No significant difference in handgrip strength was observed between treatment arms in the two ROMANA trials.16,17 Handgrip strength may not be a reliable measure of functional changes in muscle or strength in patients with anorexia/cachexia, and other recent studies of medications for anorexia/cachexia have also failed to show improvements in muscle strength despite increases in LBM.20-22
In ROMANA 1, patients assigned to anamorelin (n=284) experienced a significant increase in body weight (mean 2.20 kg), compared with a mean gain of 0.14 kg among those assigned to placebo (n=141) (P<.001). Similarly, anamorelin-treated patients in ROMANA 2 (n=268) gained a mean 0.95 kg, compared with a mean loss of 0.57 kg in the placebo group (n=136), a difference that was also statistically significant (P<.001). Significant improvements in anorexia/cachexia symptoms were also observed in the anamorelin groups, compared with the placebo groups, in both ROMANA 1 (mean FAACT score 4.12 vs. 1.92; P<.001) and ROMANA 2 (3.48 vs. 1.34; P=.002). Anamorelin was associated with an improvement in fatigue in ROMANA 1 (mean FACIT-F score 0.26 vs –1.91 for placebo; P=.05), but not in ROMANA 2 (1.37 vs 1.23; P=.86).16,17
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In terms of body composition parameters, exploratory analysis demonstrated a statistically significant increase in total body mass for anamorelin vs placebo in ROMANA 1 (2.87 vs 0.07 kg; P<.001) and ROMANA 2 (2.04 vs. –0.59 kg; P<.001), as well as in fat mass in ROMANA 1 (1.21 vs. –0.13 kg; P<.001) and ROMANA 2 (0.77 vs 0.09 kg; P=.01).16,17
Anamorelin was well tolerated in both ROMANA studies. Hyperglycemia (4.8%) and diabetes mellitus (1.5%) were the most frequently observed drug-related adverse events (Table 1). Pooled survival data showed that median 1-year survival was not different between study arms, although these studies were not designed or powered to demonstrate a survival benefit.16,17 The neutral effect on patient survival was consistent with phase II studies in which the anamorelin and placebo arms showed similar survival profiles.23
Table 1. Common drug-related adverse events in the ROMANA 1 and ROMANA 2 trials16,17
| Number of Patients (%) | Number of Patients (%) | |||
| ROMANA 1 | ROMANA 2 | |||
| Anamorelin (n=323) | Placebo (n=161) | Anamorelin (n=330) | Placebo (n=161) | |
| Any drug-related TEAEs | 46 (14.4) | 15 (9.3) | 32 (9.7) | 12 (7.5) |
| Grade 1/2 | 43 (13.4) | 13 (8.1) | 22 (6.7) | 8 (5.0) |
| Grade 3/4 | 3 (0.9) | 2 (1.2) | 9 (2.7) | 4 (2.5) |
| Gastrointestinal disorders | 20 (6.3) | 3 (1.9) | 6 (1.8) | 6 (3.7) |
| Nausea | 12 (3.8) | 1 (0.6) | 5 (1.5) | 3 (1.9) |
| Metabolism and nutrition disorders | 19 (5.9) | 9 (5.6) | 21 (6.4) | 2 (1.2) |
| Diabetes mellitus, including inadequate control |
3 (0.9) | 4 (2.5) | 7 (2.1) | 0 |
| Hyperglycemia | 17 (5.3) | 5 (3.1) | 14 (4.2) | 1 (0.6) |
| Key: TEAE, treatment-emergent adverse event. | ||||
After 12 weeks, patients had the option of enrolling in an extension study (ROMANA 3) to evaluate the safety and tolerability of anamorelin. Table 2 summarizes the treatment-emergent adverse events (TEAEs) in the extension study, in which no new safety signals were identified. The ROMANA 3 data concurred with the safety profiles observed in ROMANA 1 and ROMANA 2. As in those studies, anamorelin treatment was well tolerated over 24 weeks. The only common drug-related TEAE was hyperglycemia, which was an anticipated event given anamorelin’s mode of action as a ghrelin receptor agonist.24
Table 2. Summary of treatment-emergent adverse events in ROMANA 324
| Adverse events | Number of patients (%) | |
| Anamorelin (n=323) | Placebo (n=167) | |
| One or more TEAE | ||
| All TEAEs | 179 (52.5) | 93 (55.7) |
| Chemotherapy-relateda | 93 (27.1) | 40 (24.0) |
| Drug-relateda | 12 (3.5) | 2 (1.2%) |
| Drug-related grades 3-5b | 0 (0.0) | 0 (0.0) |
| All grade 3-5 TEAEs | 77 (22.5) | 36 (21.6) |
| Any TEAE leading to drug discontinuation |
22 (6.4) | 11 (6.6%) |
| Serious TEAEs | ||
| One or more | 44 (12.8) | 21 (12.6) |
| One or more drug-related | 0 (0.0) | 0 (0.0) |
| Death | 35 (3.5) | 22 (13.2) |
| Drug-related, incidence >1% | ||
| Any drug-related TEAEs | 12 (3.5) | 2 (1.2) |
| Hyperglycemia | 4 (1.2) | 0 (0.0) |
| Key: TEAE, treatment-emergent adverse events. aInvestigator assessment, includes definitely, probably, possibly related, and unknown. bCommon Terminology Criteria for Adverse Events (CTCAE) severity: Grade 3, severe; grade 4, life-threatening or disabling; grade 5, death related to the event. |
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