A Payer’s Perspective on CDK4/6 Inhibitors

Kenneth L. Schaecher, MD, FACP, CPC
Associate Chief Medical Officer, University of Utah Health Plans,
Attending Physician - Internal Medicine, Granger Medical Clinic, Salt Lake City, UT

As pointed out in this monograph, breast cancer remains a significant issue for patients and payers, as it is one of the highest-prevalence cancers and, thus, results in high costs. A Milliman Research Report authored by Dieguez and colleagues in April 2017 found that breast cancer costs postdiagnosis averaged more than $7000 for the first several months after diagnosis, with a gradual reduction to just under $2000 per month after approximately 15 months.1 Of these costs, chemotherapy or drug therapy accounted for approximately 20%. These figures were derived from a period between 2010 and 2014, which is before the entry of newer agents such as pertuzumab or the poly (ADP-ribose) polymerase inhibitors. Thus, costs have likely risen further.

Providing coverage for the most effective agents helps patients/members reduce their costs of care at a time when they have seen a greater portion of the costs shift to them. More effective or better-tolerated agents can reduce their cost of care through reduced utilization of other healthcare resources, such as emergency department visits or inpatient hospitalization. These costs have accounted for as much as 25% of costs incurred by patients in the months following a cancer diagnosis.1

Moreover, the humanistic costs that patients/members experience when less effective or more poorly tolerated drugs are used cannot be understated.

Breast cancer is not simply one disease, and the use of more effective therapies that target different tumor markers, such as the cyclin-dependent kinase (CDK)4/6 pathway in estrogen receptor–positive breast cancer, may actually reduce the total cost of care for patients/members and payers. Published studies for palbociclib, ribociclib, and abemaciclib with or without fulvestrant or letrozole have demonstrated very favorable responses and side-effect profiles, making these drugs very reasonable choices in appropriately selected patients.

From a payer’s perspective, having 3 agents with similar mechanisms of action allows for the potential for preferred contracting, although this has been shown to be problematic in the oncology space, particularly where there is a dearth of head-to-head studies.

Data from the MONARCH 3 trial showed that adding abemaciclib to treatment with a nonsteroidal aromatase inhibitor led to a nearly 60% response rate in patients with measurable disease versus 44% for those treated with an aromatase inhibitor alone.2 Median progression-free survival was not reached in the abemaciclib arm, although the results showed an approximate 46% reduction in relative risk.3 These results put abemaciclib roughly on par with palbociclib and ribociclib in the first-line setting, although cross-trial comparisons are always challenging. This lack of clear superiority for abemaciclib over the alternative CDK4/6 inhibitors presents the potential for preferred contracting.

Abemaciclib’s ability to be dosed continuously could be viewed by some as an advantage over palbociclib or ribociclib, although this is not likely a meaningful difference from a payer contracting perspective. Its flexibility in being paired with either anastrozole or letrozole may be viewed by oncologists as a clinical advantage, as some may prefer one agent over another and this simplifies their management of patients. However, this is likely a small differentiating point from a coverage perspective and not likely to overcome cost considerations.

An important consideration for preferred contracting would be secondary costs related to side effects, particularly grade 3/4 adverse events. Patients treated with abemaciclib have experienced high rates of diarrhea—a tradeoff for any potential gains in efficacy. Most patients’ diarrhea was controlled with nonprescription therapy, limiting the impact of this side effect; however, in MONARCH 3, 8 of 10 patients had diarrhea, with nearly 10% reporting grade 3 diarrhea.2 Whether the significantly lower rates of neutropenia in MONARCH 3 (noted to be 21% grade 3/4 neutropenia2 vs 62% and 59.3%, respectively, for palbociclib and ribociclib),4,5 and the probable routine use of colony-stimulating factor are enough to overcome these concerns is a relevant point of discussion with manufacturers and may be assisted by health economic data revealing the costs incurred by these various complications.

Of greater concern for preferred contracting of abemaciclib is the increased incidence of venous thromboembolism in patients receiving abemaciclib versus placebo (5% vs 1%, respectively).2 The monograph did not indicate this to be a common side effect with either palbociclib or ribociclib, and review of both PALOMA-3 and MONALEESA-2 updated results5,6 also did not demonstrate this to be an issue with either drug. This complicating side effect of abemaciclib could affect a provider’s preference for this therapy and again could affect contracting opportunities because of associated costs that must be taken into account.

In summary, the presence of a third CDK4/6 inhibitor will help achieve health improvements for a subset of the breast cancer population covered by any payer. The current lack of head-to-head data comparing the 3 agents limits the ability to prefer one product over another. Secondary characteristics, such as continuous dosing or ability to prescribe with multiple aromatase inhibitors, are not likely to have a significant impact on formulary preference. Contracting opportunities may exist for abemaciclib to gain market share, but as is most often the case, this is likely to hinge on 3 factors: (1) provider willingness to allow for a preferred agent, (2) pricing considerations, and (3) price protection.


  1. Dieguez G, Ferro C, Pyenson BS. Milliman research report: a multiyear look at the cost burden of cancer. www.milliman.com/uploadedFiles/insight/2017/cost-burden-cancer-care.pdf. Accessed February 19, 2018.
  2. Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35:3638-3646.
  3. ESMO 2017 Press Release: Abemaciclib Initial Therapy Improves Outcome in Endocrine-sensitive Advanced Breast Cancer. www.esmo.org/Conferences/Past-Conferences/ESMO-2017-Congress/Press-Media/Press-Releases/Abemaciclib-Initial-Therapy-Improves-Outcome-in-Endocrine-sensitive-Advanced-Breast-Cancer. Accessed February 21, 2018.
  4. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375:1738-1748.
  5. Turner NC, Ro J, André F, et al. Palbociclib in hormone-receptor–positive advanced breast cancer. N Engl J Med. 2015;373:209-219.
  6. Hortobagyi GN, Stemmer SM, Burris HA, et al. Updated results from MONALEESA-2, a phase 3 trial of first-line ribociclib + letrozole in hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC). J Clin Oncol. 2017;35(suppl 15). Abstract 1038.
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Last modified: August 10, 2023

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