Comparative efficacy &amp; safety of buparlisib plus fulvestrant, fulvestrant plus dalpiciclib, and ribociclib plus letrozole for postmenopausal, hormone receptor-positive, and HER2-negative breast cancer

Liu, Qi; Hou, Lingli; Zhao, Ying; Yang, Hongwei; Mo, Zhengying; Yu, Fei

doi:10.1016/j.clinsp.2023.100291

Acessibilidade / Reportar erro

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Original articles • Clinics 78 • 2023 • https://doi.org/10.1016/j.clinsp.2023.100291 copy

Comparative efficacy & safety of buparlisib plus fulvestrant, fulvestrant plus dalpiciclib, and ribociclib plus letrozole for postmenopausal, hormone receptor-positive, and HER2-negative breast cancer

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objectives:

This study aimed to compare progression-free survival, overall survival, clinical benefits, and adverse effects in postmenopausal women with hormone receptor-positive and HER2-negative breast cancer who received buparlisib plus fulvestrant against those of women who received dalpiciclib plus fulvestrant, considering ribociclib plus letrozole treatment as the reference standard.

Methods:

Women received buparlisib plus fulvestrant (BF cohort, n = 108), dalpiciclib plus fulvestrant (DF cohort, n = 132), or ribociclib plus letrozole (RL cohort, n = 150) until unacceptable toxicity was observed.

Results:

A total of 117 (89 %), 80 (74 %), and 84 (56 %) women in the BF, DF, and RL cohorts, respectively, had clinical benefits. After treatment, the clinical benefits for women and after 42 months of follow-up progression-free survival and overall survival were higher in the DF cohort than in the BF and RL cohorts (p < 0.05 for all). Neutropenia, vomiting, constipation, nausea, diarrhea, and anorexia were reported higher in women of the DF and BF cohorts than in women of the RL cohort. Leukopenia and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the RL cohort than in women in the DF and BF cohorts. Depression, anxiety, and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the BF cohort than in women in the DF and RL cohorts.

Conclusions:

Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

Keywords:
Breast cancer; Buparlisib; Dalpiciclib; Endocrine therapy; Fulvestrant; Letrozole; Ribociclib

Highlights

Dalpiciclib + fulvestrant is effective in hormone (+) and HER2 (−) breast cancers.
Dalpiciclib and buparlisib cause neutropenia.
Gastrointestinal tract-related adverse effects while treatment with fulvestrant.
Liver function monitoring is recommended for ribociclib + letrozole treatment.
Women should be under the supervision of a consultant while 100 mg/day of buparlisib.

Parameters	Total	Cohorts			Comparisons between cohorts
Treatments	–	BF Buparlisib+fulvestrant	DF Dalpiciclib+fulvestrant	RL Ribociclib+letrozole
Women	390	108	132	150	p-value	df	Test value
Age (years)	58.35±5.36	58.08±4.57	57.92±5.63	58.91±5.62	0.2485 (one-way ANOVA)	389	1.397
Ethnicity
Han Chinese	343 (90)	98 (91)	120 (90)	135 (90)	0.9993 (χ²-test)	6	0.3361
Mongolian	30 (8)	8 (7)	10 (8)	12 (8)
Tibetan	4 (1)	1 (1)	1 (1)	2 (1)
Uyghurs Muslim	3 (1)	1 (1)	1 (1)	1 (1)
^a a 0: Fully active, 1: Restricted in strenuous activity, and ≥ 2: Increasing disability. All results were significant if p < 0.05.ECOG, Eastern Cooperative Oncology Group; ANOVA, Analysis of variance; χ2-test, Chi-Square test for independence; df, Degree of freedom. Test value (F-value for ANOVA; χ2-value or χ2-test). ECOG performance status
0	210 (54)	60 (55)	70 (51)	80 (54)	0.9918 (χ²-test)	6	0.81
1	161 (41)	42 (39)	56 (42)	63 (42)
2	15 (4)	5 (5)	5 (4)	5 (3)
3	4 (1)	1 (1)	1 (1)	2 (1)

Parameters	Cohorts					Comparison between BF and RL
Treatments	DF Dalpiciclib+fulvestrant	BF Buparlisib+fulvestrant		RL Ribociclib+letrozole		@
Women 132	108	^a a Concerning the DF value. Fischer exact test was used for statistical analyses. RECIST version 1.1 criteria was used for evaluation of clinical benefits. All results were significant if p < 0.05.95 % CI, 95 % Confidence Interval (using the approximation of Katz.). p-value	150	^a a Concerning the DF value. Fischer exact test was used for statistical analyses. RECIST version 1.1 criteria was used for evaluation of clinical benefits. All results were significant if p < 0.05.95 % CI, 95 % Confidence Interval (using the approximation of Katz.). p-value	p-value
Women with clinical benefit 117 (89)	80 (74)	0.004 (95 % CI 1.114 to 2.603)	84 (56)	<0.0001 (95 % CI: 1.961 to 5.038)	0.0038 (95 % CI: 1.157 to 2.319)

Events	Cohorts							Comparison between BF and RL
Treatments	DF Dalpiciclib+fulvestrant	BF Buparlisib+fulvestrant			RL Ribociclib+letrozole			@	@
Women	132	108	^a a Concerning the DF value. Fischer exact test was used for statistical analyses. All results were significant if p < 0.05.95 % CI, 95 % Confidence Interval (using the approximation of Katz.). p-value	95 % CI	150	^a a Concerning the DF value. Fischer exact test was used for statistical analyses. All results were significant if p < 0.05.95 % CI, 95 % Confidence Interval (using the approximation of Katz.). p-value	95 % CI	p-value	95 % CI
Neutropenia	115 (87)	99 (92)	0.301	0.6051 to 1.116	105 (70)^b b Significant difference concerning the DF value. , ^c c Significant difference concerning the BF value.	0.0005	1.247 to 2.914	<0.0001	1.577 to 5.375
Leukopenia	114 (86)	98 (91)	0.3194	0.6178 to 1.133	142 (95)^b b Significant difference concerning the DF value.	0.0221	0.4811 to 0.8601	0.2284	0.4731 to 1.142
Anemia	117 (89)	97 (90)	0.8367	0.6671 to 1.346	141 (94)	0.1349	0.5176 to 1.017	0.2431	0.4844 to 1.134
Thrombocytopenia	118 (89)	95 (88)	0.8379	0.7284 to 1.567	141 (94)	0.1926	0.5255 to 1.066	0.1133	0.4654 to 0.9971
Lymphopenia	119 (90)	94 (87)	0.539	0.7706 to 1.747	142 (95)	0.176	0.5134 to 1.057	0.041	0.4399 to 0.8906

Events	Cohorts
Treatments	DF Dalpiciclib+fulvestrant	BF Buparlisib+fulvestrant			RL Ribociclib+letrozole			Comparison between BF and RL
Women	132	108	^a a Concerning the DF value. Fischer exact test was used for statistical analyses. All results were significant if p < 0.05.95 % CI, 95 % Confidence Interval (using the approximation of Katz.). p-value	95 % CI	150	^a a Concerning the DF value. Fischer exact test was used for statistical analyses. All results were significant if p < 0.05.95 % CI, 95 % Confidence Interval (using the approximation of Katz.). p-value	95 % CI	p-value	95 % CI
Headache	25 (19)	17 (16)	0.6092	0.8320 to 1.458	25 (17)	0.642	0.7950 to 1.478	0.8662	0.6448 to 1.432
Vomiting	27 (20)	22 (20)	0.9999	0.7549 to 1.331	21 (14)	0.1569	0.9407 to 1.671	0.1807	0.9151 to 1.788
Cough	14 (11)	11 (10)	0.9999	0.7061 to 1.474	16 (11)	0.9999	0.6650 to 1.494	0.9999	0.6006 to 1.567
Constipation	25 (19)	21 (19)	0.9999	0.7346 to 1.322	16 (11)	0.0622	1.035 to 1.822	0.0707	1.041 to 1.996
Insomnia	13 (10)	10 (9)	0.9999	0.7060 to 1.505	16 (11)	0.847	0.6234 to 1.457	0.8348	0.5473 to 1.515
Arthralgia	14 (11)	9 (8)	0.6612	0.7891 to 1.588	17 (11)	0.9999	0.6378 to 1.447	0.5312	0.4685 to 1.405
Back pain	15 (11)	12 (11)	0.9999	0.7065 to 1.448	20 (13)	0.7182	0.6037 to 1.356	0.7028	0.5504 to 1.416
Nausea	35 (27)	28 (26)	0.9999	0.7830 to 1.313	34 (23)	0.4892	0.8460 to 1.467	0.5579	0.8018 to 1.527
Hyperglycemia	22 (17)	27 (25)	0.147	0.5586 to 1.088	43 (29)^b b Significant difference concerning the DF value.	0.023	0.4638 to 0.9613	0.5713	0.6383 to 1.256
Increased alanine aminotransferase	25 (19)	17 (16)	0.9999	0.7093 to 1.367	40 (27)^b b Significant difference concerning the DF value. , ^c c Significant difference concerning the BF value.	0.0127	0.4293 to 0.9408	0.0475	0.4301 to 1.009
Increased aspartate aminotransferase	31 (23)	21 (19)	0.5293	0.8555 to 1.439	41 (27)	0.4955	0.6628 to 1.209	0.1836	0.5210 to 1.118
Diarrhea	35 (27)	35 (32)	0.3224	0.6702 to 1.146	35 (23)	0.5817	0.8289 to 1.441	0.1194	0.9586 to 1.730
Rash	25 (19)	25 (23)	0.43	0.6550 to 1.204	41 (27)	0.1209	0.5458 to 1.071	0.4728	0.6181 to 1.242
Fatigue	45 (34)	50 (46)	0.0636	0.6147 to 1.014	75 (50)^b b Significant difference concerning the DF value.	0.008	0.5321 to 0.9163	0.614	0.6871 to 1.225
Depression	2 (1)	15 (14)^b b Significant difference concerning the DF value.	0.0002	0.05462 to 0.7456	5 (3)^c c Significant difference concerning the BF value.	0.454	0.1860 to 1.963	0.0035	1.424 to 2.588
Anxiety	5 (4)	20 (19)^b b Significant difference concerning the DF value.	0.0002	0.1534 to 0.7476	10 (7)^c c Significant difference concerning the BF value.	0.3039	0.3388 to 1.450	0.0052	1.278 to 2.335
Anorexia	62 (47)	85 (79)^b b Significant difference concerning the DF value.	<0.0001	0.4487 to 0.6999	55 (37)^c c Significant difference concerning the BF value.	0.0904	0.9762 to 1.598	<0.0001	2.108 to 4.602
Dysgeusia	5 (4)	20 (19)^b b Significant difference concerning the DF value.	0.0002	0.1534 to 0.7476	14(9)^c c Significant difference concerning the BF value.	0.0938	0.2541 to 1.169	0.0398	1.082 to 2.072

Faculdade de Medicina / USP Rua Dr Ovídio Pires de Campos, 225 - 6 and., 05403-010 São Paulo SP - Brazil, Tel.: (55 11) 2661-6235 - São Paulo - SP - Brazil
E-mail: clinics@hc.fm.usp.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] *Corresponding author. E-mail address: 845430552@qq.com (L. Hou).