Background: Patients with brain metastases (BM) from human epidermal growth factor receptor 2 (HER2)-positive breast cancer represent a difficult-to-treat population. Trastuzumab emtansine (T-DM1) has shown potential activity in this subset of patients in small clinical series. Patients and methods: KAMILLA is an ongoing, phase IIIb study of T-DM1 in patients with HER2-positive locally advanced/metastatic breast cancer with prior HER2-targeted therapy and chemotherapy. Patients received T-DM1 3.6 mg/kg every 3 weeks (intravenously) until unacceptable toxicity, withdrawal of consent, or disease progression. Tumor response and clinical outcomes in patients with baseline BM were evaluated in this post hoc, exploratory analysis. The main outcome measures were best overall response rate (complete response þ partial response) and clinical benefit rate (complete response þ partial response þ stable disease lasting !6 months) by RECIST v1.1 criteria, progression-free survival, overall survival, and safety. Results: Of 2002 treated patients, 398 had baseline BM. In 126 patients with measurable BM, the best overall response rate and clinical benefit rate were 21.4% [95% confidence interval (CI) 14.6e29.6] and 42.9% (95% CI 34.1e52.0), respectively. A reduction in the sum of the major diameters of BM !30% occurred in 42.9% (95% CI 34.1e52.0), including 49.3% (95% CI 36.9e61.8) of 67 patients without prior radiotherapy to BM. In the 398 patients with baseline BM, median progression-free survival and overall survival were 5.5 (95% CI 5.3e5.6) months and 18.9 (95% CI 17.1e21.3) months, respectively. The adverse event profile was broadly similar in patients with and without baseline BM, although nervous system adverse events were more common in patients with [208 (52.3%)] versus without [701 (43.7%)] baseline BM. Conclusion: This exploratory analysis of patients with HER2-positive metastatic breast cancer and BM enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population. T-DM1 should be explored further in this setting. Trial registration: ClinicalTrials.gov identifier: NCT01702571.

The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects. The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG, particularly in the final part of chemotherapy treatment.

Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.

No abstract

Weekly docetaxel is an active regimen in metastatic breast cancer with comparable efficacy to 3 weekly docetaxel. Although both schedules were well tolerated, weekly docetaxel appears to have a more favourable toxicity profile.

Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) for 4 cycles) followed either by D (docetaxel 100 mg/m(2) × 4 cycles; EC-D) or DCb (docetaxel 75 mg/m(2) plus carboplatin AUC 6 × 4 cycles; EC-DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC-D, 48 EC-DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC-D and 14 patients (30 %) with EC-DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56-83) in the EC-D arm and 77 % (95 % CI 65-87) in the EC-DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC-D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.

LBA4518 Background: Approximately half of patients with resected invasive bladder cancer will die within the first three years after surgery due to disease relapse, most of the recurrences being systemic. We have studied in a randomized phase III trial the role of 4 courses of the PGC triplet as compared to observation in this clinical setting. Methods: Eligibility criteria included: (1) resected high-risk muscle invasive bladder carcinoma (pT3-4 and/or pN+), (2) ECOG PS 0-1, (3) adequate renal function (CrCl > 50 ml/min), (4) ≤ 8 weeks post-cystectomy, (5) no relevant co-morbidities, and (6) signed informed consent. Eligible patients were assigned to observation or 4 courses of PGC (P 80 mg/m2 d1 and 8, G 1000 mg/m2 d1 and 8 and C 70 mg/m2 d1) q21 days. The primary objective was overall survival (OS). Results: The study was open in July 2000 and prematurely closed due to poor recruitment in July 2007, with 142 patients randomized (74 to observation and to 68 to PGC treatment). Baseline characteristics were well balanced among study arms. Median age was 63 yrs, pT3-4N0: 44%, anyTpN+:56%, PS 0: 59%, median time cystectomy-randomization: 48 days (14-91). In the PGC arm 76% of pts completed all 4 courses of therapy. Main Gr 3-4 toxicities were neutropenia 41%, febrile neutropenia 8%, thrombocytopenia 14%, anemia 5%, fatigue 14%, alopecia 10%, vomiting 8%, renal 5%. There was one toxic death (sepsis). At a median follow up of 30 months (range 1-95), 69 patients have died (45 in control arm and 24 in PGC arm). OS (ITT population) was significantly prolonged in the PCG arm (median NR; 5yr OS: 60%) compared to observation (median 26m; 5yr OS: 31%) (p<0.0009). DFS (p<0.0001), TTP (p<0.0001) and disease specific survival (p<0.0002) were also superior in the PGC arm. Conclusions: The results of this study strongly suggest that adjuvant PGC improves OS and DFS following cystectomy in high risk invasive bladder cancer. As the study was prematurely closed, the power for firm conclusions is however limited. [Table: see text]

Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.