Evaluation at 3 years of concurrent bevacizumab and radiotherapy for breast cancer: Results of a prospective study.

PURPOSE: To determine the 3 years late toxicity among patients with non-metastatic breast cancer who received concurrent bevacizumab and locoregional radiotherapy. MATERIAL AND METHODS: This is a single-arm, multicentre, prospective study, of the toxicity of adjuvant concomitant association of bevacizumab and radiotherapy in patients with breast cancer. Toxicity was assessed by the Common Terminology Criteria for Adverse Events version 3.0 during the radiotherapy and follow-up clinics at 12 and 36 months after its completion. The study was designed to evaluate the toxicity at one year, 3 years and 5 years. RESULTS: Sixty-four patients were included from October 2007 to August 2010. All of them received concurrent adjuvant radiotherapy and bevacizumab (in 24 cases after primary systemic treatment). All patients received non-fractionated radiotherapy to breast or chest wall with or without irradiation of regional lymph nodes. Early toxicity has been previously reported. Median follow-up was 46.4 months (range: 18-77 months). Median age was 53 years old (range: 23-68 years). The 3-years overall survival was 93% (range: 87-100%). Evaluation of the toxicity at 3 years was available for 67% of the patients. There was a low rate of toxicity: 14% grade 1 pain, 9% grade 1 fibrosis, 2% grade 1 telangiectasia, 2% grade 1 paresis, 7% grade 1 lymphedema and 2% grade 3 lymphedema. No grade 4 toxicity was observed. No patient had a left ventricular ejection fraction below 50% at 3 years. CONCLUSIONS: Concurrent bevacizumab with locoregional radiotherapy is associated with acceptable 3-years toxicity in patients with breast cancer.

Late toxicities and outcomes of adjuvant radiotherapy combined with concurrent bevacizumab in patients with triple-negative non-metastatic breast cancer.

OBJECTIVE: To evaluate the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (B-RT) in breast cancer (BC). METHODS: Multicentre, prospective study, of the toxicity of adjuvant radiotherapy (RT) alone or B-RT in patients with non-metastatic BC enrolled in randomized Phase 3 BEATRICE trial. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events v. 3.0 during and 12 months after the completion of RT. RESULTS: From 2007 to 2012, 39 females received adjuvant B-RT and 45 received adjuvant RT alone. Median follow-up was 21.5 months. All patients had triple-negative non-metastatic BC and received adjuvant chemotherapy followed by RT. 90% of the 39 females treated by concurrent B-RT received whole breast irradiation (WBI) with a boost and 4 (10%) received post-mastectomy RT. Lymph node RT was delivered in 49% of the females with internal mammary chain irradiation. The mean duration of bevacizumab was 11.7 months. 38 (84%) females treated by RT alone received WBI with a boost and 16% of the females received post-mastectomy RT. Lymph node RT was delivered in 47% of the females with internal mammary chain RT in 31%. Grade 3 acute dermatitis was observed in 9% of patients receiving B-RT and 5% of patients receiving RT alone with no significant difference. 1 year after the completion of RT, the most common late grade 1-2 toxicities in the B-RT group were pain (18%), fibrosis (8%) and telangiectasia (5%). CONCLUSION: The concurrent bevacizumab with locoregional RT is associated with acceptable early and late 1-year toxicities in patients with BC. ADVANCES IN KNOWLEDGE: The largest series of this association.

Phase II randomized study of whole-brain radiation therapy with or without concurrent temozolomide for brain metastases from breast cancer.

BACKGROUND: To improve the therapeutic index of whole-brain radiation therapy (WBRT) in the treatment of brain metastases (BM) from breast cancer, we investigated the efficacy and safety of WBRT combined with temozolomide (TMZ) in this population. PATIENTS AND METHODS: This phase II multicenter prospective randomized study included patients with newly diagnosed intraparenchymal BMs from breast cancer, unsuitable for surgery or radiosurgery. All patients received conformal WBRT (3 Gy × 10-30 Gy), with or without concomitant TMZ administered at a dosage of 75 mg/m(2)/day during the irradiation period. The primary end point was objective response rate (ORR) 6 weeks after the end of treatment, defined as a partial or complete response on systematic brain MRI (modified WHO criteria). Secondary end points were progression-free survival (PFS) and overall survival (OS), neurologic symptoms, and tolerability. RESULTS: Between February 2008 and November 2010, 100 patients were enrolled in the study (50 in the WBRT + TMZ arm, 50 in the WBRT arm). Median age was 55 years (29-79). Median follow-up was 9.4 months [1.0-68.1]. ORRs at 6 weeks were 36% in the WBRT arm and 30% in the WBRT + TMZ arm (NS). In the WBRT arm, median PFS was 7.4 months and median OS was 11.1 months. In the WBRT + TMZ arm, median PFS was 6.9 months and median OS was 9.4 months. Treatment was well tolerated in this arm: the most common ≥grade 2 acute toxicity was reversible lymphopenia. CONCLUSION: WBRT combined with TMZ did not significantly improve local control and survival in patients with BMs from breast cancer. CLINICALTRIALS.GOV: NCT00875355.

Concurrent administration of trastuzumab with locoregional breast radiotherapy: long-term results of a prospective study.

This single-center prospective study aims to assess the outcomes and the toxicities related to the concurrent administration of trastuzumab (T) with adjuvant locoregional radiotherapy (RT) in localized breast cancer. Data of 308 patients were analyzed. T was delivered every 3 weeks (loading dose of 8 mg/kg, then 6 mg/kg) for 1 year. Left ventricular ejection fraction (LVEF), measured by echocardiography or myocardial scintigraphy, was considered as impaired when below 55%. Toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 3.0. Univariate and multivariate analyses were carried out using the Cox model. Median follow-up was 50.2 months (13.0-126.0). Median age at diagnosis was 52 years (25-83). Internal mammary node (IMN) RT was performed in 227 patients (73.7%). After completion of RT, 26 patients (8.4%) presented an impaired LVEF: 17 (5.5%) of grade 1, 7 (2.3%) of grade 2, and 2 (0.6%) of grade 3. At 48 months, locoregional control rate was 95% [95% CI 92; 98], and overall survival rate was 98% [95% CI 96; 100]. In univariate analysis, neither the treated breast side (p = 0.655) nor IMN RT (p = 0.213) exposed patients to LVEF alteration. In multivariate analysis, clinical lymph node involvement was associated with an increased risk of locoregional and distant recurrence (p = 0.016 and p = 0.007, respectively). In this prospective study, the toxicities of concurrent T with locoregional breast RT were acceptable and the outcomes favorable. Longer follow-up is warranted to confirm these results.

[Prospective monocentric study of the toxicity and the efficacy of concurrent trastuzumab and radiotherapy]. / Étude prospective monocentrique de la toxicité et de l'efficacité du trastuzumab concomitant à la radiothérapie.

PURPOSE: Prospective monocentric study of the toxicities related to concurrent administration of trastuzumab to breast radiotherapy. PATIENTS AND METHODS: One hundred and seventy-three patients were treated between June 2003 and March 2009 by concurrent trastuzumab with normofractionated radiotherapy. Trastuzumab was delivered every 3 weeks (8mg/kg in the first infusion then 6mg/kg) during a median time of 12 months (2-62). Left ventricular ejection fraction was assessed by echocardiography or cardiac scintigraphy at baseline, before and after radiotherapy, every 3 months for 1 year and annually. A left ventricular ejection fraction strictly lower than 55% was considered as altered. All toxicities were evaluated using Common Terminology Criteria for Adverse Effects version 3.0. RESULTS: Median follow-up was 52 months (17-88). Median age was 52 years (25-83). One hundred and thirty-four patients (77.5%) received radiotherapy to the internal mammary chain. Acute grade 1, 2 and 3 epithelitis was described in 132 (76.3%), 32 (18.5%) and six patients (3.4%), respectively. At 23 months, grade 1 and 2 fibrosis was observed in 31 and eight patients, respectively (18.8 and 4.6%). Left ventricular ejection fraction remained normal for 159 patients (91.9%) before radiotherapy. Among them, 18 (11.3%) experienced a left ventricular ejection fraction alteration, eight (5.0%) at the completion of radiotherapy. Congestive heart failure occurred in one patient (0.6%). CONCLUSIONS: Toxicities related to the association of trastuzumab to breast radiotherapy were mild. Further follow-up is warranted.