Cisplatin improves antitumor activity of weekly nab-paclitaxel in patients with metastatic breast cancer

Figures & data

Table 1 Patient characteristics (n=73)

Characteristics	Number	%
Age (years)
Median	49
Range	33–65
Amenorrhea
Premenopausal	29	39.7
Postmenopausal	44	60.3
Radical mastectomy
No	5	6.8
Yes	68	93.2
Time to first relapse (years)
Median	2.55
Range	0.4–17
Number of metastatic sites
One	15	20.5
Two	24	32.9
Three or more	34	46.6
Metastatic sites
Visceral	59	80.8
Lung	40	54.8
Liver	27	37.0
Nonvisceral	14	19.2
Bone	23	31.5
Subgroups
Luminal type	46	63.0
Human epidermal growth factor receptor 2-positive	8	11.0
Triple-negative	16	21.9
Unknown	3	4.1
Lines of chemotherapy
First-line	36	49.3
Second-line	28	38.4
Third- or more line	9	12.4
Prior chemotherapy
Adjuvant/neoadjuvant (n=68)
Anthracycline-containing	53	72.6
Taxane-containing	34	50.0
Both	27	39.7
Chemotherapy for MBC (n=37)
Anthracycline-containing	6	16.2
Taxane-containing	12	32.4
Both	3	8.1

Table 2 Treatment efficacy assessed by investigators

Variable	N	Overall response rate	P-value	Median progression-free survival (months) [95% confidence interval]	P-value	Median overall survival (months) [95% confidence interval]	P-value
Whole group	73	67.1%		9.8 [8.1–11.6]		26.9 [22.4–31.4]
Lines of treatment			0.043		0.005		0.178
First-line	36	80.6%		11.7 [10.4–13]		Not reached
Second-line	28	57.1%		7.7 [4.1–11.2]		23.4 [13.7–33.1]
Third- or more line	9	44.4%		7.6 [4.1–11.0]		25.0
Molecular subtypes			0.912		0.323		0.711
Luminal	46	67.4%		8.9 [7.4–10.4]		26.0 [21.5–30.5]
Her-2-positive	8	75.0%		8.2 [0–30.1]		Not reached
Triple-negative	16	68.8%		10.3 [9.9–10.7]		22.5
Prior taxane			0.076		0.009		0.000
Yes	43	58.1%		8.5 [6.0–11.0]		16.7 [11.5–22.0]
No	30	80.0%		11.2 [9.4–13.0]		Not reached

Table 3 Comparison between investigator and independent radiology review

Variable	Investigator review	Independent radiology review
Overall response rate	67.1%	68.5%
Complete response	9.6%	6.8%
Partial response	57.5%	61.6%
Stable disease	16.4%	26.0%
Progressive disease	16.4%	5.5%
Overall response rate by lines of chemotherapy
First-line	80.6%	77.8%
Second-line	57.1%	57.1%
Third- or more lines	44.4%	66.7%
Overall response rate by molecular subtypes
Luminal	67.4%	60.9%
Her-2-positive	75.0%	87.5%
Triple negative	68.8%	87.5%
Median progression-free survival	9.8 months	9.3 months
First-line	11.7 months	11.7 months
Second-line	7.7 months	6.6 months
Third- or more lines	7.6 months	7.6 months

Figure 1 Kaplan–Meier curves for overall survival (A) and analysis of overall survival stratified by taxane pretreatment (B), assessed by investigators.

Abbreviations: OS, overall survival; CI, confidence interval.

Figure 2 Kaplan–Meier curves for progression-free survival. For all patients, investigator assessment (A) and independent review (B). For patients stratified by lines of therapy, investigator assessment (C) and independent review (D). For patients stratified by taxane pretreatment, investigator assessment (E) and independent review (F).

Abbreviations: CI, confidence interval; PFS, progression-free survival.

Table 4 Treatment-related toxicities by grade (n=73)

Toxicity	Grade 1		Grade 2		Grade 3		Grade 4
	No	%	No	%	No	%	No	%
Hematologic
Neutropenia	1	1.4	9	12.3	16	21.9	46	63.0
Leukopenia	2	2.7	15	20.5	39	53.4	16	21.9
Febrile neutropenia					9	12.3	0	0
Thrombocytopenia	6	8.2	9	12.3	1	1.4	0	0
Anemia	11	15.1	44	60.3	10	13.7	3	4.1
Nonhematologic
Rash	19	26.0	7	9.6	1	1.4	0	0
Peripheral neuropathy	16	21.9	18	24.7	19	26.0	0	0
Alopecia	31	42.5	42	57.5
Fatigue	22	30.1	3	4.1	0	0	0	0
Nausea	34	46.6	11	15.1	2	2.7	0	0
Vomiting	31	42.5	12	16.4	2	2.7	0	0
Diarrhea	2	2.7	5	6.8	2	2.7	0	0
Constipation	10	13.7	2	2.7	0	0	0	0
Liver dysfunction	6	8.2	0	0	0	0	0	0
Mucositis oral	2	2.7	2	2.7	1	1.4	0	0
Abdominal pain	8	11.0	2	2.7	0	0	0	0
Fever	3	4.1	0	0	0	0	0	0
Anorexia	22	30.1	2	2.7	0	0	0	0
Hand-foot syndrome	1	1.4	2	2.7	0	0
Myalgia and arthralgia	5	6.8	1	1.4	0	0	0	0
Skin hyperpigmentation	9	12.3	5	6.8	0	0	0	0
Blurred vision	2	2.7	2	2.7	0	0	0	0
Nail change	5	6.8	3	4.1	0	0	0	0
Insomnia	4	5.5	0	0	0	0	0	0
Hearing impaired	0	0	1	1.4	0	0	0	0
Edema	2	2.7	0	0	0	0	0	0
Dysphasia	1	1.4	0	0	0	0	0	0
Watering eyes	1	1.4	1	1.4	0	0	0	0
Dizziness	2	2.7	0	0	0	0	0	0
Dyspnea	1	1.4	0	0	0	0	0	0

Table 5 Taxane-containing regimens for metastatic breast cancer

Study	Regimen	Study design and setting	Number of patients	Overall response rate	Median time to progression/progression-free survival (months)	Median overall survival (months)
Our study	Nab-paclitaxel 125 mg/m^2, days 1, 8, 15 + DDP 75 mg/m^2, q4w	Phase II, all lines	73	67.1%	9.8	26.9
Our study	Investigator assessment	First-line	36	80.6%	11.7	NR
(first-line)	Independent assessment	First-line	36	77.8%	11.7
O’shaughnessy et al^Citation26	Capecitabine 1,250 mg/m^2 twice daily on days 1 to 14 + docetaxel 75 mg/m^2 day 1, q3w	Phase III, all lines	255	42%	6.1	14.5
Albain et al^Citation27	Gemcitabine 1,250 mg/m^2 days 1, 8 + paclitaxel 175 mg/m^2 day 1, q3w	Phase III, first-line	266	41.4%	6.1	18.6
Miller et al^Citation28	Paclitaxel 90 mg/m^2 days 1, 8, 15 + bevacizumab 10 mg/kg days 1 and 15, q4w	Phase III, first-line	347	36.9%	11.8	26.7
Miles et al^Citation29	Docetaxel 100 mg/m^2 + bevacizumab 15 mg/kg day 1, q3w	Phase III, first-line	247	63%	10.1	30.3
Slamon et al^Citation30	Chemotherapy plus heceptin	Phase III, first-line	235	50%	7.4	25.1
Wardley et al^Citation31	Heceptin (8 mg/kg loading; 6 mg/kg q3w) + docetaxel (75 mg/m^2 q3w) + xeloda (950 mg/m^2 twice daily on days 1 to 14 q3w)	Phase II, first-line	113	70.5%	18.6	NR

Abbreviations: q3w, every 3 weeks; q4w, every 4 weeks; NR, not reached.

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