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

Abstract

Background: Cancer 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 methods: ROMANA 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).

Results: Of 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.

Conclusion: During 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 numbers: ROMANA 1 (NCT01387269), ROMANA 2 (NCT01387282), and ROMANA 3 (NCT01395914).

Keywords: ROMANA 1 and ROMANA 2; ROMANA 3; anamorelin; anorexia–cachexia symptoms; body weight; non-small-cell lung cancer.

© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Figures

Figure 1

CONSORT diagram of ROMANA 3. aPatients enrolled in ROMANA 3 stayed on their initial treatment arm (from ROMANA 1 or ROMANA 2). bNo deaths were drug related. cIncluding the patients who did not receive study drug. Patients completing the study are defined as patients finalizing the week 12/day 85 visit. AE, adverse event; ITT, intent-to-treat.

Figure 2

Least-squares mean change (±SE) from baseline of original trials in (A) body weight and (B) FAACT Anorexia/Cachexia Subscale Domain Score during 24 weeks of treatment in patients enrolled in ROMANA 3. ITT population. aThe P value indicates a significant difference in body weight or FAACT Anorexia/Cachexia Subscale Domain Score between anamorelin- and placebo-treated patients from baseline of ROMANA 1 and ROMANA 2 to each visit throughout the 0–24w treatment period and completion of extension trial (ROMANA 3) as part of the post-hoc analysis. A/CS, Anorexia/Cachexia Subscale; ANAM, anamorelin HCl; FAACT, Functional Assessment of Anorexia/Cachexia Treatment; ITT, intent-to-treat; SE, standard error.