Abstract P4-06-01: Platinum-based chemotherapy for early triple-negative breast cancer: A Cochrane systematic review and meta-analysis
Authors: Mason Sofia , Willson Melina , Goodwin Annabel , Beith Jane , Egger Sam J. , Dear Rachel F. 
Published: March 2023

Abstract
In early triple-negative breast cancer (eTNBC), platinum-based chemotherapy has been shown to improve pathological complete response, but recommendations to include platinum chemotherapy are not consistent in international guidelines. We performed a systematic review of published randomized control trials to assess to assess survival outcomes and quality of life for people with early TNBC. The results presented in this abstract have not yet been peer-reviewed by Cochrane. If the final version of the review meets the necessary standards, the review is expected to be published in the Cochrane Database of Systematic Reviews. Methods: Randomized controlled trials examining neoadjuvant or adjuvant platinum chemotherapy for eTNBC were included. We searched for published and unpublished data using standard Cochrane search strategies. The primary outcomes assessed were disease free survival (DFS) and overall survival (OS). Secondary outcomes included rate of pathological complete response (pCR), dose intensity and completion of regimens, grade III or IV toxicity related to chemotherapy, and quality of life. Prespecified subgroups included BRCA mutation status, HRD status, lymph node status, frequency of chemotherapy, type of platinum agent used, and the presence or absence of anthracycline chemotherapy. Results: From 3972 records, 19 published studies were eligible. Twenty six ongoing studies were identified. Risk of bias was judged low for most trials. There were 14 neoadjuvant chemotherapy trials, 4 adjuvant chemotherapy trials, and one trial of neoadjuvant and adjuvant therapy. Most trials used carboplatin (16 trials) followed by cisplatin (2), and lobaplatin (1). Eight trials had an anthracycline free intervention arm, 5 of which had a carboplatin-taxane intervention compared to an anthracycline-taxane control. All studies reporting DFS and OS used carboplatin. Twelve of 19 studies with a total of 3347 participants reported DFS data. Inclusion of platinum chemotherapy improved DFS in neoadjuvant and adjuvant setting (HR 0.63, 95% confidence interval (CI) 0.53-0.75; HR 0.69, 95% CI 0.54-0.88 respectively)). Eleven studies collected OS data, with a total of 3229 participants and 460 deaths reported. Inclusion of platinum chemotherapy in the regimen improved OS (neoadjuvant: HR 0.69, 95% CI 0.69, 0.55-0.86; adjuvant: 0.70, 95% CI 0.50 to 0.96). Median follow up for survival outcomes ranged from 36 – 97.6 months. Our analysis confirmed platinum chemotherapy increased pCR rates (RR 1.46 [1.33-1.61], p&lt; 0.00001). Subgroup analysis revealed that survival outcome benefits were seen regardless of BRCA mutation status, HRD status, lymph node status, or whether the intervention arm contained anthracycline chemotherapy or not. Platinum chemotherapy was associated with reduced dose intensity, with participants more likely to require chemotherapy delays (RR 2.23 [1.70-2.94], 4 studies), dose reductions (RR 1.77 [1.56-2.02], 6 studies) and early cessation of treatment (RR 1.20 [1.04-1.38], 16 studies). Increased hematological toxicity occurred in the platinum group who were more likely to experience grade III/IV neutropenia (RR 1.55 [1.45-1.66]), anemia (RR 10.12 [6.61-15.50]) and thrombocytopenia (RR 7.59 [5.10-11.29]). There was no increase in febrile neutropenia (RR 1.16 [0.89-1.49]). Treatment-related death was very rare (7 events in 3094 patients) and similar across treatment groups (RR 0.58 [0.14-2.33]). Five studies collected quality of life data but did not report it. Conclusion: Platinum-based chemotherapy using carboplatin in the adjuvant or neoadjuvant setting improves long-term outcomes in eTNBC, regardless of the examined subgroups. This was at the cost of more frequent chemotherapy delays and dose reductions, and greater haematological toxicity. Benefit from platinum was seen both when platinum agents were added to anthracycline containing regimens, as well as in anthracycline-free regimens.
Citation Format: Sofia Mason, Melina Willson, Annabel Goodwin, Jane Beith, Sam J. Egger, Rachel F. Dear. Platinum-based chemotherapy for early triple-negative breast cancer: A Cochrane systematic review and meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-01.