Overall Survival in Metastatic Breast Cancer Patients in the Third Millennium: Results of the COSMO Study

none18Metastatic breast cancer (MBC) is a life-threatening disease, and although some data suggest a trend in survival improvement, it has not yet been unequivocally demonstrated. This study aimed to evaluate the overall survival (OS) of MBC patients, assessing its correlation with prognostic factors.openLa Verde, Nicla; Collovà, Elena; Blasi, Livio; Pinotti, Graziella; Palumbo, Raffaella; Bonotto, Marta; Garrone, Ornella; Brunello, Antonella; Rimanti, Anita; Bareggi, Claudia; Zaniboni, Alberto; Frassoldati, Antonio; Foglietta, Jennifer; Berardi, Rossana; Moretti, Anna; Farina, Gabriella; Porcu, Luca; Barni, SandroLa Verde, Nicla; Collovà, Elena; Blasi, Livio; Pinotti, Graziella; Palumbo, Raffaella; Bonotto, Marta; Garrone, Ornella; Brunello, Antonella; Rimanti, Anita; Bareggi, Claudia; Zaniboni, Alberto; Frassoldati, Antonio; Foglietta, Jennifer; Berardi, Rossana; Moretti, Anna; Farina, Gabriella; Porcu, Luca; Barni, Sandr

Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer: ERIGE trial on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC).

Background: There are no well-established chemotherapy regimens for metastatic triple negative breast cancer. The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, especially in tumors like triple negative breast cancers (TNBC) characterized by high cell proliferation, aggressive tumor behavior, and chemo-resistance. Methods: We performed an open-label, national multicenter phase 2 study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on day 1 and 8, q21 as either first- or second-line treatment of locally advanced or metastatic TNBC. The Simon's optimal two-stage design was used for estimating objective response rate (ORR) as study primary endpoint. A prospective, molecular correlative study was carried out on germinal DNA of study population to assess the role of germinal DNA polymorphisms and BRCA mutations in predicting efficacy and toxicity of the combination regimen. Results: From July 2013 to September 2016, 83 (37 in the first stage, 46 in the second one) assessable patients were enrolled. Median age at baseline was 56 years. Sixty-six and 17 patients were in first or second-line treatment, respectively. All patients were previously treated with an anthracycline and/or a taxane. With regard to the first stage of study enrolment, patients received a median number of 6 cycles of treatment. The ORR (CR+PR) was 43.24% (90% CI 29.3-58.0) and the clinical benefit rate (CR+PR+SD) was 64.9% (90% CI: 50.1%-77.8%). The most common grade 3/4 AEs ( > 10% of patients) were neutropenia without febrile neutropenia and liver toxicity. Grade 1/2 AEs were fatigue, anemia, thrombocytopenia, diarrhea, alopecia, peripheral neuropathy, and oral mucositis. Conclusions: The combination of eribulin and gemcitabine shows promising activity and a moderate toxicity profile in metastatic TNBC. More mature toxicity and outcome data of the final study population and correlation with genome analysis will be presented at the meeting. Clinical trial information: 2012-003505-10

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Association among gene polymorphisms and risk of toxicity of any grade (grade1–2–3-4 vs 0). (DOC 83 kb

Efficacy of trastuzumab in unselected patients with HER2-positive metastatic breast cancer: A retrospective analysis

AIMS AND BACKGROUND: The addition of trastuzumab to chemotherapy for HER2-positive metastatic breast cancer has significantly improved progression-free survival and overall survival, although most patients develop resistance or have a primarily resistant disease. The aim of the study was to describe the efficacy and safety of a first-line treatment in unselected metastatic HER2-positive breast cancer patients, treated according to clinical practice. METHODS: From 2000 to 2009, we conducted a retrospective multi-institutional analysis of 182 consecutive patients with HER2-positive metastatic breast cancer who underwent first-line treatment with trastuzumab. The primary end points were progression-free survival and overall survival; the secondary end points were survival after progression in patients treated with second-line chemotherapy with or without trastuzumab and safety. A total of 172 patients were analyzed. RESULTS: Median progression-free survival and overall survival were 1.2 (95% CI, 1.1-1.4) and 4.4 years (95% CI, 3.6-5.4), respectively. For 100 patients who received second-line chemotherapy, median survival after progression was significantly longer in those who also received trastuzumab: 2.8 (95% CI, 2.1-4.0) versus 1.2 years (95% CI, 0.6-1.9). CONCLUSIONS: Although based on retrospective data, the study confirms the role of trastuzumab as first-line treatment in metastatic breast cancer outside of a controlled trial. Moreover, information obtained on the use of trastuzumab beyond disease progression supports its use in this settin

Predictive Factors of Lapatinib and Capecitabine Activity in Patients with HER2-Positive, Trastuzumab-Resistant Metastatic Breast Cancer: Results from the Italian Retrospective Multicenter HERLAPAC Study.

BACKGROUND:There are no validated predictive markers for lapatinib and capecitabine in patients with trastuzumab-resistant HER2 positive metastatic breast cancer. METHODS:Data of 148 consecutive patients treated with lapatinib and capecitabine from March 2007 to December 2013 were collected from 13 Italian institutions. Estimates of progression-free survival (PFS) and overall survival (OS) were obtained with the Kaplan-Meier method and compared with logrank test. The association of clinicopathological variables and the outcome was studied by binary logistic regression analysis and Cox proportional hazard analysis. RESULTS:At a median follow-up of 41 months, median PFS and OS were 7 and 21 months, respectively. Patents with a PFS longer than 7 months had a significantly longer OS, compared with patients with a PFS equal to or shorter than 7 months (36 vs 15 months; p<0.001). Multivariate analysis revealed the benefit of lapatinib-based therapy in terms of PFS and OS was significantly associated with time-to-progression (TTP) on prior first-line trastuzumab-based therapy. In particular, each additional month on first-line trastuzumab based therapy was associated with a reduction in hazard of progression and death after the initiation of lapatinib-based therapy of 2% and 4%, respectively. CONCLUSIONS:A longer TTP to first line trastuzumab seems to predict a prolonged PFS and OS with subsequent lapatinib and capecitabine