Shailendra Verma

E12534 Background: In the PALOMA-2 study, 1L PAL+L prolonged progression-free survival in women with estrogen receptor-positive/HER2- ABC vs placebo + L (hazard ratio 0.58; P< 0.001). Here we assess a cohort of Canadian pts treated with 1L PAL+L for ABC in an EAP study (NCT02142868). Methods: This was an open-label, single-arm study of US and Canadian postmenopausal women (N = 337) with HR+/HER2- ABC for whom 1L ET with L was deemed appropriate. The primary objective was to allow pt access to PAL in combination with L. PAL (125 mg/d orally [3 wk on, 1 wk off]) was administered with L (2.5 mg orally QD) until PAL was commercially available. Secondary objectives included safety and patient-reported outcomes (PROs). Results: 96/97 (99%) treated/enrolled Canadian pts were assessed for safety and PROs (treated pt characteristics: median age 62.5 y, white/Asian [89%/7%], metastatic sites bone/lung/liver [71%/25%/17%], ECOG PS 0-1/2 [93%/7%], 89% with prior systemic anticancer treatment [tx]). Median exposure was 4 x 28 d cycles of tx, and the median average PAL dose was 125 mg/d. All-causality treatment-emergent adverse events (AEs) were reported in 100% pts; 68% had grade 3/4 events, the most common events were neutropenia (61%), infections (3%), and alanine aminotransferase increase (3%). Grade 4 neutropenia and grade 3 febrile neutropenia were reported in 2% and 1% of pts, respectively. Due to AEs, PAL was temporarily discontinued in 59% and 31% had ≥1 dose reduction. The main reasons pts permanently discontinued from the study were sponsor study termination, 77%; objective progression, 11%; and AE related/unrelated to study drug, 6%/2%. All EQ-5D questions were completed by 96% pts at baseline and 85% by end of tx (EOT). At EOT, the median EQ-5D index and the EQ visual analog scale scores were not significantly changed from baseline. Conclusions: A safe and tolerable profile was observed for PAL+L in 1L treatment of Canadian pts with HR+/HER2− ABC, consistent with other studies. Sponsor Pfizer Clinical trial information: NCT02142868.

155 Background: Questions remain around the optimal use of bone-targeted agents (BTA) in patients with bone metastases (BM) from breast cancer (BC). In Canada pamidronate (PAM) is the most commonly used BTA in BC.We explored whether a switch to a more potent BTA, like zoledronic acid (ZA), in patients who remain at high risk of skeletal related events (SREs) despite PAM use is associated with significant palliative benefit. Methods: BC patients with high risk BM (prior SRE, bone progression, bone pain or levels of bone turnover marker serum C-telopeptide (sCTX) >400ng/L) despite >3 months of PAM use were eligible. Patients were randomized in a double–blind manner to either switch to ZA or continue on PAM every 4 weeks for 12 weeks. Primary outcome was the proportion of patients achieving a fall in sCTX at 12 weeks. Secondary outcomes were pain control (BPI and FACT-BP) and toxicity. Results 73 patients completed the study. Median age 61 years (range 37 – 87), prior duration of PAM use 10 months (range 3 – 118). sCTX levels for all patients at baseline, 372+/- 471, week 12, 209 +/-290. Proportion of patients achieving a fall in sCTX from week 0 to week 12, 26/31 (84%) in ZA arm, 17/30 (57%) in PA arm, p=0.0262. Two patients were unable to complete the study due to deterioration in renal function (both receiving PAM), four due to progressive disease (two receiving ZA, two PAM), two patients chose to discontinue the study before completion (both receiving ZA). Four patients (5%) had SRE’s during the study, two receiving ZA, two receiving PAM. Quality of life and pain analysis shows no difference between week 0 and week 12 scores in either arm. Toxicity was predominantly grade 1 and 2, numerically there were more adverse effects in the ZA arm than PAM. Conclusion Switching patients with high risk BM from PAM to ZA leads to a reduction in sCTX levels but may be associated with more toxicity. Quality of life and pain scores were similar between the two treatments. While the literature suggests that a reduction in sCTX may correlate with reduced rate of SREs, given the lack of symptom improvement a switching strategy cannot be recommended. NCT01907880 Clinical trial information: NCT01907880.

BACKGROUND: For patients with anthracycline‐pretreated metastatic breast carcinoma, capecitabine plus docetaxel significantly increased overall survival compared with docetaxel alone. The current study evaluated the cost‐effectiveness of the capecitabine/docetaxel combination versus docetaxel monotherapy, comparing the gain in quality‐adjusted survival with associated health care costs.METHODS: Patients were randomized to receive 21‐day cycles of oral capecitabine 1250 mg/m² twice daily, on Days 1–14, plus docetaxel 75 mg/m² Day 1 (n = 255), or docetaxel 100 mg/m² on Day 1 (n = 256). Health and cost outcomes in the two arms were compared, and cost‐effectiveness was estimated. Data on survival time and medical care resource use were prospectively collected in the trial. Costs associated with medical care resource use and quality‐of‐life adjustments were obtained from the published literature. The incremental cost‐effectiveness ratio was calculated as the cost per quality‐adjusted life year (QALY) gained.RESULTS: Capecitabine/docetaxel increased the median overall survival by 3 months compared with docetaxel alone (14.5 vs. 11.5 months). The mean quality‐adjusted survival was increased by 1.8 months in the capecitabine/docetaxel group. The total medical‐resource utilization cost per patient was 8.9% higher with the combination: $24,475 for combination therapy versus $22,477 for single‐agent docetaxel. The mean cost per QALY gained with combination therapy was $13,558 (standard deviation, $6742). Cost savings due to reduced docetaxel dose and hospital use were the major cost offsets with the combination. Sensitivity analyses showed that varying the mean hospital cost per day from the 5th to the 95th percentile resulted in cost‐utility ratios ranging from $20,326 to as low as $6360.CONCLUSIONS: Capecitabine/docetaxel was a cost‐effective treatment in patients with anthracycline‐pretreated advanced breast carcinoma, and had an incremental cost‐effectiveness ratio that compares very favorably with that of many other oncology therapies. Cancer 2005. © 2005 American Cancer Society.