Real-World Outcome and Prognostic Factors Among HER2-Positive Metastatic Breast Cancer Patients Receiving Pyrotinib-Based Therapy: A Multicenter Retrospective Analysis

Figures & data

Table 1 Baseline Characteristics

Characteristics	n (%)
Age (years)
< 65	157 (92.9)
≥ 65	12 (7.1)
ECOG performance status
0~1	151 (89.3)
2	18 (10.7)
Hormone receptor status
ER and PR negative	101 (59.8)
ER and/or PR positive	68 (40.2)
Disease extent at diagnosis
De novo IV stage	21 (12.4)
Recurrent	148 (87.6)
Sites of metastases
Visceral	131 (77.5)
Liver	58 (34.3)
Lung	87 (51.5)
Brain	32 (18.9)
Nonvisceral	38 (22.5)
Lymph nodes	88 (52.1)
Bone	63 (37.3)
Number of metastases
< 3	107 (63.3)
≥ 3	62 (36.7)
Previous anti-HER2 treatment
Yes	158 (93.5)
(Neo) adjuvant setting	47 (27.8)
Metastatic setting	118 (69.8)
No	11 (6.5)
Previous anti-HER2 drugs
Trastuzumab	158 (93.5)
Pertuzumab	9 (5.3)
Lapatinib	4 (2.4)
T-DM1	1 (0.1)
Resistance to trastuzumab
Primary resistance	56 (33.1)
Acquired resistance	92 (54.4)
Non-resistance	21 (12.4)
Lines of anti-HER2 therapy
1	19 (11.2)
2	119 (70.4)
≥ 3	31 (18.3)
Lines of systematic therapy
1	42 (24.9)
2	73 (43.2)
≥ 3	54 (31.9)

Abbreviations: ECOG, eastern cooperative oncology group; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2.

Table 2 Subgroup Analysis of Short-Term Response

Therapy Regimens		Total, n (%)	Response, n (%)				ORR, n (%)	DCR, n (%)
			CR	PR	SD	PD
Total		169	11 (6.5)	99 (58.6)	38 (22.5)	21 (12.4)	110 (65.1)	148 (87.6)
Pyrotinib alone		11 (6.5)	0 (0.0)	7 (63.6)	1 (9.1)	3 (27.3)	7 (63.6)	8 (72.7)
First-line	Anti-HER2 therapy	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
	Systematic therapy	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Second-line	Anti-HER2 therapy	9 (81.8)	0 (0.0)	6 (66.7)	1 (11.1)	2 (22.2)	6 (66.7)	7 (77.8)
	Systematic therapy	6 (54.5)	0 (0.0)	4 (66.7)	0 (0.0)	2 (33.3)	4 (66.7)	4 (66.7)
Third-or-higher-line	Anti-HER2 therapy	2 (18.2)	0 (0.0)	1 (50.0)	0 (0.0)	1 (50.0)	1 (50.0)	1 (50.0)
	Systematic therapy	5 (45.5)	0 (0.0)	3 (60.0)	1 (20.0)	1 (20.0)	3 (60.0)	4 (80.0)
Pyrotinib + Capecitabine		125 (74.0)	10 (8.0)	71 (56.8)	30 (24.0)	14 (11.2)	81 (64.8)	111 (88.8)
First-line	Anti-HER2 therapy	11 (8.8)	2 (18.2)	8 (72.7)	1 (9.1)	0 (0.0)	10 (90.9)	11 (100)
	Systematic therapy	32 (25.6)	6 (18.8)	22 (68.8)	4 (12.5)	0 (0.0)	28 (87.5)	32 (100)
Second-line	Anti-HER2 therapy	89 (71.2)	8 (9.0)	50 (56.2)	20 (22.5)	11 (12.4)	58 (65.2)	78 (87.6)
	Systematic therapy	56 (44.8)	2 (3.6)	31 (55.4)	15 (26.8)	8 (14.3)	33 (58.9)	48 (85.7)
Third-or-higher-line	Anti-HER2 therapy	25 (20.0)	0 (0.0)	13 (52.0)	9 (36.0)	3 (12.0)	13 (52.0)	22 (88.0)
	Systematic therapy	37 (29.6)	2 (5.4)	18 (48.6)	11 (29.7)	6 (16.2)	20 (54.1)	31 (83.8)
Pyrotinib + chemotherapy (non-capecitabine)		16 (9.5)	0 (0.0)	10 (62.5)	3 (18.8)	3 (18.8)	10 (62.5)	13 (81.3)
First-line	Anti-HER2 therapy	3 (18.8)	0 (0.0)	2 (66.7)	1 (33.3)	0 (0.0)	2 (66.7)	3 (100)
	Systematic therapy	3 (18.8)	0 (0.0)	3 (100)	0 (0.0)	0 (0.0)	3 (100)	3 (100)
Second-line	Anti-HER2 therapy	10 (62.5)	0 (0.0)	7 (70.0)	0 (0.0)	3 (30.0)	7 (70.0)	7 (70.0)
	Systematic therapy	6 (37.5)	0 (0.0)	3 (50.0)	0 (0.0)	3 (50.0)	3 (50.0)	3 (50.0)
Third-or-higher-line	Anti-HER2 therapy	3 (18.8)	0 (0.0)	1 (33.3)	2 (66.7)	0 (0.0)	1 (33.3)	3 (100)
	Systematic therapy	7 (43.8)	0 (0.0)	4 (57.1)	3 (42.9)	0 (0.0)	4 (57.1)	7 (100)
Pyrotinib + Trastuzumab (± chemotherapy)		13 (7.7)	1 (7.7)	8 (61.5)	3 (23.1)	1 (7.7)	9 (69.2)	12 (92.3)
First-line	Anti-HER2 therapy	4 (30.8)	1 (25.0)	3 (75.0)	0 (0.0)	0 (0.0)	4 (100)	4 (100)
	Systematic therapy	5 (38.5)	1 (20.0)	4 (80.0)	0 (0.0)	0 (0.0)	5 (100)	5 (100)
Second-line	anti-HER2 therapy	8 (61.5)	0 (0.0)	5 (62.5)	2 (25.0)	1 (12.5)	5 (62.5)	7 (87.5)
	Systematic therapy	5 (38.5)	0 (0.0)	4 (80.0)	1 (20.0)	0 (0.0)	4 (80.0)	5 (100)
Third-or-higher-line	Anti-HER2 therapy	1 (7.7)	0 (0.0)	0 (0.0)	1 (100)	0 (0.0)	0 (0.0)	1 (100)
	Systematic therapy	3 (23.1)	0 (0.0)	0 (0.0)	2 (66.7)	1 (33.3)	0 (0.0)	2 (66.7)
Pyrotinib + Endocrine therapy		4 (2.4)	0 (0.0)	3 (75.0)	1 (25.0)	0 (0.0)	3 (75.0)	4 (100)
First-line	Anti-HER2 therapy	1 (25.0)	0 (0.0)	0 (0.0)	1 (100)	0 (0.0)	0 (0.0)	1 (100)
	Systematic therapy	2 (50.0)	0 (0.0)	1 (50.0)	1 (50.0)	0 (0.0)	1 (50.0)	2 (100)
Second-line	Anti-HER2 therapy	3 (75.0)	0 (0.0)	3 (100)	0 (0.0)	0 (0.0)	3 (100)	3 (100)
	Systematic therapy	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Third-or-higher-line	anti-HER2 therapy	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
	Systematic therapy	2 (50.0)	0 (0.0)	2 (100)	0 (0.0)	0 (0.0)	2 (100)	2 (100)

Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate; HER2, human epidermal growth factor receptor 2.

Figure 1 Kaplan–Meier curves of PFS for patients.

Notes: (A) Overall cohort. (B) Patients treated with pyrotinib combined with capecitabine as second-line anti-HER2 therapy. (C) Patients stratified by lines of anti-HER2 therapy. (D) Patients stratified by lines of systematic therapy.

Figure 2 Kaplan–Meier curves of PFS for patients treated with different regimens.

Notes: (A) Patients treated with pyrotinib alone or combined regimens. (B) Patients treated with pyrotinib combined with capecitabine or other chemotherapeutic drugs (non-capecitabine). (C) Patients treated with single (pyrotinib) or dual anti-HER2 (pyrotinib combined with trastuzumab) therapy.

Figure 3 Kaplan–Meier curves of PFS for patients with different characteristics.

Notes: (A) Patients stratified by HR status according to pathological characteristics. (B) Patients stratified by pertuzumab-treated or pertuzumab-naive according to prior treatment history. (C) Patients stratified by sensitivity to trastuzumab according to prior treatment history. (D) Patients stratified by liver metastasis according to clinical characteristics. (E) Patients stratified by brain metastasis according to clinical characteristics. (F) Patients stratified by number of metastatic sites according to clinicopathological characteristics.

Abbreviation: HR, hormone receptor.

Table 3 Adverse Events

Adverse Events	All Grade, n (%)	Grade 1~2, n (%)	Grade 3~4, n (%)
Diarrhea	149 (88.2)	122 (72.2)	27 (16.0)
Hand-foot syndrome	60 (35.5)	51 (30.2)	9 (5.3)
Vomiting	46 (27.2)	40 (23.7)	6 (3.6)
Anemia	45 (26.6)	35 (20.7)	10 (5.9)
Leukopenia	42 (24.9)	39 (23.1)	3 (1.8)
Nausea	39 (23.1)	35 (20.7)	4 (2.4)
Hypokalemia	37 (21.9)	26 (15.4)	11 (6.5)
Neutropenia	33 (19.5)	29 (17.2)	4 (2.4)
Creatinine increased	31 (18.3)	30 (17.8)	1 (0.1)
Anorexia	29 (17.2)	25 (14.8)	4 (2.4)
Blood bilirubin increased	24 (14.2)	24 (14.2)	0 (0)
Rash	21 (12.4)	19 (11.2)	2 (1.2)
Aminotransferase increased	18 (10.7)	15 (8.9)	3 (1.8)
Mucositis oral	16 (9.5)	15 (8.9)	1 (0.1)
Hypertriglyceridemia	13 (7.7)	12 (7.1)	1 (0.1)
Thrombocytopenia	10 (5.9)	7 (4.1)	3 (1.8)
Cholesterol high	6 (3.6)	6 (3.6)	0 (0)

Figure 4 Exploration of potential factors or biomarkers influencing efficacy and outcome of pyrotinib-based therapy.

Notes: (A) The objective response rate for patients stratified by diarrhea grade. (B) PFS for patients stratified by diarrhea grade. (C) The objective response rate for patients stratified by VEGF-A expression level. (D) PFS for patients stratified by VEGF-A expression level.

Abbreviation: VEGF-A, vascular endothelial growth factor A.

Figure 5 Cox regression analyses of PFS in 50 HER2-positive MBC patients with baseline detection of VEGF-A.

Notes: (A) Forest plot of univariate Cox regression analyses. (B) Forest plot of multivariate Cox regression analyses.

Abbreviations: ECOG, eastern cooperative oncology group; HR positive, hormone receptor positive; HER2, human epidermal growth factor receptor 2; VEGF-A, vascular endothelial growth factor A; Adjust HR (95% CI), Adjust hazard ratios (95%confidence interval).