Real-world effectiveness of palbociclib in HR+/HER2- metastatic breast cancer: a literature review

Figures & data

Table 1. Search strategy.

	BLOCK 1	BLOCK 2	BLOCK 3	BLOCK 4	BLOCK 5
Subject/keyword	Breast cancer	ER-positive	Metastasis	CDK 4/6 inhibitors	Real-world
MeSH	“Breast neoplasm” [MeSH]	“Receptors, Estrogen” [MeSH]	“Neoplasm metastasis” [MeSH]	“Cyclin-dependent kinase inhibitor proteins” [MeSH] OR “Palbociclib” [Supplementary concept] OR “Abemaciclib” [Supplementary concept] OR “Ribociclib” [Supplementary concept]
	Search #1	Search #4	Search #7	Search #10
Free text	“Breast neoplasm*” OR “Breast cancer” OR “Mamma cancer” OR “Cancer in breast*” OR “Cancer of breast*” OR “Cancer mamma*” OR “Mammary cancer*” OR “Mammary neoplasm*” OR “Breast tumor*” OR “Breast malignant tumor*”	”ER positive” OR “ER-positive” OR “ER+” OR “HR positive” OR “HR-positive” OR “HR+” OR “Estrogen receptor positive” OR “Hormone receptor positive” OR “HR+/HER2-” OR “ER+/HER2-” OR “Oestrogen receptor positive”	“Advanced” OR “Metastasis” OR “Metastase*” OR “Metastatic”	“CDK 4/6 inhibit*” OR “Cyclin-dependent kinase 4/6 inhibit*” OR “Inhibitor* of cyclin-dependent kinase 4/6” OR “Palbociclib” OR “Ibrance” OR “Ribociclib” OR “Kisqali” OR “Abemaciclib” OR “Verzenio”	“Real-world” OR “RWD” OR “RWE” OR “Real-life data” OR “Clinical outcome*” OR “Real-world setting*” OR “Real-world stud*” OR “Real-world clinical practice” OR “Electronic health records”
	Search #2	Search #5	Search #8	Search #11	Search #13
	Search #3 = #1 OR #2	Search #6 = #4 OR #5	Search #9 = #7 OR #8	Search #12 = #10 OR #11	Search #13

Final search = #3 AND #6 AND #9 AND #12 AND #13.

Figure 1. Flow chart of the study selection process.

Table 2. Comparative studies.

Study (year)	Line of treatment	Treatment regimen	Patients (n)			Follow-up (months)	Median PFS (months [95% CI])			Median OS (months [95% CI])			Ref.
			Unadjusted	sIPTW	PSM	sIPTW	Unadjusted	sIPTW	PSM	Unadjusted	sIPTW	PSM
Rugo et al. (2022)	1st line	PAL + AI vs AI	1324/1564	1572/1137	939/939	23.9/24.5	19.8 (17.9–21.7)/13.9 (12.7–15.2)	19.3 (17.5–20.7)/13.9 (12.5–15.2) HR: 0.70 (0.62–0.78), p < 0.0001	19.8 (17.3–21.9)/14.9 (12.9–16.9)	53.4 (48.7–58.6)/40.4 (36.3–44.9)	49.1 (45.2–57.7)/43.2 (37.6–48.0) HR: 0.76 (0.65–0.87), p < 0.0001	57.8 (47.2–NE)/43.5 37.6–48.9)	[20]
DeMichele et al. (2021)	1st line	PAL + LET vs LET	772/658	839/698	464/464	24.2/23.3	19.7 (17.3–21.9)/11.9 (10.5–13.5)	20.0 (17.5–21.9)/11.9 (10.5–13.7) HR: 0.58 (0.49–0.69), p < 0.0001	20.2 (18.2–23.7)/11.9 (10.4–14.5)	NR (NE–NE)/40.3 (34.2–NE)	NR (NE–NE)/43.1 (34.3–NE) HR: 0.66 (0.53–0.82), p = 0.0002	NR (NE–NE)/43.1 (34.2–NE)	[21]
Brufsky et al. (2022)	1st line	PAL + LET vs LET (patients with lung and/or liver metastasis)	330/221	321/269	194/194	22.6/22.1	15.4 (12.5–19.5)/10.2 (8.0–11.7)	16.1 (13.0–20.2)/9.6 (7.2–11.0) HR: 0.56 (0.45–0.69), p < 0.001	15.7 (12.7–20.2)/9.5 (6.7–10.8)	NR (38.3–NR)/29.4 (25.8–40.8)	NR (38.3–NR)/32.4 (26.0–40.8) HR: 0.58 (0.43–0.77), p < 0.001	NR (42.7–NR)/29.1 (25.3–40.8)	[22]
Ha et al. (2022)	1st line	PAL + AI vs AI	778/2452		708/708	PSM: 30.0/119			17.4 (15.9–20.0)/11.1 (9.9–13.6) HR: 0.71 (0.64–0.8), p < 0.0001			44.3 (41.5–NA)/40.2 (37.9–44.2) HR: 1.0 (0.8–1.23), p = 1	[23]
	2nd line	PAL + FVT vs FVT (after previously having progressed on an AI in metastatic setting)	410/1183		310/310	PSM: 30.1/105.7			10.0 (8.4–11.8)/5.0 (4.4–5.9) HR: 0.51 (0.41–0.64), p < 0.0001			32.3 (28.1–37.4)/24.6 (21.8–27.7) HR: 0.67 (0.52–0.87), p < 0.0022

Bold values indicate the values/results presented and discussed in the article.

AI: Aromatase inhibitor; FVT: Fulvestrant; LET: Ietrozole; NE: Not estimable; NR: Not reached PAL: Palbociclib.

Table 3. Single arm studies.

Study (year)	Line of treatment	Treatment regimen	Patients (n)	Follow-up (months)	Median PFS (months [95% CI])	Median OS (months [95% CI])	Ref.
Porte et al. (2020)	1st line	PAL + AI or FVT	225	20.7	23.0 (20.8–NR)	NR	[24]
	2nd line	PAL + AI or FVT	85	20.7	13.1 (9.0–18.6)	NR
Law et al. (2022)	1st line	PAL + AI	242	22.4	31.7 months (27.9–NE)	NR	[25]

AI: Aromatase inhibitor; FVT: Fulvestrant; LET: letrozole; NA: Not achieved; NR: Not reached; PAL: Palbociclib.

Rugo HS, Brufsky A, Liu X et al. Real-world study of overall survival with palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer. NPJ Breast Cancer 8(1), 114 (2022).

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Demichele A, Cristofanilli M, Brufsky A et al. Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice. Breast Cancer Res. 23(1), 37 (2021).

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Brufsky A, Liu X, Li B, Mcroy L, Layman RM. Real-world effectiveness of palbociclib plus letrozole vs letrozole alone for metastatic breast cancer with lung or liver metastases: flatiron database analysis. Front. Oncol. 12, 865292 (2022).

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Ha MJ, Singareeka Raghavendra A, Kettner NM et al. Palbociclib plus endocrine therapy significantly enhances overall survival of HR+/HER2- metastatic breast cancer patients compared to endocrine therapy alone in the second-line setting: a large institutional study. Int. J. Cancer 150(12), 2025–2037 (2022).

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Porte B, Carton M, Lerebours F et al. Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer. Breast 54, 303–310 (2020).

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Law JW, Mitra D, Kaplan HG et al. Real-world treatment patterns and clinical effectiveness of palbociclib plus an aromatase inhibitor as first-line therapy in advanced/metastatic breast cancer: analysis from the US syapse Learning health network. Curr. Oncol. 29(2), 1047–1061 (2022).

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