Platinum‐containing regimens for metastatic breast cancer

Sam J Egger; Melina L Willson; Jenna Morgan; Harriet S Walker; Sue Carrick; Davina Ghersi; Nicholas Wilcken

doi:10.1002/14651858.CD003374.pub4

Scolaris Content Display Scolaris Content Display

Contenido relacionado

Ir a:

Revisiones y protocolos relacionados
Respuestas clínicas Cochrane
Guías
Temas

Revisiones y protocolos relacionados

Respuestas clínicas Cochrane

Topics

Temas

Figure 1

Review update 2016: study flow diagram.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Funnel plot 1: Overall survival (OS). Assessing publication bias and/or small‐study effects. Plot includes all treatment‐comparisons with extractable data for OS. The plot does not show asymmetry (Egger's test P value = 0.98)

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 4

Forest plot of comparison: 1 Platinum vs non‐platinum regimens (subgroup analysis 1: by treatment‐comparisons assessing mTNBC), outcome: 1.1 Overall survival.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 5

Forest plot of comparison: 1 Platinum vs non‐platinum regimens (subgroup analysis 1: by treatment‐comparisons assessing mTNBC), outcome: 1.2 Progression‐free survival/time to progression.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 6

Forest plot of comparison: 1 Platinum vs non‐platinum regimens (subgroup analysis 1: by treatment‐comparisons assessing mTNBC), outcome: 1.3 Objective tumour response rate (assessable participants).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1 Platinum vs non‐platinum regimens (subgroup analysis 1: by treatment‐comparisons assessing mTNBC), Outcome 1 Overall survival.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1 Platinum vs non‐platinum regimens (subgroup analysis 1: by treatment‐comparisons assessing mTNBC), Outcome 2 Progression‐free survival/time to progression.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1 Platinum vs non‐platinum regimens (subgroup analysis 1: by treatment‐comparisons assessing mTNBC), Outcome 3 Objective tumour response rate (assessable participants).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.1

Comparison 2 Platinum vs non‐platinum regimens (subgroup analysis 2: by type of regimen comparison), Outcome 1 Overall survival.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.2

Comparison 2 Platinum vs non‐platinum regimens (subgroup analysis 2: by type of regimen comparison), Outcome 2 Progression‐free survival / time to progression.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.3

Comparison 2 Platinum vs non‐platinum regimens (subgroup analysis 2: by type of regimen comparison), Outcome 3 Objective tumour response rate (assessable participants).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.1

Comparison 3 Platinum vs non‐platinum regimens (subgroup analysis 3: by type of platinum agent in platinum arm), Outcome 1 Overall survival.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.2

Comparison 3 Platinum vs non‐platinum regimens (subgroup analysis 3: by type of platinum agent in platinum arm), Outcome 2 Progression‐free survival/time to progression.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.3

Comparison 3 Platinum vs non‐platinum regimens (subgroup analysis 3: by type of platinum agent in platinum arm), Outcome 3 Objective tumour response rate (assessable participants).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.4

Comparison 3 Platinum vs non‐platinum regimens (subgroup analysis 3: by type of platinum agent in platinum arm), Outcome 4 Treatment‐related death (safety population).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.5

Comparison 3 Platinum vs non‐platinum regimens (subgroup analysis 3: by type of platinum agent in platinum arm), Outcome 5 Nausea/vomiting (safety population).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.6

Comparison 3 Platinum vs non‐platinum regimens (subgroup analysis 3: by type of platinum agent in platinum arm), Outcome 6 Nephrotoxicity (safety population).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.7

Comparison 3 Platinum vs non‐platinum regimens (subgroup analysis 3: by type of platinum agent in platinum arm), Outcome 7 Anaemia (safety population).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.8

Comparison 3 Platinum vs non‐platinum regimens (subgroup analysis 3: by type of platinum agent in platinum arm), Outcome 8 Hair loss (safety population).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.9

Comparison 3 Platinum vs non‐platinum regimens (subgroup analysis 3: by type of platinum agent in platinum arm), Outcome 9 Leukopenia (safety population).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 4.1

Comparison 4 Platinum vs non‐platinum regimens (subgroup analysis 4: by first‐line therapy), Outcome 1 Overall survival.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 4.2

Comparison 4 Platinum vs non‐platinum regimens (subgroup analysis 4: by first‐line therapy), Outcome 2 Progression‐free survival/time to progression.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 4.3

Comparison 4 Platinum vs non‐platinum regimens (subgroup analysis 4: by first‐line therapy), Outcome 3 Objective tumour response rate (assessable participants).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 5.1

Comparison 5 Platinum vs non‐platinum regimens (subgroup analysis 5 by anthracycline in regimens), Outcome 1 Overall survival.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 5.2

Comparison 5 Platinum vs non‐platinum regimens (subgroup analysis 5 by anthracycline in regimens), Outcome 2 Progression‐free survival/time to progression.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 5.3

Comparison 5 Platinum vs non‐platinum regimens (subgroup analysis 5 by anthracycline in regimens), Outcome 3 Objective tumour response rate (assessable participants).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 6.1

Comparison 6 Platinum vs non‐platinum regimens (subgroup analysis 6: by taxane in regimens), Outcome 1 Overall survival.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 6.2

Comparison 6 Platinum vs non‐platinum regimens (subgroup analysis 6: by taxane in regimens), Outcome 2 Progression‐free survival / time to progression.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 6.3

Comparison 6 Platinum vs non‐platinum regimens (subgroup analysis 6: by taxane in regimens), Outcome 3 Objective tumour response rate (assessable participants).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 7.1

Comparison 7 Platinum vs non‐platinum regimens (subgroup analysis 7: by trastuzumab in regimens), Outcome 1 Overall survival.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 7.2

Comparison 7 Platinum vs non‐platinum regimens (subgroup analysis 7: by trastuzumab in regimens), Outcome 2 Progression‐free survival/time to progression.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 7.3

Comparison 7 Platinum vs non‐platinum regimens (subgroup analysis 7: by trastuzumab in regimens), Outcome 3 Objective tumour response rate (assessable participants).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.1

Comparison 8 Platinum vs non‐platinum regimens (sensitivity analysis 1: excluding selected treatment‐comparisons), Outcome 1 Overall survival (restricted to the 12 treatment‐comparisons common to OS and PFS/TTP meta‐analyses).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.2

Comparison 8 Platinum vs non‐platinum regimens (sensitivity analysis 1: excluding selected treatment‐comparisons), Outcome 2 Progression‐free survival/time to progression (restricted to the 12 treatment‐comparisons common to OS and PFS/TTP meta‐analyses).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.3

Comparison 8 Platinum vs non‐platinum regimens (sensitivity analysis 1: excluding selected treatment‐comparisons), Outcome 3 Objective tumour response rate (assessable participants‐ restricted to the 19 treatment‐comparisons in OS meta‐analyses).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.1

Comparison 9 Platinum vs non‐platinum regimens (sensitivity analysis 2: Progression‐free survival vs. time to progression), Outcome 1 Progression‐free survival vs time to progression.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 10.1

Comparison 10 Platinum vs non‐platinum regimens (sensitivity analysis 3: Analyses 1 repeated but with random effects approach), Outcome 1 Overall survival.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 10.2

Comparison 10 Platinum vs non‐platinum regimens (sensitivity analysis 3: Analyses 1 repeated but with random effects approach), Outcome 2 Progression‐free survival/time to progression.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 10.3

Comparison 10 Platinum vs non‐platinum regimens (sensitivity analysis 3: Analyses 1 repeated but with random effects approach), Outcome 3 Objective tumour response rate (assessable participants).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings for the main comparison. Platinum‐containing regimens for women with metastatic breast cancer unselected for triple‐negative disease

Platinum compared to non‐platinum chemotherapy regimens for women with metastatic breast cancer unselected for triple‐negative disease
Patient or population: women with metastatic breast cancer unselected for triple‐negative breast cancer (TNBC) Setting: hospital Intervention: platinum Comparison: non‐platinum chemotherapy regimens
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	No. of participants (treatment‐ comparisons)	Quality of the evidence (GRADE)	Comments
	Risk with non‐platinum chemotherapy regimens	Risk with platinum
Overall survival ‐ trials of metastatic breast cancer participants unselected for TNBC	1‐year risk of death		HR 1.01 (0.92 to 1.12)	2531 (16)	⊕⊕⊕⊕ HIGH³	Heterogeneity: P = 0.09, I²=34%
	310 per 1,000 ¹	313 per 1,000 (289 to 340)²
	2‐year risk of death
	540 per 1,000 ¹	543 per 1,000 (510 to 581)²
Progression‐free survival/time to progression (randomised participants) ‐ trials of metastatic breast cancer participants unselected for TNBC	1‐year risk of progression or death		HR 0.92 (0.84 to 1.01)	1745 (13)	⊕⊕⊕⊝ MODERATE⁴	Heterogeneity: P = 0.08, I²=38%
	737 per 1,000 ¹	707 per 1,000 (674 to 740)²
	2‐year risk of progression or death
	891 per 1,000 ¹	869 per 1,000 (844 to 893)²
Objective tumour response rate (assessable participants) ‐ trials of metastatic breast cancer participants unselected for TNBC	493 per 1,000 ⁵	547 per 1,000 (512 to 586)	RR 1.11 (1.04 to 1.19)	3252 (23)	⊕⊕⊝⊝ LOW^4,6	Heterogeneity: P = 0.0002, I²=58%
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; HR: Hazard ratio;
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ Estimated from the average of non‐platinum group Kaplan‐Meier probabilities from the three highest weighted non‐TNBC treatment‐comparisons for this outcome ² Estimated as 1000*(1‐S(t)^HR) where S(t) is the estimated probability of survival for non‐platinum participants and HR is the pooled hazard ratio (Davies 1998) ³ Quality of evidence for OS was not downgraded for blinding because this outcome is unlikely to be affected by non‐blinding. ⁴ Downgraded quality of evidence one level for 'indirectness' because this outcome is a surrogate endpoint of questionable validity for assessing the more important outcome of OS in the context of metastatic breast cancer (Burzykowski 2008) ⁵ Estimated from all 23 non‐TNBC treatment‐comparisons in the review ⁶ Downgraded quality of evidence one level for 'inconsistency' because there was substantial evidence of heterogeneity across studies (P < 0.05)

Summary of findings for the main comparison. Platinum‐containing regimens for women with metastatic breast cancer unselected for triple‐negative disease

Ir a la tabla de la revisión

Summary of findings 2. Platinum‐containing regimens for women with metastatic triple‐negative breast cancer

Platinum compared to non‐platinum chemotherapy regimens for women with metastatic triple‐negative breast cancer
Patient or population: women with metastatic triple‐negative breast cancer (mTNBC) Setting: hospital Intervention: platinum Comparison: non‐platinum chemotherapy regimens
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	No. of participants (treatment‐ comparisons)	Quality of the evidence (GRADE)	Comments
	Risk with non‐platinum chemotherapy regimens	Risk with platinum
Overall survival ‐ trials of mTNBC participants	1‐year risk of death		HR 0.75 (0.57 to 1.00)	391 (3)	⊕⊕⊝⊝ LOW^3,4,5	Heterogeneity: P = 0.23, I² = 32%
	485 per 1,000 ¹	392 per 1,000 (315 to 485)²
	2‐year risk of death
	655 per 1,000 ¹	550 per 1,000 (455 to 655)²
Progression‐free survival/time to progression (randomised participants) ‐ trials of mTNBC participants	1‐year risk of death		HR 0.59 (0.49 to 0.72)	391 (3)	⊕⊕⊝⊝ LOW^4,6	Heterogeneity: P = 0.07, I² = 67%
	894 per 1,000 ¹	733 per 1,000 (667 to 801)²
	2‐year risk of death
	987 per 1,000 ¹	922 per 1,000 (879 to 955)²
Objective tumour response rate (assessable participants) ‐ trials of mTNBC participants	354 per 1,000⁷	470 per 1,000 (400 to 552)	RR 1.33 (1.13 to 1.56)	878 (5)	⊕⊕⊝⊝ LOW^6,8	Heterogeneity: P = 0.0010, I² = 78%
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; HR: Hazard ratio;
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ Estimated from the average of non‐platinum group Kaplan‐Meier probabilities from the three TNBC treatment‐comparisons contributing data for pooling on this outcome ² Estimated as 1000*(1‐S(t)^HR) where S(t) is the estimated probability of survival for non‐platinum participants and HR is the pooled hazard ratio (Davies 1998) ³ Downgraded quality of evidence one level for 'imprecision' because the confidence interval for the pooled estimate is wide and crosses or nearly crosses unity ⁴ Downgraded quality of evidence one level for 'suspected publication bias' because Tutt 2014 is a large study with 376 participants but has so far only reported median OS/PFS times. As a consequence, the study did not contribute to the pooled HR estimates for OS or PFS/TTP. The reported median OS/PFS times in Tutt 2014 were similar between platinum and non‐platinum regimens. Hence, it seems likely that if HRs from Tutt 2014 were able to be included in pooled HR estimates, these pooled estimates would be considerably closer to the null. ⁵ Quality of evidence for OS was not downgraded for blinding because this outcome is unlikely to be affected by non‐blinding. ⁶ Downgraded quality of evidence one level for 'indirectness' because this outcome is a surrogate endpoint of questionable validity for assessing the more important outcome of OS in the context of metastatic breast cancer (Burzykowski 2008) ⁷Estimated from all five TNBC treatment‐comparisons in the review ⁸ Downgraded quality of evidence one level for 'inconsistency' because there was substantial evidence of heterogeneity across studies (P < 0.05)

Summary of findings 2. Platinum‐containing regimens for women with metastatic triple‐negative breast cancer

Ir a la tabla de la revisión

Summary of findings 3. Platinum‐containing regimens and toxicity profile

Platinum compared to non‐platinum chemotherapy regimens for nausea/vomiting, anaemia, hair loss and leukopenia
Patient or population: women with metastatic breast cancer Setting: hospital Intervention: platinum Comparison: non‐platinum chemotherapy regimens
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	No. of participants (treatment‐ comparisons)	Quality of the evidence (GRADE)	Comments
	Risk with non‐platinum chemotherapy regimens	Risk with platinum
Nausea/vomiting* grade 3 or 4 (safety population) by type of platinum agent in platinum regimen	Carboplatin		(RR 0.77, 95% CI 0.47 to 1.26)	1441 (7)	⊕⊕⊕⊝ MODERATE²	Test for carboplatin/cisplatin subgroup difference: P < 0.0001 Heterogeneity among carboplatin studies: P = 0.30, I² = 17% Heterogeneity among cisplatin studies: P = 0.010, I² = 32%
	80 per 1,000 ¹	62 per 1,000 (59 to 101)
	Cisplatin		(RR 2.65, 95% CI 2.10 to 3.34)	1747 (14)	⊕⊕⊕⊝ MODERATE³
	80 per 1,000 ¹	210 per 1,000 (167 to 266)
Anaemia grade 3 or 4 (safety population) by type of platinum agent in platinum regimen	Carboplatin		(RR 1.72, 95% CI 1.10 to 2.70)	1441 (7)	⊕⊕⊕⊕ HIGH	Test for carboplatin/cisplatin subgroup difference: P = 0.02 Heterogeneity among carboplatin studies: P = 0.67, I² = 0% Heterogeneity among cisplatin studies: P = 0.50, I² = 0%
	33 per 1,000 ¹	57 per 1,000 (36 to 89)
	Cisplatin		(RR 3.72, 95% CI 2.36 to 5.88)	1644 (13)	⊕⊕⊕⊕ HIGH
	33 per 1,000 ¹	123 per 1,000 (78 to 194)
Hair loss grade 3 or 4 (safety population)	Carboplatin or cisplatin		(RR 1.41, 95% CI 1.26 to 1.58)	1452 (13)	⊕⊕⊕⊕ HIGH	Test for carboplatin/cisplatin subgroup difference: P = 0.23 Heterogeneity: P = 0.10, I² = 40%
	264 per 1,000 ¹	372 per 1,000 (333 to 417)
Leukopenia** grade 3 or 4 (safety population)	Carboplatin or cisplatin		(RR 1.38, 95% CI 1.21 to 1.57)	3176 (22)	⊕⊕⊕⊝ MODERATE³	Test for carboplatin/cisplatin subgroup difference: P = 0.22 Heterogeneity: P = 0.0002, I² = 60%
	179 per 1,000 ¹	247 per 1,000 (217 to 281)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; HR: Hazard ratio;
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ Estimated from all treatment‐comparisons (cisplatin and carboplatin) contributing data for pooling for this outcome ² Downgraded quality of evidence one level for 'imprecision' because the confidence interval for the pooled estimate is wide and does not rule out 'no effect' ³ Downgraded quality of evidence one level for 'inconsistency' because there was substantial evidence of heterogeneity across studies (P < 0.05) data on vomiting was included if data on nausea/vomiting was reported separately *data on neutropenia was included if data on leukopenia was not reported

Summary of findings 3. Platinum‐containing regimens and toxicity profile

Ir a la tabla de la revisión

Table 1. Platinum agents

Generic name	Other names
Carboplatin	Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, Nealorin, Novoplatinum, Paraplat, Paraplatin AQ, Paraplatin, Paraplatine, Platinwas, Ribocarbo
Cisplatin	Abiplatin, Blastolem, Briplatin,CACP, CDDP, cis‐DDP, cis‐diamminedichloridoplatinum, cis‐diamminedichloro platinum (II), cis‐diamminedichloroplatinum, Cis‐dichloroammine Platinum (II), Cismaplat, Cisplatina, cis‐platinous diamine dichloride, cis‐platinum II diamine dichloride, cis‐platinum II, cis‐platinum, Cisplatyl, Citoplatino, Citosin, CPDD, Cysplatyna, DDP, DDP, Lederplatin, Metaplatin, Neoplatin, PDD, Peyrone's Chloride, Peyrone's Salt, Placis, Platamine, Platiblastin, Platiblastin‐S, Platinex, Platinol‐ AQ, Platinol, Platinol‐AQ VHA Plus, Platinol‐AQ, Platinoxan, platinum diamminodichloride, Platiran, Platistin, Platosin
Oxaliplatin	Ai Heng, Aiheng, diaminocyclohexane oxalatoplatinum, oxalatoplatin, oxalatoplatinum, oxaliplatine, Eloxatin, Dacotin, Dacplat, Eloxatine, 1‐OHP, L‐OHP, oxaliplatin medac

Table 1. Platinum agents

Ir a la tabla de la revisión

Table 2. Chemotherapeutic Agents (adapted from Table 1.1 in The Chemotherapy Source Book)

Type of Agent	Action	Includes
Agents that damage the DNA template	by alkylation: nitrogen mustards	cyclophosphamide, melphalan, ifosfamide, chlorambucil
	by alkylation: nitrosureas	carmustine (BCNU), lomustine (CCNU)
	by alkylation: other agents	thiotepa, mitomycin C
	by platinum coordination cross‐linking	cisplatin, carboplatin
	antibiotics	doxorubicin, daunorubicin, mitoxantrone, idarubicin, epirubicin, amsacrine
	podophyllotoxins	etoposide, teniposide
	by intercalation	dactinomycin, mithramycin
	by uncertain mechanisms	bleomycin
Spindle poisons	vinca alkaloids	vincristine, vinblastine, vendesine, vinorelbine
	taxanes	taxol, taxotere
Antimetabolites	thymidylate synthase	5‐fluorouracil
	dihydrofolate reductase	methotrexate

Table 2. Chemotherapeutic Agents (adapted from Table 1.1 in The Chemotherapy Source Book)

Ir a la tabla de la revisión

Table 3. Number of treatment‐comparisons included in meta‐analyses by subgroup and three outcomes

		Outcome
Subgroup	Treatment‐ comparisons N	Overall survival n (% of N)	Progression ‐free survival/time to progression n (% of N)	Objective response rate n (% of N)
Overall:	28	19 (68%)	16 (57%)	28 (100%)
Type of platinum agent in platinum arm:
Cisplatin in platinum arm	17	11 (65%)	11 (65%)	17 (100%)
Carboplatin in platinum arm	10	8 (80%)	5 (50%)	10 (100%)
Oxaliplatin in platinum arm	1	(0%)	(0%)	1 (100%)
Type of regimen comparison:
Regimen A + platinum agent vs regimen A	9	6 (67%)	6 (67%)	9 (100%)
Regimen A + platinum agent vs regimen B	18	13 (72%)	10 (56%)	18 (100%)
Single agent platinum vs regimen C	1	(0%)	(0%)	1 (100%)
First‐line therapy:
First‐line therapy for > 80% of participants	20	15 (75%)	11 (55%)	20 (100%)
Second‐ or third‐line therapy for ≥ 20% of participants	8	4 (50%)	5 (63%)	8 (100%)
Participant selection for mTNBC:
Participants with mTNBC	5	3 (60%)	3 (60%)	5 (100%)
Participants unselected for mTNBC	23	16 (70%)	13 (57%)	23 (100%)
Anthracycline in regimens:
No anthracycline in platinum or non‐platinum regimens	18	14 (78%)	11 (61%)	18 (100%)
Platinum + anthracycline vs non‐platinum + anthracycline regimens	6	3 (50%)	4 (67%)	6 (100%)
Platinum + anthracycline vs non‐platinum + non‐anthracycline regimens	4	2 (50%)	1 (25%)	4 (100%)
Taxane in regimens:
No taxane in platinum or non‐platinum regimens	17	9 (53%)	9 (53%)	17 (100%)
Platinum + taxane vs non‐platinum + taxane regimens	6	6 (100%)	3 (50%)	6 (100%)
Platinum + non‐taxane vs non‐platinum + taxane regimens	5	4 (80%)	4 (80%)	5 (100%)
Trastuzumab in regimens:
No trastuzumab in platinum or non‐platinum regimens	26	17 (65%)	14 (54%)	26 (100%)
Platinum + trastuzumab vs non‐platinum + trastuzumab regimens	2	2 (100%)	2 (100%)	2 (100%)

Table 3. Number of treatment‐comparisons included in meta‐analyses by subgroup and three outcomes

Ir a la tabla de la revisión

Table 4. Summary of regimens included in the analysis

Trials ID	Arm 1 (platinum‐containing)	Arm 2 (control)	First‐line therapy for > 80% of participants	Majority participants anthracycline‐naive
Regimen A + platinum vs regimen A
Berruti 2002 A	Epi + Cis (epirubicin+cisplatin)	Epi (epirubicin)	Y	Y
Berruti 2002 B	Epi + Cis + LND (epirubicin+cisplatin+lonidamine)	Epi + LND (epirubicin + lonidamine)	Y	Y
Bhattacharyya 2009	Endoxan 50 mg per day at 10 am and methotrexate 2.5 mg twice a day at 9 am and 5 pm and with 'cisplatinum'	Endoxan 50 mg per day at 10 am and methotrexate 2.5 mg twice a day at 9 am and 5 pm	N	N
Carey 2012	C + Cb (Cetuximab + carboplatin)	C (Cetuximab with carboplatin added after progression)	N	N
Costanza 1999	CBDA + CAF (carboplatin + cycloheximide + doxorubicin + fluorouracil + methotrexate)	CAF (cycloheximide + doxorubicin + fluorouracil) (methotrexate substituted after total doxorubicin ‐ 540 mg)	Y	Unclear
Fountzilas 2009 A	PCb (paclitaxel + carboplatin)	Pw (paclitaxel)	Y	N
Nielsen 2000	Epi + Cis (epirubicin + cisplatin)	Epi (epirubicin)	Y	Y
Robert 2006	TPC (trastuzumab + paclitaxel + carboplatin)	TP (trastuzumab + paclitaxel)	Y	Unclear
Valero 2011	TCH (trastuzumab + docetaxel + carboplatin)	TH (trastuzumab + docetaxel)	Y	N
Regimen A + platinum vs regimen B
Amadori 2013	(pemetrexed + carboplatin)	(vinorelbine + gemcitabine)	N	N
Cocconi 1991	MPEPIV(a) or MPEMi (b) (a: methotrexate, leucovorin, cisplatin, epirubicin, vincristine; b: methotrexate, leucovorin, cisplatin, etoposide, mitomycin)	CMF (cyclophosphamide, methotrexate, fluorouracil)	Y	Y
Cocconi 1996	Etop + Cis (etoposide + cisplatin)	CMF (cyclophosphamide, methotrexate, fluorouracil)	Y	Unclear
Cocconi 1999	PE + CMF + AL (cisplatin + etoposide + doxorubicin + cyclophosphamide, methotrexate + fluorouracil, lecovorin + allopurinol)	CMF (cyclophosphamide, methotrexate, fluorouracil)	Y	Unclear
Creagan 1984	CFP + CAP (cyclophosphamide + doxorubicin + cis‐dichlordiammine + CFP)	CFP (cyclophosphamide + fluorouracil + prednisone)	Y	Y
Delaloge 2004	OXA (oxaliplatin + 5‐flurouracil)	VIN (vinorelbine)	N	N
Eisen 1998	EcisF (5‐flurouracil + epirubicin + cisplatin)	EcycloF (5‐flurouracil + epirubicin + cyclophosphamide)	Y	Y
Fan 2012	TP (docetaxel + cisplatin)	TX (docetaxel + capecitabine)	Y	N
Fountzilas 2004	Epi + Pcb (epirubicin + carboplatin)	Epi + P (epirubicin + paclitaxel)	Y	Y (54%)
Fountzilas 2009 B	PCb (paclitaxel + carboplatin)	GDoc (docetaxel + gemcitabine)	Y	N
Hu 2015	(cisplatin + gemcitabine)	(paclitaxel + gemcitabine)	Y	N
Icli 2005	Etop + Cis (etoposide + cisplatin)	P (paclitaxel)	N	N
Kolaric 1985	CAP (cyclophosphamide + doxorubicin + platinum)	CMFVP (cyclophosphamide + methotrexate + 5‐fluorouracil + vincristine + prednisone)	Y	Y
Kolaric 1989	CAP (cyclophosphamide + doxorubicin +platinum)	FAC (5‐flurouracil + doxorubicin + cyclophosphamide)	Y	Y
Stemmler 2011 A	GemCis (gemcitabine + cisplatin)	GemVin (gemcitabine + vinorelbine)	N	N
Stemmler 2011 B	GemCis (gemcitabine + cisplatin)	GemCap (gemcitabine + capecitabine)	N	N
Xu 2011 A	GemCis (gemcitabine + cisplatin)	GemPac (gemcitabine + paclitaxel)	Y	N
Xu 2011 B	GemCarb (gemcitabine + carboplatin)	GemPac (gemcitabine + paclitaxel)	Y	N
Single agent platinum vs regimen C
Tutt 2014	C (carboplatin)	D (docetaxel)	N	Unclear

Table 4. Summary of regimens included in the analysis

Ir a la tabla de la revisión

Table 5. Summary of outcomes for included trials

Trial ID	Extractable OS data for HR estimation¹	Median OS time²	Extractable PFS/TTP data for HR estimation¹	Median PFS/TTP time²	Overall response	Treatment‐related deaths	Grade III & IV Toxicity	Accrual³
Regimen A + platinum vs regimen A
Berruti 2002 A	NR	Y	Y	Y	Y	Y	Nausea/vomiting Nephrotoxicity Anaemia Leukopenia	185
Berruti 2002 B	NR	Y	Y	Y	Y	Y	Nausea/vomiting Nephrotoxicity Anaemia Leukopenia	186
Bhattacharyya 2009	NR	Y	NR	Y	Y	NR	NR	126
Carey 2012	Y	Y	Y	NR	Y	NR	Not extractable	102
Costanza 1999	Y	Y	NR	NR	Y	Y	Nausea/vomiting Anaemia Leukopenia	221
Fountzilas 2009 A	Y	Y	NR	NR	Y	Y	Nausea/vomiting Anaemia Hair loss Leukopenia	204
Nielsen 2000	Y	Y	Y	Y	Y	Y	Nausea/vomiting Leukopenia	155
Robert 2006	Y	Y	Y	Y	Y	NR	Nausea/vomiting Anaemia Leukopenia	196
Valero 2011	Y	Y	Y	Y	Y	Y	Nausea/vomiting Anaemia	263
Regimen A + platinum vs regimen B
Amadori 2013	NR	NR	Y	Y	Y	Y	Leukopenia	135
Cocconi 1991	Y	Y	NR	Y	Y	NR	Anaemia Leukopenia	140
Cocconi 1999	Y	Y	NR	Y	Y	NR	Nausea/vomiting Anaemia Hair loss Leukopenia	105
Cocconi 1996	NR	Y	NR	Y	Y	DU	Not extractable	169
Creagan 1984	Y	Y	Y	Y	Y	NR	Nausea/vomiting Hair loss Leukopenia	86
Delaloge 2004	NR	Y	NR	Y	Y	Y	Not extractable	137
Eisen 1998	NR	Y	Y	Y	Y	DU	Nausea/vomiting Anaemia Hair loss Leukopenia	59
Fan 2012	Y	Y	Y	Y	Y	Y	Nausea/vomiting Anaemia Leukopenia	53
Fountzilas 2004	Y	NR	NR	NR	Y	NR	Nausea/vomiting Anaemia Leukopenia	327
Fountzilas 2009 B	Y	Y	NR	NR	Y	Y	Nausea/vomiting Anaemia Hair loss Leukopenia	212
Hu 2015	Y	NR	Y	Y	Y	Y	Nausea/vomiting Anaemia Hair loss Leukopenia	236
Icli 2005	Y	Y	Y	NR	Y	Y	Nausea/vomiting Anaemia Leukopenia	193
Kolaric 1985	NR	NR	NR	NR	Y	NR	Nausea/vomiting Nephrotoxicity Anaemia Hair loss Leukopenia	123
Kolaric 1989	Y	Y	NR	NR	Y	Y	Nausea/vomiting Anaemia Hair loss Leukopenia	142
Stemmler 2011 A	Y	Y	Y	Y	Y	NR	Nausea/vomiting Anaemia Hair loss Leukopenia	69
Stemmler 2011 B	Y	Y	Y	Y	Y	NR	Nausea/vomiting Anaemia Hair loss Leukopenia	72
Xu 2011 A	Y	Y	Y	Y	Y	Y	Nausea/vomiting Nephrotoxicity Anaemia Hair loss Leukopenia	75
Xu 2011 B	Y	Y	Y	Y	Y	Y	Nausea/vomiting Nephrotoxicity Anaemia Hair loss Leukopenia	71
Single agent platinum vs regimen C
Tutt 2014	NR	Y	NR	Y	Y	NR	NR	376
¹ Sufficient data reported to estimate a HR for pooling as outlined by Parmar 1998 and Tierney 2007; this includes Kapalan‐Meier curve, HR and standard error/confidence interval or logrank statistics ² Trials that did not explicitly report median time were classified as NR here regardless of estimable median time from Kaplan‐Meier curve ³ Accrual numbers represent the maximum numbers of participants in the trial (not study) that were included in the analyses of OS, PFS/TTP or OR (assessable participants). *NR = not reported, DU = deaths unexplained, Y = data reported.

Table 5. Summary of outcomes for included trials

Ir a la tabla de la revisión

Comparison 1. Platinum vs non‐platinum regimens (subgroup analysis 1: by treatment‐comparisons assessing mTNBC)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival Show forest plot	19	2922	HR (95% CI)	0.98 [0.89, 1.07]

1.1 Treatment‐comparisons assessing patients with mTNBC	3	391	HR (95% CI)	0.75 [0.57, 1.00]
1.2 Treatment‐comparisons assessing patients unselected for mTNBC	16	2531	HR (95% CI)	1.01 [0.92, 1.12]
2 Progression‐free survival/time to progression Show forest plot	16	2136	HR (95% CI)	0.85 [0.78, 0.93]

2.1 Treatment‐comparisons assessing patients with mTNBC	3	391	HR (95% CI)	0.59 [0.49, 0.72]
2.2 Treatment‐comparisons assessing patients unselected for mTNBC	13	1745	HR (95% CI)	0.92 [0.84, 1.01]
3 Objective tumour response rate (assessable participants) Show forest plot	28	4130	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [1.08, 1.22]

3.1 Treatment‐comparisons assessing patients with mTNBC	5	878	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [1.13, 1.56]
3.2 Treatment‐comparisons assessing patients unselected for mTNBC	23	3252	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [1.04, 1.19]

Comparison 1. Platinum vs non‐platinum regimens (subgroup analysis 1: by treatment‐comparisons assessing mTNBC)

Ir a la tabla de la revisión

Comparison 2. Platinum vs non‐platinum regimens (subgroup analysis 2: by type of regimen comparison)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival Show forest plot	19	2922	HR (95% CI)	0.98 [0.89, 1.07]

1.1 Regimen A + platinum agent vs regimen A	6	1141	HR (95% CI)	1.08 [0.93, 1.26]
1.2 Regimen A + platinum agent vs regimen B	13	1781	HR (95% CI)	0.92 [0.81, 1.03]
2 Progression‐free survival / time to progression Show forest plot	16	2136	HR (95% CI)	0.85 [0.78, 0.93]

2.1 Regimen A+platinum agent vs regimen A	6	1087	HR (95% CI)	0.88 [0.78, 1.00]
2.2 Regimen A+platinum agent vs regimen B	10	1049	HR (95% CI)	0.83 [0.74, 0.93]
3 Objective tumour response rate (assessable participants) Show forest plot	28	4130	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [1.08, 1.22]

3.1 Regimen A + platinum agent vs regimen A	9	1519	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [1.01, 1.21]
3.2 Regimen A + platinum agent vs regimen B	18	2235	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [1.12, 1.33]
3.3 Single agent platinum vs regimen C	1	376	Risk Ratio (M‐H, Fixed, 95% CI)	0.88 [0.66, 1.17]

Comparison 2. Platinum vs non‐platinum regimens (subgroup analysis 2: by type of regimen comparison)

Ir a la tabla de la revisión

Comparison 3. Platinum vs non‐platinum regimens (subgroup analysis 3: by type of platinum agent in platinum arm)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival Show forest plot	19	2922	HR (95% CI)	0.98 [0.89, 1.07]

1.1 Cisplatin in platinum arm	11	1326	HR (95% CI)	0.91 [0.80, 1.05]
1.2 Carboplatin in platinum arm	8	1596	HR (95% CI)	1.04 [0.91, 1.18]
2 Progression‐free survival/time to progression Show forest plot	16	2136	HR (95% CI)	0.85 [0.78, 0.93]

2.1 Cisplatin in platinum arm	11	1369	HR (95% CI)	0.85 [0.76, 0.94]
2.2 Carboplatin in platinum arm	5	767	HR (95% CI)	0.86 [0.75, 0.99]
3 Objective tumour response rate (assessable participants) Show forest plot	28	4130	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [1.08, 1.22]

3.1 Cisplatin in platinum arm	17	2050	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [1.24, 1.46]
3.2 Carboplatin in platinum arm	10	1943	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.86, 1.04]
3.3 Oxaliplatin in platinum arm	1	137	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.48, 1.52]
4 Treatment‐related death (safety population) Show forest plot	15	2377	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [0.73, 2.76]

4.1 Cisplatin in platinum arm	8	1185	Risk Ratio (M‐H, Fixed, 95% CI)	1.39 [0.59, 3.25]
4.2 Carboplatin in platinum arm	6	1055	Risk Ratio (M‐H, Fixed, 95% CI)	1.86 [0.57, 6.05]
4.3 Oxaliplatin in platinum arm	1	137	Risk Ratio (M‐H, Fixed, 95% CI)	0.34 [0.01, 8.16]
5 Nausea/vomiting (safety population) Show forest plot	21	3172	Risk Ratio (M‐H, Fixed, 95% CI)	2.07 [1.69, 2.54]

5.1 Cisplatin in platinum arm	14	1731	Risk Ratio (M‐H, Fixed, 95% CI)	2.65 [2.10, 3.34]
5.2 Carboplatin in platinum arm	7	1441	Risk Ratio (M‐H, Fixed, 95% CI)	0.77 [0.47, 1.26]
6 Nephrotoxicity (safety population) Show forest plot	5	632	Risk Ratio (M‐H, Fixed, 95% CI)	3.06 [0.86, 10.84]

6.1 Cisplatin in platinum arm	4	561	Risk Ratio (M‐H, Fixed, 95% CI)	3.46 [0.86, 13.97]
6.2 Carboplatin in platinum arm	1	71	Risk Ratio (M‐H, Fixed, 95% CI)	1.56 [0.07, 36.97]
7 Anaemia (safety population) Show forest plot	20	3085	Risk Ratio (M‐H, Fixed, 95% CI)	2.61 [1.90, 3.58]

7.1 Cisplatin in platinum arm	13	1644	Risk Ratio (M‐H, Fixed, 95% CI)	3.72 [2.36, 5.88]
7.2 Carboplatin in platinum arm	7	1441	Risk Ratio (M‐H, Fixed, 95% CI)	1.72 [1.10, 2.70]
8 Hair loss (safety population) Show forest plot	12	1452	Risk Ratio (M‐H, Fixed, 95% CI)	1.41 [1.26, 1.58]

8.1 Cisplatin in platinum arm	9	983	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [1.15, 1.54]
8.2 Carboplatin in platinum arm	3	469	Risk Ratio (M‐H, Fixed, 95% CI)	1.53 [1.28, 1.84]
9 Leukopenia (safety population) Show forest plot	22	3176	Risk Ratio (M‐H, Fixed, 95% CI)	1.38 [1.21, 1.57]

9.1 Cisplatin in platinum arm	15	1866	Risk Ratio (M‐H, Fixed, 95% CI)	1.49 [1.23, 1.81]
9.2 Carboplatin in platinum arm	7	1310	Risk Ratio (M‐H, Fixed, 95% CI)	1.27 [1.07, 1.50]

Comparison 3. Platinum vs non‐platinum regimens (subgroup analysis 3: by type of platinum agent in platinum arm)

Ir a la tabla de la revisión

Comparison 4. Platinum vs non‐platinum regimens (subgroup analysis 4: by first‐line therapy)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival Show forest plot	19	2922	HR (95% CI)	0.98 [0.89, 1.07]

1.1 First‐line therapy for > 80% of patients	15	2486	HR (95% CI)	1.00 [0.90, 1.11]
1.2 Second‐ or third‐line therapy for ≥20% of patients	4	436	HR (95% CI)	0.89 [0.73, 1.09]
2 Progression‐free survival/time to progression Show forest plot	16	2136	HR (95% CI)	0.85 [0.78, 0.93]

2.1 First‐line therapy for > 80% of patients	11	1565	HR (95% CI)	0.93 [0.83, 1.03]
2.2 Second‐ or third‐line therapy for ≥20% of patients	5	571	HR (95% CI)	0.75 [0.65, 0.86]
3 Objective tumour response rate (assessable participants) Show forest plot	28	4130	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [1.08, 1.22]

3.1 First‐line therapy for > 80% of patients	20	2983	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [1.06, 1.21]
3.2 Second‐ or third‐line therapy for ≥20% of patients	8	1147	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [1.02, 1.42]

Comparison 4. Platinum vs non‐platinum regimens (subgroup analysis 4: by first‐line therapy)

Ir a la tabla de la revisión

Comparison 5. Platinum vs non‐platinum regimens (subgroup analysis 5 by anthracycline in regimens)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival Show forest plot	19	2922	HR (95% CI)	0.98 [0.89, 1.07]

1.1 No anthracycline in platinum or non‐platinum regimens	14	2213	HR (95% CI)	0.94 [0.84, 1.05]
1.2 Platinum + anthracycline vs non‐platinum + anthracycline regimens	3	518	HR (95% CI)	1.09 [0.88, 1.34]
1.3 Platinum + anthracycline vs non‐platinum + non‐anthracycline regimens	2	191	HR (95% CI)	1.12 [0.78, 1.60]
2 Progression‐free survival/time to progression Show forest plot	16	2136	HR (95% CI)	0.85 [0.78, 0.93]

2.1 No anthracycline in platinum or non‐platinum regimens	11	1465	HR (95% CI)	0.80 [0.73, 0.88]
2.2 Platinum+anthracycline vs non‐platinum+anthracycline regimens	4	585	HR (95% CI)	1.05 [0.86, 1.27]
2.3 Platinum+anthracycline vs non‐platinum+non‐anthracycline regimens	1	86	HR (95% CI)	1.23 [0.75, 2.03]
3 Objective tumour response rate (assessable participants) Show forest plot	28	4130	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [1.08, 1.22]

3.1 No anthracycline in platinum or non‐platinum regimens	18	2792	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [1.02, 1.20]
3.2 Platinum+anthracycline vs non‐platinum+anthracycline regimens	6	859	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.97, 1.22]
3.3 Platinum+anthracycline vs non‐platinum+non‐anthracycline regimens	4	479	Risk Ratio (M‐H, Fixed, 95% CI)	1.49 [1.28, 1.74]

Comparison 5. Platinum vs non‐platinum regimens (subgroup analysis 5 by anthracycline in regimens)

Ir a la tabla de la revisión

Comparison 6. Platinum vs non‐platinum regimens (subgroup analysis 6: by taxane in regimens)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival Show forest plot	19	2922	HR (95% CI)	0.98 [0.89, 1.07]

1.1 No taxane in platinum or non‐platinum regimens	9	1092	HR (95% CI)	1.07 [0.93, 1.24]
1.2 Platinum + taxane vs non‐platinum + taxane regimens	6	1255	HR (95% CI)	0.96 [0.82, 1.11]
1.3 Platinum + non‐taxane vs non‐platinum + taxane regimens	4	575	HR (95% CI)	0.85 [0.69, 1.04]
2 Progression‐free survival / time to progression Show forest plot	16	2136	HR (95% CI)	0.85 [0.78, 0.93]

2.1 No taxane in platinum or non‐platinum regimens	9	1049	HR (95% CI)	0.92 [0.80, 1.04]
2.2 Platinum + taxane vs non‐platinum + taxane regimens	3	512	HR (95% CI)	0.84 [0.70, 1.00]
2.3 Platinum + non‐taxane vs non‐platinum + taxane regimens	4	575	HR (95% CI)	0.79 [0.69, 0.91]
3 Objective tumour response rate (assessable participants) Show forest plot	28	4130	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [1.08, 1.22]

3.1 No taxane in platinum or non‐platinum regimens	17	2054	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [1.15, 1.36]
3.2 Platinum + taxane vs non‐platinum + taxane regimens	6	1152	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.90, 1.12]
3.3 Platinum + non‐taxane vs non‐platinum + taxane regimens	5	924	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.94, 1.30]

Comparison 6. Platinum vs non‐platinum regimens (subgroup analysis 6: by taxane in regimens)

Ir a la tabla de la revisión

Comparison 7. Platinum vs non‐platinum regimens (subgroup analysis 7: by trastuzumab in regimens)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival Show forest plot	19	2922	HR (95% CI)	0.98 [0.89, 1.07]

1.1 No trastuzumab in platinum or non‐platinum regimens	17	2463	HR (95% CI)	0.97 [0.88, 1.08]
1.2 Platinum + trastuzumab vs non‐platinum + trastuzumab regimens	2	459	HR (95% CI)	1.00 [0.79, 1.27]
2 Progression‐free survival/time to progression Show forest plot	16	2136	HR (95% CI)	0.85 [0.78, 0.93]

2.1 No trastuzumab in platinum or non‐platinum regimens	14	1677	HR (95% CI)	0.84 [0.76, 0.92]
2.2 Platinum+trastuzumab vs non‐platinum+trastuzumab regimens	2	459	HR (95% CI)	0.90 [0.75, 1.08]
3 Objective tumour response rate (assessable participants) Show forest plot	28	4130	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [1.08, 1.22]

3.1 No trastuzumab in platinum or non‐platinum regimens	26	3687	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [1.07, 1.23]
3.2 Platinum+trastuzumab vs non‐platinum+trastuzumab regimens	2	443	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.99, 1.31]

Comparison 7. Platinum vs non‐platinum regimens (subgroup analysis 7: by trastuzumab in regimens)

Ir a la tabla de la revisión

Comparison 8. Platinum vs non‐platinum regimens (sensitivity analysis 1: excluding selected treatment‐comparisons)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival (restricted to the 12 treatment‐comparisons common to OS and PFS/TTP meta‐analyses) Show forest plot	12	1571	HR (95% CI)	0.92 [0.81, 1.04]

2 Progression‐free survival/time to progression (restricted to the 12 treatment‐comparisons common to OS and PFS/TTP meta‐analyses) Show forest plot	12	1571	HR (95% CI)	0.80 [0.73, 0.88]

3 Objective tumour response rate (assessable participants‐ restricted to the 19 treatment‐comparisons in OS meta‐analyses) Show forest plot	19	2685	Risk Ratio (M‐H, Fixed, 95% CI)	1.13 [1.05, 1.22]

Comparison 8. Platinum vs non‐platinum regimens (sensitivity analysis 1: excluding selected treatment‐comparisons)

Ir a la tabla de la revisión

Comparison 9. Platinum vs non‐platinum regimens (sensitivity analysis 2: Progression‐free survival vs. time to progression)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Progression‐free survival vs time to progression Show forest plot	16	2136	HR (95% CI)	0.85 [0.78, 0.93]

1.1 Progression‐free survival	9	1324	HR (95% CI)	0.92 [0.82, 1.03]
1.2 Time to progression	7	812	HR (95% CI)	0.78 [0.69, 0.88]

Comparison 9. Platinum vs non‐platinum regimens (sensitivity analysis 2: Progression‐free survival vs. time to progression)

Ir a la tabla de la revisión

Comparison 10. Platinum vs non‐platinum regimens (sensitivity analysis 3: Analyses 1 repeated but with random effects approach)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival Show forest plot	19		Hazard Ratio (Random, 95% CI)	0.98 [0.87, 1.11]

1.1 Treatment‐comparisons assessing patients with mTNBC	3		Hazard Ratio (Random, 95% CI)	0.73 [0.51, 1.04]
1.2 Treatment‐comparisons assessing patients unselected for mTNBC	16		Hazard Ratio (Random, 95% CI)	1.02 [0.90, 1.16]
2 Progression‐free survival/time to progression Show forest plot	16		Hazard Ratio (Random, 95% CI)	0.88 [0.76, 1.02]

2.1 Treatment‐comparisons assessing patients with mTNBC	3		Hazard Ratio (Random, 95% CI)	0.55 [0.38, 0.78]
2.2 Treatment‐comparisons assessing patients unselected for mTNBC	13		Hazard Ratio (Random, 95% CI)	0.96 [0.85, 1.09]
3 Objective tumour response rate (assessable participants) Show forest plot	28	4130	Risk Ratio (M‐H, Random, 95% CI)	1.17 [1.05, 1.30]

3.1 Treatment‐comparisons assessing patients with mTNBC	5	878	Risk Ratio (M‐H, Random, 95% CI)	1.60 [1.04, 2.45]
3.2 Treatment‐comparisons assessing patients unselected for mTNBC	23	3252	Risk Ratio (M‐H, Random, 95% CI)	1.13 [1.01, 1.25]

Comparison 10. Platinum vs non‐platinum regimens (sensitivity analysis 3: Analyses 1 repeated but with random effects approach)

Ir a la tabla de la revisión

The Cochrane Library

Scolaris Language Selector Scolaris Language Selector

Idioma de la Revisión Cochrane

Idioma de la web

Scolaris Content Language Banner Portlet Scolaris Content Language Banner Portlet

Scolaris Content Display Scolaris Content Display

Temas

Scolaris Language Selector Scolaris Language Selector

Scolaris Content Display Scolaris Content Display

Instituciones a las que se accedió previamente

Scolaris Content Display Scolaris Content Display

Usuarios institucionales

Instituciones a las que se accedió previamente

Otras opciones de acceso

	Idioma de la Revisión Cochrane Escoja su idioma de preferencia para las revisiones Cochrane y otros contenidos. Las secciones sin una traducción aparecerán en inglés.

	Idioma de la web Escoja su idioma de preferencia para la web de la Biblioteca Cochrane.

Idioma de la Revisión Cochrane

Idioma de la web

Contenido relacionado

Revisiones y protocolos relacionados

Respuestas clínicas Cochrane

Temas

Copiar o descargar referencia

Idioma de la Revisión Cochrane

Idioma de la web

Instituciones a las que se accedió previamente

Usuarios institucionales

Instituciones a las que se accedió previamente

Otras opciones de acceso