1. Nalley, Catlin

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New research suggests that subcutaneous tanezumab improved metastatic cancer-related bone pain when compared with placebo, according to data recently presented at the ESMO Congress 2021 (Abstract LBA62). The researchers also reported an adverse event profile that was generally consistent with previous studies of tanezumab.

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"Bone is among the most common sites of cancer metastasis and the most common cause of cancer-related pain," stated study author Marie Fallon, MD, FRCP, Professor at the University of Edinburgh, and her colleagues. "Despite a range of treatment options, about 25 percent of patients with painful bone metastases suffer from uncontrolled pain."


During the conference, Fallon reported findings from a Phase III, randomized, double-blind, placebo-controlled trial that was designed to assess the efficacy and safety of subcutaneous tanezumab-a monoclonal antibody against nerve growth factor-in subjects with moderate to severe cancer pain predominantly due to bone metastasis who were receiving background opioid therapy.


Research Specifics

The study included participants from 15 countries (Europe, South America, Asia-Pacific regions) who were randomized to receive either double-blind subcutaneous placebo (N=73) or tanezumab 20 mg (N=72) every 8 weeks for 24 weeks (baseline, week 8, and week 16) while they continued optimized background opioid therapy. A 24-week safety follow-up period occurred after the 24-week treatment period, the study authors noted.


"Adult subjects with a diagnosis of cancer having metastasized to bone or with multiple myeloma, an average pain intensity score >=5 (on a scale from 0=no pain to 10=worst possible pain) at the index bone metastasis cancer pain site, and who were receiving optimized background opioid therapy for their metastatic bone cancer-related pain were eligible for the study," Fallon outlined during her presentation.


"The primary endpoint was change in daily average pain intensity at the index bone metastasis cancer pain site from baseline to 8 weeks and it was evaluated by analysis of covariance," she continued. "Adverse events and prespecified joint safety events adjudicated by an external expert committee were also assessed during the study."


The prespecified joint safety events included rapidly progressive osteoarthritis type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture.


"Subject demographics and clinical characteristics were mostly similar between the placebo and tanezumab treatment groups," said Fallon. "The ratio of males to females was higher in the tanezumab group than in the placebo group. The population was predominantly white with breast, prostate, and lung carcinoma being the most common primary cancer types."


Key Takeaways

"Tanezumab 20 mg met the primary endpoint by demonstrating significantly (p=0.0381 with [alpha]=0.0478) greater improvement in daily average pain intensity at the index bone metastasis cancer pain site at week 8 compared with placebo," Fallon reported.


"Significant differences in favor of tanezumab were also noted at Weeks 1,2,4, and 6," she added. "However, differences between the tanezumab and placebo groups were not statistically significant past Week 8 though the study was not powered to test the durability of the analgesic efficacy."


During the treatment period, the researchers observed that the adverse event profile of tanezumab 20 mg was generally consistent with the adverse events expected in individuals with cancer pain due to bone metastasis as well as the known safety profile of this agent.


"Adverse events, serious adverse events, and severe adverse events were more frequent with tanezumab 20 mg than with placebo during the treatment period, while discontinuations due to adverse events-from the study and from the study treatment-were more frequent with placebo," said Fallon.


"The most common adverse events in each group were anemia (placebo=12.3%, tanezumab=8.3%), arthralgia (placebo=8.2%, tanezumab=8.3%), and prostate cancer (placebo=8.2%, tanezumab=8.3%)," she continued. "The frequency of these three events in the tanezumab group was similar to, or less than, the frequency in the placebo group."


The proportion of subjects adjudicated with a pre-specified joint safety event during the study was 0 percent for the placebo arm and 2.8 percent for the tanezumab 20 mg arm. The two events in the tanezumab 20 mg were characterized as pathological fracture near the site of bone metastases, Fallon reported.


Additionally, she noted there were 23 deaths reported in the placebo group (31.5%) compared to 21 among the subjects who received tanezumab 20 mg (29.2%). None were considered treatment related by the investigators.


"[In conclusion], the study achieved the primary objective by demonstrating superior analgesic efficacy of tanezumab 20 mg versus matching placebo at Week 8," Fallon summarized. "Further, the adverse event profile of tanezumab 20 mg during the treatment period was generally consistent with adverse events expected in subjects with cancer pain due to bone metastasis and the known safety profile of tanezumab.


While she noted that the durability of efficacy beyond 8 weeks has not been demonstrated and pathologic fractures were only noted in the tanezumab 20 mg treatment group, Fallon concluded, "Overall, these data demonstrate the potential of a nerve growth factor inhibitor, such as tanezumab, to reduce pain caused by bone metastases."


Catlin Nalley is a contributing writer.