for looking at real, community-based data to see whether using CDK4/6 inhibitors is cost-effective, but there are too many holes in the data to accurately derive a solid conclusion and the results are far above a reasonable threshold. Many patients taking these drugs require dose modifications due to toxicity, but these often don't interfere with efficacy.⁷ I chose the M-3 study because of the way the manufacturer has priced and dosed ribociclib, where dose reductions will lead to lower costs. If lowering the dose cuts the drug cost in the M-3 study by 25%, the ICER is $188,000 and is getting very close to the $150,000 upper threshold. Because dose reductions in findings from studies referred to in the package insert range from 32% to 45%, this may be a conservative assumption.^8,9 It is also why we, as treating physicians, need to encourage manufacturers to both determine what the minimum effective dose is and price their drugs where lower doses or fewer pills cost less.

Leslie Busby, MD, is chair of the US Oncology Pharmacy & Therapeutics Committee, and a medical oncologist and hematologist at Rocky Mountain Cancer Centers, Boulder, Colorado.

REFERENCES:

1. Pilehvari A, You W, Kimmick G, Bonilla G, Anderson R. Unveiling the cost-effectiveness of CDK4/6 inhibitors in treating patients with HR+/HER2- metastatic breast cancer: A closer look at nonmedication expenses. J Clin Oncol. 2024; 42(suppl 16; abstr 1532). doi: 10.1200/JCO.2024.42.16_suppl.1532

2. Institute for clinical and economic review. Value Assessment Framework. Updated September 25, 2023. Accessed July 10, 2024. https://tinyurl.com/5c8a2uc3

3. Sanders GD, Neumann PJ, Basu A, et al. Recommendations for Conduct, Methodological Practices, and Reporting of Cost-effectiveness Analyses: Second Panel on Cost-Effectiveness in Health and Medicine. JAMA. 2016;316(10):1093-1103. doi:10.1001/jama.2016.12195

4. Claxton K, Martin S, Soares M, et al. Methods for the estimation of the National Institute for Health and Care Excellence cost-effectiveness threshold. Health Technol Assess. 2015;19(14):1-vi. doi:10.3310/hta19140

5. Burke J. Should Progression-Free Survival Be the Primary End Point for Registration of Oncology Drugs? Targeted Therapies in Oncology. 2024.13(1):6. https://tinyurl.com/rbhred5z

6. Slamon DJ, Neven P, Chia S, et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2020;382(6):514-524. doi:10.1056/NEJMoa1911149

7. Jeong E, Wang C, Wilson L, Zhong L. Cost-Effectiveness of Adding Ribociclib to Endocrine Therapy for Patients With HR-Positive, HER2-Negative Advanced Breast Cancer Among Premenopausal or Perimenopausal Women. Front Oncol. 2021;11:658054. Published 2021 May 7. doi:10.3389/fonc.2021.658054

8. Ismail RK, van Breeschoten J, Wouters MWJM, et al. Palbociclib dose reductions and the effect on clinical outcomes in patients with advanced breast cancer. Breast. 2021;60:263-271. doi:10.1016/j.breast.2021.11.013

9. Kisqali. Prescribing information. https://tinyurl.com/yckbz7we