Biologics are essential to oncology care. As patents for older biologics begin to expire, the United States is developing an abbreviated regulatory process for the approval of similar biologics (biosimilars), which raises important considerations for the safe and appropriate incorporation of biosimilars into clinical practice for patients with cancer. The potential for biosimilars to reduce the cost of biologics, which are often high-cost components of oncology care, was the impetus behind the Biologics Price Competition and Innovation Act of 2009, a part of the 2010 Affordable Care Act. In March 2011, NCCN assembled a work group consisting of thought leaders from NCCN Member Institutions and other organizations, to provide guidance regarding the challenges health care providers and other key stakeholders face in incorporating biosimilars in health care practice. The work group identified challenges surrounding biosimilars, including health care provider knowledge, substitution practices, pharmacovigilance, naming and product tracking, coverage and reimbursement, use in off-label settings, and data requirements for approval.

BACKGROUND To determine the potential efficacy of targeting both the tumor and bone microenvironment in patients with castration-resistant prostate cancer (CRPC), we conducted a phase 1/2 trial combining docetaxel with dasatinib, an oral SRC inhibitor. METHODS In phase 1, 16 men received dasatinib 50–120 mg once daily (QD) and docetaxel 60–75 mg/m2 every 21 days (Q21D). In phase 2, 30 additional men received dasatinib 100 mg QD/docetaxel 75 mg/m2 Q21D. Efficacy endpoints included changes in prostate-specific antigen (PSA), measurable disease, bone scans, and markers of bone metabolism. Safety and pharmacokinetics were also studied. RESULTS Combination dasatinib and docetaxel therapy was generally well tolerated. Thirteen of 46 patients (28%) had a grade 3/4 toxicity. Drug–drug interactions and a maximum tolerated dose were not identified. Durable 50% PSA declines occurred in 26/46 patients (57%). Of 30 patients with measurable disease, 18 (60%) had a partial response. Fourteen patients (30%) had disappearance of a lesion on bone scan. In bone-marker assessments, 33/38 (87%) and 26/34 (76%) had decreases in urinary N-telopeptide or bone-specific alkaline phosphatase levels, respectively. Twenty-eight patients (61%) received single-agent dasatinib following docetaxel discontinuation and had stabilization of disease for an additional 1–12 months. CONCLUSIONS The high objective response rate and favorable toxicity profile are promising and justify randomized studies of docetaxel and dasatinib in CRPC. Parallel declines in levels of PSA and bone markers are consistent with co-targeting of epithelial and bone compartments of the cancer. Treatment with single-agent dasatinib following docetaxel cessation warrants further study.

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5061 Background: Dasatinib, a potent inhibitor of SRC family kinases, inhibits in vitro prostate cancer cell proliferation and migration. Consistent with those findings are the clinical observations that osteoclast activity and bone turnover are downregulated in patients treated with dasatinib. We report promising preliminary results of dasatinib in combination with docetaxel (D) for treatment of metastatic castration-resistant prostate cancer (CRPC). Methods: Male pts with progressive CRPC and castrate levels of testosterone (≤50 ng/dL) requiring chemotherapy were enrolled. Escalating doses of dasatinib (50–120 mg QD) and D (60–75 mg/m2 Q 21 days) were evaluated (n = 16) followed by enrollment of 30 pts at the phase 2-selected dose (100 mg dasatinib QD + D at 75 mg/m2 Q 21 days). Continuation of bisphosphonates was permitted; anti-androgens were discontinued. Primary endpoint (Ph. 2) was to determine drug-drug interactions. Secondary endpoints were: changes in PSA, bone scans and tumor size, bone metabolism [urinary N-telopeptide (uNTX) and bone alkaline phosphatase (BAP)] and PK. Results: 46 pts were treated with 28 pts still on therapy. Median treatment duration (n = 18, pts off study) was 4.2 months (0.13–9.63). Preliminary analysis showed no interaction between dasatinib and D. PSA response was seen in 13/32 (41%) pts, clinical benefit (PR + SD) for RECIST-evaluable pts was 21/21, [7 PR, 5 uPR and 4 SD (at ≥21 wks) and 5 SD at ≥6 wk)]. Of 31 pts with bone scans, 30 patients had a best response of either improved (32%) or stable (65%) at ≥6 weeks. For pts with measurable bone markers levels, 12/26 (46%) had a ≥35% decrease in uNTX and 17/24 (71%) had a decrease in BAP from baseline. 6 of 42 pts experienced ≥ grade 3 adverse events (AEs), including fatigue, myelosuppression and pleural effusion (n = 1). Most common grade 1/2 AEs were fatigue, dysgeusia, GI, and skin disorders. Conclusions: Dasatinib and D at doses up to 120 mg QD and 75 mg/m2 are safe with manageable toxicities and no drug-drug interactions. These data confirm the antitumor and antiosteoclast activity of dasatinib in combination with D and serve as the basis for the ongoing phase III study of this combination. [Table: see text]