A Randomized Placebo-Controlled Trial of the Anti-Nerve Growth Factor Antibody Tanezumab in Subjects With Cancer Pain Due to Bone Metastasis

Abstract

Background: This phase III, randomized, double-blind, placebo-controlled, parallel-group study assessed the efficacy and safety of tanezumab in subjects with cancer pain predominantly due to bone metastasis receiving background opioid therapy.

Methods: Subjects were randomized (stratified by (1) tumor aggressiveness and (2) presence/absence of concomitant anticancer treatment) to placebo or tanezumab 20 mg. Treatment was administered by subcutaneous injection every 8 weeks for 24 weeks (3 doses) followed by a 24-week safety follow-up period. The primary outcome was change in daily average pain in the index bone metastasis cancer pain site (from 0 = no pain to 10 = worst possible pain) from baseline to week 8.

Results: LS mean (SE) change in pain at week 8 was -1.25 (0.35) for placebo (n = 73) and -2.03 (0.35) for tanezumab 20 mg (n = 72). LS mean (SE) [95% CI] difference from placebo was -0.78 (0.37) [-1.52, -0.04]; P = .0381 with α = 0.0478. The number of subjects with a treatment-emergent adverse event during the treatment period was 50 (68.5%) for placebo and 53 (73.6%) for tanezumab 20 mg. The number of subjects with a prespecified joint safety event was 0 for placebo and 2 (2.8%) for tanezumab 20 mg (pathologic fracture; n = 2).

Conclusion: Tanezumab 20 mg met the primary efficacy endpoint at week 8. Conclusions on longer-term efficacy are limited since the study was not designed to evaluate the durability of the effect beyond 8 weeks. Safety findings were consistent with adverse events expected in subjects with cancer pain due to bone metastasis and the known safety profile of tanezumab. Clinicaltrials.gov identifier: NCT02609828.

Keywords: cancer pain; nerve growth factor; randomized controlled trial; tanezumab.

Figure 1.

Trial design. SC, subcutaneous. ^aTelephone contact. ^bTelephone contact except in Japan (clinic visit). The screening period included a baseline assessment period consisting of the 5 days immediately prior to the randomization (1st dosing) visit. During this time, the subject’s baseline pain value was determined, and the subject’s background opioid regimen was assessed to ensure it sufficiently minimized the need for opioid immediate-release rescue and was tolerable.

Figure 2.

Subject disposition. mITT, modified intent-to-treat; SC, subcutaneous. ^aOther screened but not randomized indicates subjects who were screened but not randomized for a reason not related to a specific eligibility criterion. ^bThe study protocol initially included 3 treatment arms (SC placebo, SC tanezumab 10 mg, and SC tanezumab 20 mg). After initiation of the study, the protocol was amended to discontinue the tanezumab 10 mg dose arm. Nine subjects received tanezumab 10 mg and either completed the treatment phase or discontinued the treatment phase prior to implementation of the amendment; these subjects are in the tanezumab 10 mg group in the figure above. One subject received tanezumab 10 mg and was in the treatment phase at the time of implementation of the amendment; this subject was administered 20 mg of for all remaining doses and is included in the tanezumab 10/20 mg group in the figure above. ^cIncludes all subjects treated with placebo or tanezumab (including the tanezumab 10 mg and tanezumab 10/20 mg groups). ^dThe mITT was the primary efficacy analysis set and includes all subjects randomized to either placebo or tanezumab 20 mg who received at least 1 dose of SC study medication (excludes the tanezumab 10 mg and tanezumab 10/20 mg groups).

Figure 3.

Change in daily average (A) and worst (B) pain at the index bone metastasis cancer pain site. Scores range from 0 to 10, with higher scores indicating greater pain severity. LS, least squares; SC, subcutaneous; SE, standard error. *P < .05, **P < .01.

Figure 4.

Possible role of NGF in pain due to cancer metastasis to bone. NGF = nerve growth factor; TrkA = tropomyosin receptor kinase A.