Abstract only
4065
Background: The international phase III study ToGA has recently shown that TRA is effective in prolonging survival in HER2-positive MGC. However, few data are available for TRA as ...part of routine clinical practice. Methods: This non-interventional observational study was conducted to evaluate the efficacy, safety and feasibility of TRA in previously untreated pts with HER2-positive MGC. Results: Between Apr 2010 and Jan 2012, data from 110 pts were collected. All pts were evaluable for safety. Baseline pt characteristics were as follows: median age 63 yrs (range 29–88); gender (male 70%; female 29%); ECOG PS (0: 25%; 1: 50%; 2: 15%; 3: 5%); distant mets (91%); liver mets (54%), lymph node mets (35%); peritoneal carcinomatosis (23%). The median duration of TRA treatment was 4.4 months (0–17.1). According to the schedule of chemotherapy TRA was administered every 2–3 wks in a median dose of 4–6 mg/kg BW. Only 28% of pts received TRA according to the label in combination with cisplatin and 5-FU or capecitabine. The remainder received: cisplatin, 5-FU and leucovorin (17%); 5-FU, leucovorin, oxaliplatin and docetaxel (8%); 5-FU, leucovorin and oxaliplatin (7%); capecitabine (6%); other combinations (25%); TRA monotherapy (7%). Although most pts didn’t receive cisplatin-based therapy, preliminary median progression-free survival was 6.8 months, thus comparable to the ToGA data. Most common adverse events (AEs, all grades) were diarrhoea (7%), vomiting (5%) and nausea (5%). Most common grade 3/4 AEs were vomiting (3%), nausea (2%) and fatigue (2%). Health-related quality of life as assessed by EORTC QLQ-C30 and QLQ-STO22 remained stable during observation time. An updated analysis of approx. 200 pts will be presented at the meeting. Conclusions: TRA combined with diverse chemotherapies is safe and effective in the routine treatment of MGC. Cisplatin-free less toxic regimens are feasible and equally effective. The results are in line with those from the ToGA trial and suggest that treatment with TRA should be regarded as standard of care for pts with HER2-positive MGC.
Abstract only
4539
Background: Several retrospective studies have investigated the sequential use of SO and SU. Some smaller trials support the use of SO followed by SU forming the rationale for this ...study. Methods: Pts with metastatic RCC unsuitable for cytokines without prior systemic therapy, ECOG PS 0/1, MSKCC score low or intermediate, and ≥1 measurable lesion (CT/MRI every 12 weeks) were randomized to SO->SU or SU->SO in standard dosage (primary endpoint total PFS from randomization to event during 2
nd
line therapy). Treatment continues until progression or intolerability. Monitoring includes echocardiography and NT pro-BNP. Results: Baseline characteristics of 361 randomized pts (116 completed) are balanced between arms. Safety data of 333 pts are evaluable. AE occurring in >10% of pts are listed in tab. 1. Left-ventricular ejection fraction (LVEF) at screening, switch of treatment, and end of study are given in tab. 1. AE occurred in 93.4% and 92.8%; grade 3/4 AE in 59.9% and 50%; and SAE in 46.7% and 42.2% in the SO->SU and SU->SO arm, respectively. Updated results will be presented. Conclusions: AE frequencies are higher in 1
st
than in 2
nd
line treatments. Typical AE profiles for SO and SU are observed. LVEF values are in a similar range. Table: see text
Abstract only
556
Background: RAD001 is an orally bioavailable rapamycin ester analogue, which acts by selectively inhibiting mTOR (mammalian target of rapamycin), a key player in downstream ...signaling of different pathways. In vitro, RAD stops formation and activity of osteoclasts. Treating progressive bone metastases in breast cancer (bc) with RAD seems reasonable. Methods: We evaluated RAD in a placebo-controlled, phase II, randomized discontinuation study in bc patients (pts) with bone metastases only. Pts were eligible if they had HER2-negative, hormone-receptor (HR)-positive or –negative bc, with a maximum of 2 previous lines of endocrine therapy (ET) and 1 previous line of chemotherapy (CT). All pts received zoledronate and pts with HR-positive bc could receive ET. All pts started with RAD during a run-in phase of 8 weeks. Pts with stable disease were randomized to RAD or placebo; pts with response continued with RAD and pts with progression went off study. Primary outcome was time to progression (TTP) in pts being stable on 8 weeks of RAD. It was assumed that placebo would obtain a median TTP of 8 weeks which would be increased to 16 weeks, thus requiring 76 randomized pts. It was expected that 70% of all pts would have stable disease after the run-in phase. Overall, 110 pts were needed. Due to slow recruitment and dysbalance between randomized and discontinued pts, recruitment stopped in 12/ 2010. Results: From 11/06 until 12/10, 89 pts were enrolled. Median age was 59.5 years. 93% had HR-positive disease. 15% had prior chemotherapy; 58% had prior ET for metastases. 1/3 received concomitant ET. Three pts did not start therapy, 41 discontinued during run-in phase, 32 due to progression. Six continued as responder. 39 pts with SD after run in phase were randomized to RAD or placebo. Twenty-seven stopped due to progression; 9 discontinued due to AE, 4 are still on treatment. 15 pts had 20 serious adverse events; 1 hyperglycemia and one alveolitis. The TTP in patients with RAD was 8.5 months vs. 2.9 months with placebo (HR: 0.559; 95% CI 0.284-1.10 p=0.092. Conclusions: Pts with bone metastases only had a longer TTP on RAD compared to pts on placebo. Overall 7/89 showed a sustained response on RAD + zoledronate ± ET.
Complex platinum (Pt) compounds are known as occupational respiratory sensitizers whereas their role in skin exposure is unclear. In this study, both skin irritation and induction of contact ...hypersensitivity by halide Pt salts were characterized in mice. Repeated application of Na
2PtCl
6 (5% in acetone) to both ears of naive BALB/c mice induced activation of the draining auricular lymph nodes. Flow cytometric analysis revealed a striking increase in the number of lymph node cells expressing proliferating cell nuclear antigen. In separate experiments, Na
2PtCl
6 or acetone were applied only to the right ear of mice on 4–8 consecutive days and the animals were challenged on the left ear 6 days later. Ear thickness was determined before and 0.5, 24, 48, and 72 h after challenge with 0.5 or 2% Na
2PtCl
6 or acetone. Maximal swelling of the left ear was recorded at 48 h in Pt-sensitized mice challenged with 2% Na
2PtCl
6. Furthermore, the concentration of Na
2PtCl
6 required for sensitization caused an irritant reaction as demonstrated by significant swelling of the right ear. These data support the concept that both irritant and allergic contact dermatitis to halide Pt salts may occur in humans. Concerning skin exposure to halide Pt salts, Pt-induced irritant reactions resulting from an intrinsic adjuvant’s activity of the compound could be a prerequisite for sensitization.
