Real-world clinical outcome and toxicity data and economic aspects in patients with advanced breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy: the experience of the Hellenic Cooperative Oncology Group

Abstract

Background: We evaluated real-world clinical outcomes and toxicity data and assessed treatment-related costs in patients with advanced breast cancer who received treatment with cyclin-dependent kinase inhibitors (CDKi).

Patients and methods: We conducted a prospective-retrospective analysis of patients with advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who received a CDKi, in combination with endocrine therapy, at any line of treatment. The primary endpoint was progression-free survival (PFS). Cost analysis was conducted from a public third-payer (National Organization for Healthcare Services Provision (EOPYY)) perspective, assessing only costs related to direct medical care, including drug therapy costs and adverse drug reaction (ADR)-related costs.

Results: From July 2015 to October 2019, 365 women received endocrine therapy combined with CDKi; median age was 61 years, postmenopausal 290 (80.6%) patients. CDKi were administered as first-line treatment in 149 (40.9%) patients, second-line treatment in 96 (26.4%) and third-line treatment and beyond in 119 (32.7%) patients. The most common adverse events were neutropenia, anaemia, thrombocytopenia and fatigue. Grade 3-4 adverse events occurred in 86 (23.6%) patients, whereas 8 (2.2%) patients permanently discontinued treatment due to toxicity. The median PFS for patients who received CDKi as first-line, second-line and third-line treatment and beyond was 18.7, 12 and 7.4 months, respectively. The median overall survival since the initiation of CDKi treatment was 29.9 months (95% CI: 23.0-not yet reached (NR)). The mean pharmaceutical therapy cost estimated per cycle was 2 724.12 € for each patient, whereas the main driver of the ADR-related costs was haematological adverse events.

Conclusions: Treatment with CDKi was well tolerated, with a low drug discontinuation rate. Patients who received CDKi as first-line treatment had improved PFS and OS compared with second-line treatment and beyond. The main component of direct medical costs assessed in the cost analysis comprises CDKi pharmaceutical therapy costs.

Trial registration number: NCT04133207.

Keywords: aromatase inhibitors; endocrine treatment; health economics; hormone receptor-positive; real-world evidence.

Conflict of interest statement

Competing interests: EF: stock ownership: GENPREX INC, ARIAD and Deciphera Pharmaceuticals, Inc. Travel grant: Merck, Pfizer and K.A.M Oncology/Hematology. Advisory: LEO Pharma. Speaker fees: Roche and Pfizer. AV: advisory boards: Angelini and Takeda. Speaker fees: Bristol-Myers Squibb, Roche and MSD. Training programmes: Astellas, Genesis Pharma, Pfizer, LEO, Abbvie and TEVAAN. Travel fees: Pfizer, Merck, Hospira, Sanofi, Roche, Astra Zeneca, Kyowa Kirin-Anabiosis and Rafarm. AB: advisory role and honorarium: Pfizer and Novartis. SK: consultation/advisory: Astra Zeneca and Roche. Research: Novartis and Roche. Speaker: Astra Zeneca, Novartis and Roche. IB: advisory board: Pfizer and Novartis. Educational grant: Pfizer. Research Fund: Novartis and Lilly. AN: advisory board and speaker fees: Pfizer and Novartis. GA: advisory boards: Novartis, BMS, Roche Hellas, Astra Zeneca, Sanofi, Amgen, Genesis Pharma, Merck and Pfizer. AP: consultation fees: Amgen, Merck Serono, Roche, BMS, Astra Zeneca and MSD. Honoraria: Amgen, Merck Serono, Roche, BMS, Astra Zeneca and MSD. Research funds: BMS and Kura. AK: advisory role: Genesis Pharma. Honoraria: Pfizer. Speaker’s bureau: Roche. Research funding: Merck. Travel: MSD. Educational grants: Novartis, Pfizer, Merck, Roche, BMS, MSD, Genesis and Ipsen. GM: honoraria/consultancy: Astra Zeneca, Roche, Pfizer, BMS, MSD, Takeda, Boehringer, Merck, Novartis and Amgen. Travel fees: Astra Zeneca, Roche, Pfizer, BMS, MSD, Takeda, Boehringer, Merck, Novartis, Astellas and Pierre Fabre. ER: consulting or advisory role: Astra Zeneca, Bristol-Myers Squibb and Pfizer. Research funding: Novartis, Demo Pharmaceutical, EORTC, Radius Pharmaceuticals, Tesaro, Parexel and Anabiosis Pharmaceuticals. Travel: Sanofi, Ipsen, Genesis Pharmaceuticals, LEO Pharma, Merck, Roche and Genekor. GF: advisory board: Pfizer, Sanofi and Roche. Honoraria: Astra Zeneca. Stock ownership: ARIAD and GENPREX. The rest of the authors declare no conflict of interest.

© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ on behalf of the European Society for Medical Oncology.

Figures

Figure 1

(A) Proportion of patients who received treatment with CDKi according to the line of therapy and year of treatment initiation. (B) Dose modification and treatment discontinuation rates in patients who received CDKi. CDKi, cyclin-dependent kinase inhibitor.

Figure 2

(A) Progression-free survival (PFS) rates in all patients of the study. (B) PFS by the line of treatment. (C) Overall survival (OS) rates in all patients of the study. (D) OS by the line of treatment. Two patients who received CDKi in combination with tamoxifen were excluded from the OS and PFS analyses. CDKi, cyclin-dependentkinase inhibitor; NE, not evaluable.