Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice

Abstract

Background: Findings from randomized clinical trials may have limited generalizability to patients treated in routine clinical practice. This study examined the effectiveness of first-line palbociclib plus letrozole versus letrozole alone on survival outcomes in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-negative (HER2-) metastatic breast cancer (MBC) treated in routine clinical practice in the USA.

Patients and methods: This was a retrospective observational analysis of electronic health records within the Flatiron Health Analytic Database. A total of 1430 patients with ≥ 3 months of follow-up received palbociclib plus letrozole or letrozole alone in the first-line setting between February 3, 2015, and February 28, 2019. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. Real-world progression-free survival (rwPFS) and overall survival (OS) were analyzed.

Results: After sIPTW adjustment, median follow-up was 24.2 months (interquartile range [IQR], 14.2-34.9) in the palbociclib group and 23.3 months (IQR, 12.7-34.3) in those taking letrozole alone. Palbociclib combination treatment was associated with significantly longer median rwPFS compared to letrozole alone (20.0 vs 11.9 months; hazard ratio [HR], 0.58; 95% CI, 0.49-0.69; P < 0.0001). Median OS was not reached in the palbociclib group and was 43.1 months with letrozole alone (HR, 0.66; 95% CI, 0.53-0.82; P = 0.0002). The 2-year OS rate was 78.3% in the palbociclib group and 68.0% with letrozole alone. A propensity score matching analysis showed similar results.

Conclusions: In this "real-world" population of patients with HR+/HER2- MBC, palbociclib in combination with endocrine therapy was associated with improved survival outcomes compared with patients treated with letrozole alone in the first-line setting.

Trial registration: Clinicaltrials.gov; NCT04176354.

Keywords: Comparative effectiveness; HR+/HER2−; Letrozole; Metastatic breast cancer; Palbociclib; Real-world data.

Conflict of interest statement

ADeM has received consulting fees from Pfizer Inc. and Context Therapeutics, honoraria from Pfizer Inc., and research funding from Pfizer, Novartis, Menarini Biosystems, Calithera, Incyte, and Genetech. MC has received consulting fees from Novartis, Merus, CytoDyn, Sermonix, and G1 Therapeutics; honoraria from Pfizer Inc.; and research funding from Pfizer Inc., Novartis, Merus, Lilly, and G1 Therapeutics. AB has received consulting fees from Pfizer Inc. JM is a former employee of and owns stock in Pfizer Inc. RML has received research funding from Pfizer Inc., Novartis, Eli Lilly, GlaxoSmithKline, and Zentalis and consulting fees from Pfizer Inc. and Novartis. MAT has received research funding from Pfizer Inc. and Genentech, honorarium from MJH Life Sciences, and advisory fees from the Centers for Disease Control. HSR has received research funding from Plexxikon, Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Eli Lilly, Genentech, and Merck. RSF has received consulting fees and honoraria from Pfizer Inc. and research funding from Pfizer Inc., Eli Lilly, and Novartis. XL, LMcR, and BE are employees of and own stock in Pfizer Inc.

Figures

Fig. 1

Kaplan-Meier curves of real-world progression-free survival in a the unadjusted analysis (number of patients at risk are shown), b sIPTW-adjusted analysis (number of patients at risk are shown), and c after PSM. LET, letrozole; NR, not reached; PAL, palbociclib; PSM, propensity score matching; rwPFS, real-world progression-free survival; sIPTW, stabilized inverse probability of treatment weighting

Fig. 2

Forest plot of real-world progression-free survival by subgroup* after sIPTW. Dx, diagnosis; ECOG PS, Eastern Cooperative Oncology Group performance status; LET, letrozole; ND, not documented; PAL, palbociclib; sIPTW, stabilized inverse probability of treatment weighting. *Race by Cohort interaction was the only subgroup variable-by-treatment cohort interaction that was significant (P=0.0010); however, race data were not known in the “not documented” race group.†Bone-only disease was defined as metastatic disease in the bone only.‡Visceral disease was defined as metastatic disease in the lung and/or liver; patients could have had other sites of metastases. No visceral disease was defined as no lung or liver metastases. The total patient population for different subgroups varied due to the application of sIPTW. Therefore, the total n number for each subgroup may not have always equaled the N number of the treatment arm (due to rounding error and categorization differences)

Fig. 3

Kaplan-Meier curves of overall survival in a the unadjusted analysis (number of patients at risk are shown), b sIPTW-adjusted analysis (number of patients at risk are shown), and c after PSM. LET, letrozole; NE, not estimable; NR, not reached; OS, overall survival; PAL, palbociclib; PSM, propensity score matching; sIPTW, stabilized inverse probability of treatment weighting

Fig. 4

Forest plot of overall survival by subgroup* after sIPTW. Dx, diagnosis; ECOG PS, Eastern Cooperative Oncology Group performance status; LET, letrozole; ND, not documented; PAL, palbociclib; sIPTW, stabilized inverse probability of treatment weighting. *Race by Cohort interaction and Metastatic Sites by Cohort interaction were the only subgroup variable-by-treatment cohort interaction that were significant (P<0.0001 and P=0.0050, respectively); however, race data were not known in the “not documented” race group.†Bone-only disease was defined as metastatic disease in the bone only.‡Visceral disease was defined as metastatic disease in the lung and/or liver; patients could have had other sites of metastases. No visceral disease was defined as no lung or liver metastases. The total patient population for different subgroups varied due to the application of sIPTW. Therefore, the total n number for each subgroup may not have always equaled the N number of the treatment arm (due to rounding error and categorization differences)