LBA62 - Efficacy and safety of tanezumab in subjects with cancer pain predominantly due to bone metastasis receiving background opioid therapy

Background

Despite a range of treatment options, about 25% of patients with painful bone metastases suffer from uncontrolled pain. This Phase 3, randomized, double-blind, placebo-controlled trial (24-week treatment/24-week follow-up) examined the efficacy and safety of tanezumab, a monoclonal antibody against nerve growth factor, in subjects with moderate to severe cancer pain due to bone metastasis or multiple myeloma receiving background opioid therapy.

Methods

Subjects from 15 countries (Europe, South America, Asia-Pacific regions) were randomized and received double-blind subcutaneous placebo or tanezumab 20 mg at baseline, week 8, and week 16 while continuing optimized opioid therapy. The primary endpoint was change in daily average pain intensity (0 = no pain to 10 = worst possible pain) at the index bone metastasis cancer pain site from baseline to week 8, evaluated via analysis of covariance. Adverse events (AEs) and pre-specified joint safety events (rapidly progressive osteoarthritis [RPOA] type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture; adjudicated by an external expert committee) were also assessed.

Results

Tanezumab 20 mg (N =72) met the primary endpoint by demonstrating significantly (p = 0.038 with α = 0.048) greater improvement in daily average pain intensity at the index bone metastasis cancer pain site at week 8 compared with placebo (N = 73). LS mean (95% CI) change in pain was -1.25 (-1.94, -0.55) for placebo and -2.03 (-2.73, -1.33) for tanezumab 20 mg. Differences past week 8 were not statistically significant. During the treatment period, the AE profile of tanezumab 20 mg was generally consistent with AEs expected in subjects with cancer pain due to bone metastasis and the known safety profile of tanezumab. The proportion of subjects adjudicated with a pre-specified joint safety event during the study was 0% for placebo and 2.8% for tanezumab 20 mg (pathological fracture near the site of bone metastasis, n = 2). No events of RPOA were reported.

Conclusions

Tanezumab 20 mg improved metastatic cancer-related bone pain compared with placebo and the AE profile was generally consistent with previous studies of tanezumab.

Clinical trial identification

NCT02609828.

Editorial acknowledgement

Medical writing assistance was provided by Matt Soulsby, PhD, CMPP of Engage Scientific Solutions and was funded by Pfizer Inc and Eli Lilly & Company.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc and Eli Lilly & Company.

Disclosure

M. Fallon: Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Other, Investigator for the study: Pfizer and Eli Lilly & Company. M. Sopata: Financial Interests, Personal, Other, Investigator for this study: Pfizer and Eli Lilly & Cmpany; Financial Interests, Personal, Other, National coordinator for this study: Pfizer and Eli Lilly & Company. E. Dragon: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. M.T. Brown: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. L. Viktrup: Financial Interests, Personal, Full or part-time Employment: Eli Lilly & Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly & Company. C.R. West: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. K. Hamlett: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. W. Bao: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. A. Agyemang: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer.