155P Prolonged clinical benefit with metronomic chemotherapy (VEX regimen) in metastatic breast cancer patients

1054 Background: Resistance mechanisms to CDK 4/6 inhibition are not well defined. Outcome data on hormone receptor positive (HR+) metastatic breast cancer patients (MBCP) treated with palbociclib (PA) after treatment with everolimus (EV) are lacking. The PALOMA 3 trial (P3) showing benefit of PA plus fulvestrant (FU) compared to FU in HR+ MBCP after progression on endocrine therapy excluded women previously treated with EV. The aim of our study was to investigate the outcomes of HR+ MBCP with prior EV treatment on PA based therapy. Methods: This is a retrospective, single institute review of HR+, HER 2 nonamplified MBCP from Jan 2014 - Nov 2016 treated with PA after treatment with EV. Women who received EV for < 1 month or PA < 14 days were excluded. Progression free survival (PFS) was defined as the time from the initiation of PA to the date of progression as determined by treating physician based on radiological, biochemical and/or clinical criteria. Response rates were determined based on available radiological data. Clinical benefit was defined as a complete response (CR), partial response (PR) or stable disease of at least 24 weeks. Results: 23 patients with mean age 67 years (42 to 81) were identified. 95% were postmenopausal, 81% had ECOG performance status 0 or 1, 83% had visceral metastases, 95% had > 2 lines of prior endocrine therapy (ET), 82% shown prior sensitivity to ET, 82% received prior chemotherapy, of which 84% were in metastatic setting. Kaplan Meier estimate showed median PFS of 2.9 months (95% CI 2.0-4.2); median PFS of P3 PA cohort was 9.5 months (95% CI 9.2-11.0). Fisher’s exact test comparing study cohort with P3 PA cohort showed statistically significant differences in objective response (CR or PR) rates of 0/23 (0%) vs. 66/347 (19%, p = 0.02) & clinical benefit ratio of 4/23 (17.4%) vs. 231/347 (66.5%, p = 0.00). Conclusions: Outcomes with PA in HR+ EV treated MBCP were worse when compared to the P3 PA cohort data. Treatment with EV may lead to resistance to CDK inhibition. Though limited by size, our data suggests that use of PA after EV is associated with low response & clinical benefit rates. Further studies are necessary to confirm the findings to determine sequencing of targeted therapies.

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Frequency ofPIK3CAMutations in Chinese HER2+ Metastatic Breast Cancer Patients and Association with Clinical Benefit to Lapatinib and Capecitabine Treatment.

10.1158/0008-5472.sabcs-09-1140 ◽

2009 ◽

Author(s):

B. Xu ◽

J. Zefei ◽

D. Chua ◽

Z. Shao ◽

R. Luo ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Clinical Benefit ◽

Metastatic Breast ◽

Breast Cancer Patients

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Serum EGFR and serum HER-2/neu are useful predictive and prognostic markers in metastatic breast cancer patients treated with metronomic chemotherapy

Cancer ◽

10.1002/cncr.22825 ◽

2007 ◽

Vol 110 (3) ◽

pp. 509-517 ◽

Cited By ~ 27

Author(s):

Maria Teresa Sandri ◽

Harriet Ann Johansson ◽

Laura Zorzino ◽

Michela Salvatici ◽

Rita Passerini ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Prognostic Markers ◽

Metastatic Breast ◽

Metronomic Chemotherapy ◽

Breast Cancer Patients ◽

Her 2

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Phase II Trial of Veliparib and Temozolomide in Metastatic Breast Cancer Patients With and Without BRCA1/2mutations

10.21203/rs.3.rs-268461/v1 ◽

2021 ◽

Author(s):

Jing Xu ◽

Tanya E Keenan ◽

Beth Overmoyer ◽

Nadine Muskatel Tung ◽

Rebecca Gelman ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Phase Ii ◽

Clinical Benefit ◽

Phase Ii Trial ◽

Brca Mutation ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Expansion Cohort

Abstract Purpose: We evaluated the efficacy and safety of poly-(adenosine diphosphate-ribose) polymerase (PARP) 1 and 2 inhibitor veliparib and temozolomide in metastatic breast cancer patients with and without germline BRCA1/2 mutations.Methods: In this single-arm phase II trial, patients with metastatic breast cancer received veliparib 30 to 40 mg twice daily on days 1 to 7 with concurrent temozolomide 150 mg/m2 on days 1 to 5 of a 28-day cycle. The primary cohort was unselected for BRCA mutation status, and an expansion cohort enrolled only BRCA1/2 carriers. The primary endpoint was objective response rate (ORR) in each cohort. Secondary endpoints included progression free survival (PFS), clinical benefit rate (CBR), and evaluation of safety and tolerability.Results: In the primary cohort of 41 unselected patients, which included 9 BRCA mutation carriers, the ORR was 10% and clinical benefit rate at 4 months (CBR) was 27%. In the expansion cohort of 21 BRCA1/2 carriers, the ORR was 14% and CBR was 43%. Among all 30 BRCA1/2 carriers, the ORR was 23% versus 0% among non-carriers. In the subset of BRCA1/2 carriers, the ORR was 32% among platinum-naïve patients versus 9% among platinum-exposed patients. The median PFS was 3.3 months among BRCA1/2 carriers compared to 1.8 months among non-carriers (HR: 0.48, p = 0.006). A longer median PFS of 6.2 months was observed among BRCA1/2 carriers who had no prior platinum therapy. The most common grade 3 and 4 toxicities were thrombocytopenia (32%) and neutropenia (21%) that generally improved with dose modifications.Conclusion: Veliparib and temozolomide demonstrated clinical activity in platinum-naïve BRCA-associated metastatic breast cancer with manageable toxicity at doses of veliparib well below the single agent active dose. Although the study did not meet its primary endpoint in unselected nor BRCA-associated breast cancer, this regimen was further evaluated in the BROCADE 2 study. Trial registration: NCT01009788 (ClinicalTrials.gov), November 9, 2009

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Maintenance metronomic chemotherapy combined with conventional treatment for metastatic breast cancer patients

Annals of Oncology ◽

10.1093/annonc/mdw365.24 ◽

2016 ◽

Vol 27 ◽

pp. vi75 ◽

Cited By ~ 1

Author(s):

S.F. El Zawawy ◽

G. Khedr ◽

B. Elsabaa

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Conventional Treatment ◽

Metastatic Breast ◽

Metronomic Chemotherapy ◽

Breast Cancer Patients

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LOW-DOSE METRONOMIC CHEMOTHERAPY WITH CYCLOPHOSPHAMIDE AND METHOTREXATE IN METASTATIC BREAST CANCER PATIENTS

10.26226/morressier.599bdc7bd462b80296ca08cf ◽

2017 ◽

Author(s):

Slavomir Krajnak

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Low Dose ◽

Metastatic Breast ◽

Metronomic Chemotherapy ◽

Breast Cancer Patients

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Efficacy and Safety of Vinorelbine-Capecitabine Oral Metronomic Combination in Elderly Metastatic Breast Cancer Patients: VICTOR-1 Study

Tumori Journal ◽

10.5301/tj.5000543 ◽

2017 ◽

Vol 103 (1) ◽

pp. e4-e8 ◽

Cited By ~ 8

Author(s):

Marina E. Cazzaniga ◽

Valter Torri ◽

Francesca Riva ◽

Luca Porcu ◽

Federica Cicchiello ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Clinical Benefit ◽

Objective Response ◽

Metastatic Breast ◽

Efficacy And Safety ◽

Breast Cancer Patients ◽

Oral Vinorelbine ◽

Metastatic Sites

Purpose Elderly patients with metastatic breast cancer are expected to derive similar benefits from chemotherapy as younger patients, but are more likely to experience therapy-related toxicity. Data from the VICTOR-1 study showed that metronomic therapy with vinorelbine and capecitabine was effective and well tolerated in patients with metastatic breast cancer. This analysis determined the efficacy and safety of the metronomic combination of oral vinorelbine and capecitabine in a subgroup of VICTOR-1 study patients aged ≥70 years. Methods Eighteen of the 32 patients enrolled in VICTOR-1 were aged ≥70 years. Objective response and clinical benefit rates were calculated and toxicity was determined using the NCI-CTCAE criteria. Results All patients had at least 1 comorbidity (4 had 2 comorbidities), and 77.7% were taking concomitant medication. Eight patients (44%) had received ≥1 chemotherapy regimens for metastatic disease and most (78%) had ≥2 metastatic sites. Grade 1-2 adverse events occurred in 45.8% of cycles, whereas the incidence of grade 3 and grade 4 events was very low (1.5% and 0.7%, respectively). Median time to progression was 10.5 months (range 1-40). The objective response rate was 33% and the clinical benefit rate was 67%. Conclusions The all-oral metronomic combination of vinorelbine and capecitabine had an acceptable efficacy profile and appears to be better tolerated than standard treatment schedules in elderly metastatic breast cancer patients (age ≥70 years).

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