ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia

Abstract

BackgroundCancer anorexia–cachexia is a debilitating condition frequently observed in NSCLC patients, characterized by decreased body weight, reduced food intake, and impaired quality of life. Anamorelin, a novel selective ghrelin receptor agonist, has anabolic and appetite-enhancing activities.Patients and methodsROMANA 3 was a safety extension study of two phase 3, double-blind studies that assessed safety and efficacy of anamorelin in advanced NSCLC patients with cachexia. Patients with preserved Eastern Cooperative Oncology Group ≤2 after completing 12 weeks (w) on the ROMANA 1 or ROMANA 2 trials (0–12 weeks) could enroll in ROMANA 3 and continue to receive anamorelin 100 mg or placebo once daily for an additional 12w (12–24 weeks). The primary endpoint of ROMANA 3 was anamorelin safety/tolerability (12–24 weeks). Secondary endpoints included changes in body weight, handgrip strength (HGS), and symptom burden (0–24 weeks).ResultsOf the 703 patients who completed ROMANA 1 and ROMANA 2, 513 patients entered ROMANA 3 (anamorelin, N = 345, mean age 62.0 years; placebo, N = 168; mean age 62.2 years). During ROMANA 3, anamorelin and placebo groups had similar incidences of treatment–emergent adverse events (TEAEs; 52.2% versus 55.7%), grade ≥3 TEAEs (22.4% versus 21.6%), and serious TEAEs (12.8% versus 12.6%). There were 36 (10.5%) and 23 (13.8%) deaths in the anamorelin and placebo groups, respectively; none were drug-related. Improvements in body weight and anorexia–cachexia symptoms observed in the original trials were consistently maintained over 12–24 weeks. Anamorelin, versus placebo, significantly increased body weight from baseline of original trials at all time points (P < 0.0001) and improved anorexia–cachexia symptoms at weeks 3, 6, 9, 12, and 16 (P < 0.05). No significant improvement in HGS was seen in either group.ConclusionDuring the 12–24 weeks ROMANA 3 trial, anamorelin continued to be well tolerated. Over the entire 0–24w treatment period, body weight and symptom burden were improved with anamorelin.Clinical trial registration numbersROMANA 1 (NCT01387269), ROMANA 2 (NCT01387282), and ROMANA 3 (NCT01395914).

Cancer cachexia: Are we ready to take a step forward?

“…The rates of hyperglycemia and diabetes noted in the anamorelin group versus the control group were low across all trials. In addition, an extension study of ROMANA 3 for patients from the ROMANA 1 and 2 trials who continued on therapy demonstrated ongoing safety and efficacy from week 12 to week 24 …”

“…In addition, an extension study of ROMANA 3 for patients from the ROMANA 1 and 2 trials who continued on therapy demonstrated ongoing safety and efficacy from week 12 to week 24. 9 As a discussant of the ROMANA data presentation at the Chicago multidisciplinary lung cancer meeting, 10 I asked the audience the following question: "If you had a drug that improved appetite, body weight and lean body mass, with minimal toxicity, would you prescribe it for patients with cancer cachexia?" The answer was overwhelmingly yes.…”

Growth hormone secretagogues: history, mechanism of action, and clinical development

“…Subsequently, an extension study, ROMANA3 (NCT01395914), enrolling 513 patients with NSCLC from ROMANA1 and ROMANA2, evaluated the efficacy and safety of anamorelin for an additional 12 weeks. As with prior studies, anamorelin was associated with a favourable safety profile and increased body weight but not muscle strength . Anamorelin has shown similar results in a clinical trial enrolling patients with NSCLC‐induced cachexia in Japan [Clinical trial registration: JapicCTI‐111415 (Japan Pharmaceutical Information Center Clinical Trials Information)] .…”

A multi‐targeted treatment approach to cancer cachexia: Auckland's Cancer Cachexia evaluating Resistance Training (ACCeRT) trial

“…This is in contrast to the results of another pre‐cachexia/cachexia population study investigating anamorelin within the ROMANA 1 and 2 studies. Results showed a mean weight gain +2.2 kg in the treatment arm compared with +0.14 kg in the placebo arm (ROMANA 1) and +0.95 kg in the treatment arm compared with −0.57 kg in the placebo arm (ROMANA 2), all at 12 weeks, with +3.1 kg in the treatment arm compared with +0.9 kg in the placebo arm at 24 weeks (ROMANA 3) …”

“…During this time, there has been a change in the consideration of cachexia from a ‘very late change’ and inescapable event to ‘an early phenomenon’ with signs of cachexia present upon primary cancer diagnosis even if weight loss has not yet occurred. This has led to the recent shift in developing effective treatments aimed at preventing rather than reversing the symptoms, as seen in the earlier studies …”