Background Abiraterone + prednisone (abiraterone) and enzalutamide are both indicated for the treatment of metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the best sequence in which to utilize both agents as well as their second-line efficacy. Methods In this multicentre, randomized, open-label phase II crossover trial conducted across 6 cancer centres in British Columbia, Canada, patients ≥ 18 years with newly-diagnosed mCRPC without neuroendocrine differentiation and ECOG performance status ≤ 2 were randomized 1:1 using simple randomization to receive abiraterone 1000 mg orally daily plus prednisone 5 mg orally twice daily followed by enzalutamide 160 mg orally daily (arm A), or the opposite sequence (arm B). Primary endpoints were time to second PSA progression and PSA response rate (≥ 30% decline) on second-line therapy, analyzed by intention-to-treat in randomized patients and patients that crossed over, respectively. The trial is registered with ClinicalTrials.gov, number NCT02125357. The trial is completed and final analyses are reported here. Findings 202 patients were randomized (101 to each arm) between October 21, 2014 and December 13, 2016. At the time of data cutoff 73 and 75 patients had crossed over in arm A and B, respectively. Time to second PSA progression was longer in arm A (median 19•3 vs 15•2 months, HR = 0•66, 95% CI 0•45-0•97, p = 0•036), at a median followup of 22•8 months (IQR 10•3-33•4). Second-line PSA response rates were 36% for enzalutamide and 4% for abiraterone (p < 0•0001). The most common grade 3-4 adverse events were hypertension (27 [27%] of 101 patients in arm A vs 18 [18%] of 101 in arm B) and fatigue (10 [10%] vs 4 [4%]). Serious adverse events were reported in 15 (15%) of 101 patients in arm A and 20 (20%) of 101 in arm B. There were no treatment related deaths.

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#5118 Background: The role of trastuzumab either concurrent or sequential with adjuvant chemotherapy have clearly demonstrated significant benefits in early stage HER-2 positive breast cancer. There is now an accumulation of phase II and III trials also demonstrating improved pathological complete responses (pCR) in HER-2 positive breast cancer with neoadjuvant trastuzumab concurrent with chemotherapy. The number of patients on these trials are significantly fewer, and many of these trials are a mixture of primary operable and LABC. We have completed a multi-centre phase II trial of neoadjuvant chemotherapy and trastuzumab in HER-2 positive LABC.&#x2028; Methods: Women with HER-2 positive (IHC 3+ or FISH+) stage IIB-IIIC breast cancer were enrolled. Treatment consisted of 4 cycles of FEC100 (5-FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) followed by 4 cycles of TCH (Docetaxel 75 mg/m2, carboplatin AUC 6, trastuzumab 8 mg/kg loading then 6 mg/kg q3 weekly). Trastuzumab was also continued adjuvantly for 9 months following chemotherapy and surgery. Cardiac monitoring every 3 months was mandated. A correlative translational component with baseline and interval biopsies and serum collection was also performed.&#x2028; Results: A total of 30 patients (3 stage IIB; 14 IIIA; 10 IIIB and 3 IIIC) over a 3 year time period in 4 centres were accrued. Median age was 49 years (26-77 years). 60% of tumours were ER negative. There was one clinical CHF and 2 asymptomatic falls in LVEF requiring early discontinuation of trastuzumab. There were 3 episodes (10%) of febrile neutropenia. Seven patients underwent adjuvant radiotherapy prior to surgery. The pCR rate (breast and axilla) for the entire study population was 60% (18/30). There have been 3 recurrences so far (all biopsy proven) – of which 2 were brain metastases only. Further details on toxicity and changes in LVEF will be presented.&#x2028; Conclusions: This multi-centre phase II trial clearly demonstrates significant activity (pCR 60%) for neoadjuvant anthracyclines followed by concurrent taxane, platinum and trastuzumab in a HER-2 positive LABC population. Overall the treatment regimen was well tolerated. Brain metastases however appear to be a common site of relapse in this high risk patient population and further treatment strategies directed at this site should be investigated. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5118.

598 Background: Anthracyclines and taxanes are now standard of care for LABC. Phase III trials have demonstrated pathological complete responses of the breast (pCR) of 20–34% in studies of primary operable and LABC. Recent trials in the HER-2 negative population reported pCR rates of 20–29%.We have completed a multi-centre phase II trial of a neoadjuvant sequential anthracycline and taxane combination regimen in a HER-2 negative LABC population. Methods: Women with HER-2 negative stage IIB-IIIC breast cancer were enrolled. Treatment consisted of 4 cycles of FEC100 (5-FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) followed by 4 cycles of XT (docetaxel 75 mg/m2 and capecitabine 1,000 mg/m2 PO BID x 14 days q3 weekly). Hormone receptor positive cases were prescribed standard endocrine therapy. A correlative translational component with baseline and interval biopsies and serum collection was also performed. Results: A total of 51 patients (27% stage IIB; 43% IIIA; 20% IIIB; and 10% IIIC) were accrued across 4 BCCA centres from November 2004-December 2007. Median age was 54 years (33–67 years). 59% of tumours were ER positive. There were no primary progressors on FEC100, though 2 patients had significant toxicities requiring early discontinuation. 3 patients (6%) developed clinical progression on XT. The majority of patients (79%) on XT required a dose reduction or delay. There were 5 episodes (10%) of febrile neutropenia. 15 patients (29%) underwent adjuvant radiotherapy prior to surgery. The pCR rate (breast and axilla) for the entire study population was 22% (11/51). In the ER+ and triple negative subtypes the pCR (breast and axilla) was 13% and 42%, respectively. Conclusions: This multi-centre phase II trial demonstrates activity for neoadjuvant anthracyclines followed by combination docetaxel/capecitabine in a HER-2 negative LABC population. Though the pCR rate was greater in the triple negative cohort, significant improvements are still required across the biological subtypes in HER-2 negative LABC. [Table: see text]

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