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Review
. 2022 Aug:64:7-18.
doi: 10.1016/j.breast.2022.04.006. Epub 2022 Apr 15.

Moment of truth-adding carboplatin to neoadjuvant/adjuvant chemotherapy in triple negative breast cancer improves overall survival: An individual participant data and trial-level Meta-analysis

Neha Pathak  1 , Aparna Sharma  2 , Arunmozhimaran Elavarasi  3 , Jeeva Sankar  4 , S V S Deo  5 , Daya N Sharma  6 , Sandeep Mathur  7 , Sudhir Kumar  8 , Chandra P Prasad  9 , Akash Kumar  10 , Atul Batra  11
Affiliations
Review

Moment of truth-adding carboplatin to neoadjuvant/adjuvant chemotherapy in triple negative breast cancer improves overall survival: An individual participant data and trial-level Meta-analysis

Neha Pathak et al. Breast. 2022 Aug.

Abstract

Importance: Carboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial.

Methods: The study was prospectively registered at PROSPERO (CRD42021228386). We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes.

Results: Eight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I2 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I2 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44-3.08; I2 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm.

Conclusion: and relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis.

Keywords: Adjuvant; Carboplatin; Chemotherapy; Neoadjuvant; Platinum; TNBC; Triple negative breast cancer.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
PRISMA diagram of search results and study selection.
Fig. 2
Fig. 2
a and b Risk of bias assessment.
Fig. 3
Fig. 3
a (random effects model) and b (fixed effects model).
Fig. 4
Fig. 4
a: Forest plot of DFS subgroup: studies with ddCT in the control arm and b: Forest plot of DFS subgroup: studies non-ddCT in the control arm.
Fig. 4
Fig. 4
a: Forest plot of DFS subgroup: studies with ddCT in the control arm and b: Forest plot of DFS subgroup: studies non-ddCT in the control arm.
Fig. 5
Fig. 5
Funnel plot for DFS.
Fig. 6
Fig. 6
Kaplan Meier graph of DFS and OS of carboplatin vs AT (SOC), IPD analysis.
Fig. 7
Fig. 7
(a) Forest plot for pooled OS for carboplatin vs SOC(random-effects model) and (b) Forest plot for pooled OS for carboplatin vs SOC(fixed-effects model).
Fig. 7
Fig. 7
(a) Forest plot for pooled OS for carboplatin vs SOC(random-effects model) and (b) Forest plot for pooled OS for carboplatin vs SOC(fixed-effects model).
Fig. 8
Fig. 8
(a) Forest plot of OS subgroup ddCT as the control arm and (b) Forest plot of OS subgroup non-ddCT as the control arm.
Fig. 8
Fig. 8
(a) Forest plot of OS subgroup ddCT as the control arm and (b) Forest plot of OS subgroup non-ddCT as the control arm.
Fig. 9
Fig. 9
Forest plot for pCR for Carboplatin vs SOC in NACT.
Fig. 10
Fig. 10
Forest plot of pCR excluding ddCT studies.
Fig. 11
Fig. 11
Forest plot of Adverse events of carboplatin vs SOC** Indicate adjuvant chemotherapy studies; rest are neoadjuvant studies.
See this image and copyright information in PMC

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