Anamorelin Plus Chemo Is Tolerable in Metastatic Urothelial Carcinoma

Treatment with the ghrelin receptor agonist anamorelin was deemed well tolerated and induced an increase in serum IGF-1 levels that may be associated with efficacy in patients with metastatic urothelial carcinoma who were simultaneously receiving platinum-based chemotherapy, according to findings from a Japanese clinical trial (jRCTs041210041) presented during the 2025 ESMO Asia Congress.¹

No significant differences in the rates of treatment-related adverse effects (TRAEs) were reported between patients who received anamorelin with chemotherapy (n = 20) compared with those who received chemotherapy plus best supportive care (BSC; n = 18). Instances of hyperglycemia and abnormal electrocardiogram findings observed in the anamorelin group rapidly improved following discontinuation of the agent.

The median progression-free survival (PFS) in the anamorelin group was 8.0 months compared with 7.5 months in the control group (P = .56). The median overall survival (OS) values were 22.1 months and 31.4 months, respectively (P = .45).

“An increase in serum IGF-1 levels induced by anamorelin may be associated with its efficacy,” Yoshihisa Mimura, MD, of the Department of Clinical Pharmaceutics at Nagoya City University Graduate School of Medical Sciences in Japan, and his coauthors wrote in a poster presentation of the data. “Administration of anamorelin in the earlier stages of cancer cachexia may provide greater benefit to patients.”

What was the design of the study investigating anamorelin in metastatic urothelial carcinoma?

The prospective, multicenter, randomized clinical study evaluated the efficacy and safety of anamorelin in patients with recurrent or metastatic urothelial carcinoma who had received prior frontline chemotherapy.² Eligible patients needed to be at least 20 years of age, have histologically and/or cytologically confirmed disease, and have an ECOG performance status of 0 to 2.

Patients were randomly assigned 1:1 to receive anamorelin at 100 mg daily over 12 weeks or BSC, both in combination with systemic chemotherapy.

The primary outcome of the study was change in prealbumin levels. Secondary outcomes included changes in albumin levels, body weight, skeletal muscle mass index, and IGF-1 levels. TRAEs, PFS, and OS were also assessed.¹

At baseline, the median ages in the control and anamorelin arms were 70 years (range, 43-87) and 74 years (range, 60-88), respectively. Most patients in both groups were male (77.8% vs 90.0%), had an ECOG performance status of 0 (94.4% vs 70.0%), and had lymph node metastases (88.9% vs 90.0%). Patients in both arms had previously undergone neoadjuvant/adjuvant chemotherapy (22.2% vs 30.0%) and radical resection (22.2% vs 30.0%).

What were the additional safety and efficacy data from the study of anamorelin plus chemotherapy in urothelial carcinoma?

The objective response rate in the anamorelin arm was 60.0% (95% CI, 36%-81%) compared with 55.6% (95% CI, 31%-79%) in the control arm (P = .75). The respective complete response rates were 5.0% and 0%. Anamorelin was found to be significantly associated with increased change from baseline in IGF-1 levels after 1 week of treatment (P < .05).

All patients in both arms experienced any-grade TRAEs. Grade 3 to 4 TRAEs occurred at respective rates of 88.9% and 90.0% in the control and anamorelin arms. The most common any-grade TRAEs included anemia (100.0% vs 95.0%), thrombocytopenia (88.9% vs 90.0%), and fatigue (72.2% vs 85.0%).

“The safety profile [of anamorelin] was consistent with that observed in previous clinical trials,” Mimura and his coauthors wrote. “Anamorelin was well tolerated in patients with metastatic urothelial carcinoma.”

Disclosures: Mimura reported no conflicts of interest related to the study.

References

1. Mimura Y, Naiki T, Odagiri K, et al. Safety and efficacy of anamorelin for patients with metastatic urothelial carcinoma receiving systemic chemotherapy. Ann Oncol. 2025;36(suppl 4): S1958-S1977. doi:10.1016/annonc/annonc1992
2. Odagiri K, Mimura Y, Naiki T, et al. Efficacy and safety of anamorelin in patients with metastatic urothelial carcinoma receiving systemic chemotherapy: a randomized controlled study. Oncologist. 2025;30(7):oyaf167. doi:10.1093/oncolo/oyaf167