Abstract PS11-30: Can metronomic maintenance therapy (MMT) after completion of standard therapy help prevent relapses in patients (Pts) with non-metastatic triple-negative breast cancer (TNBC)
Authors: Bajaj Kripa , Banavali Shripad 
Published: February 2021

Abstract
Background: In-spite of the standard neoadjuvant and adjuvant therapies, stage for stage many more patients with TNBC relapse. This may be because of lack of effective maintenance therapy for TNBC Pts. Recently MMT is being explored to improve outcomes in TNBC. We present a retrospective and prospective analysis of consecutive Pts with TNBC treated at BKLWalawalkarHospital, the rural outreach center of Tata Memorial Centre (India), wherein the outcome of TNBC Pts receiving MMT is being compared to historical control group who did not receive the same.
Methods: After standard anthracycline or anthracycline+taxane based therapy, TNBC Pts were either observed (Sept 2003 to March 2011) or received MMT (Nov 2008 to Dec 2018).MMT consisted of 2 phases: initial 12 weeks of daily oral celecoxib (200 mg BD) and cyclophosphamide (50 mg OD) along with 12 doses of weekly IV cisplatin (25 mg/m2). This was followed by 1 year of Phase II maintenance consisting of oral daily metformin (500 mg BD), cyclophosphamide (50 mg OD) along with weekly methotrexate (12 mg/m2).When CAF is the standard regimen 2 phases of maintenance was given , after anthracyclines and taxanes were proved as a standard regimen maintenance was restricted to Phase II considering overlapping toxicities like neuropathy.
Results: There were 118 evaluable TNBC Pts. 25 Pts did not receive any MMT.Of the 93 remaining Pts initial 25 received both Phase I & II MMT , 1 patient received only phase I and subsequent 61 Pts have received only Phase II MMT. 6 patients progressed while on initial standard therapy and were not evaluable to assess the effect of MMT .Hence 112 patients are analysed further for outcome.STAGE STRATIFICATION : 8 Pts(6.7%) had AJCC Stage I; 48 Pts(40.6%) had AJCC Stage II; & 62 patients(52.5) had AJCC Stage III disease.MMT and observation groups were comparable with respect to baseline characteristics such as age & stage . Out of 112 patients 87 received MMT and 9 events were noted ,25 did not received MMT and 12 events were noted.EFS by March 2020 is 89.7% in MMT group and 52% in non- MMT group . Median EFS in MMT group is 11.3 yrs ( 9.4 yrs-13.14 yrs 95% CI) , in Off MMT group median EFS 9.2 yrs( 6.4-12 yrs 95% CI).Overall comparison was done by Log rank analysis (Significance 0.006).Median overall survival in OMCT group is 11.8yrs ( 9.9yrs-13.8yrs 95% CI), in non MMT group OS is 9.8yrs( 7.1 yrs-12.6yrs) with significance 0.002.61 patients who received Phase II MMT OS is 13.4 yrs ( 12.5yrs-14.4 yrs 95% CI).By stage stratification in non MMT group 2 patients belong to Stage I , 9patients belongs to Stage II and 14 patients belongs to Stage III.
TOXICITIES : MTX 25% dose reduction was done in 7 patients due to Grd2 Mucositis, cyclophosphamide alone was stopped in 1 patient due to grade 3 fatigue, MTX and Cyclophosphamide was stopped in 2 patientsdue grade3 anemia and grade 4 neutropenia, blood transfusion was done in them.Toxicities are much less when compared to CREATEX trial and the follow up duration is very long.
Conclusion: Most of the TNBC patients relapse in the early period of follow up and there is an unmet need in the improvement of management. If low dose chemotherapy is given for 1 yr there is a significant improvement in EFS and OS without muchdecrease in QOL.l. This strategy is worthy of being evaluated in definitive randomized trials in TNBC women with large numbers.
Citation Format: Kripa Bajaj, Shripad Banavali. Can metronomic maintenance therapy (MMT) after completion of standard therapy help prevent relapses in patients (Pts) with non-metastatic triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-30.