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trialsTrialMixed

ROMANA 1 and ROMANA 2

ROMANA 1 and 2 were two phase 3 trials of an appetite-hormone mimic in lung cancer patients with wasting. Patients gained muscle but not grip strength, which split regulators: approved in Japan, rejected in Europe.

ROMANA 1 (n=484) and ROMANA 2 (n=495) were identical double-blind trials with co-primary endpoints of lean body mass (DXA) and handgrip strength over 12 weeks. Lean body mass increased with anamorelin (ROMANA 1: +0.99 kg vs -0.47 kg; ROMANA 2: +0.65 kg vs -0.98 kg), and body weight, appetite and anorexia-cachexia symptom scores improved, but handgrip strength did not differ from placebo in either trial. Hyperglycaemia and nausea were the main adverse events. The EMA refused marketing authorisation in 2017 citing the absence of a functional benefit; Japan approved anamorelin (Adlumiz) in 2021 for NSCLC, gastric, pancreatic and colorectal cancer cachexia. ROMANA established that lean mass can be pharmacologically increased in cachexia, and that regulators want function or survival, which shaped the endpoint strategy for GDF-15 antagonists.

Setting
Unresectable stage III/IV NSCLC with cachexia (weight loss over 5% in 6 months or BMI under 20): anamorelin 100 mg/day vs placebo for 12 weeks
Phase
Phase 3
Sponsor
Helsinn Therapeutics
Registry
Headline result
Lean body mass increased (about +1 to +1.5 kg vs placebo); handgrip strength unchanged.
Reported
2016
Enrolled
979
Replication
Japanese phase 2/3 trials (ONO-7643) in NSCLC and GI cancers reproduced the lean mass effect; the ROMANA 3 extension confirmed safety over 24 weeks.

Outcomes

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In plain words
What these results mean for people, not percentages
979 people took part
Change in lean body mass over 12 weeks (ROMANA 1)primaryother endpoint
  • Anamorelin: 1 kg; Placebo: -0.5 kg.
Change in lean body mass over 12 weeks (ROMANA 2)primaryother endpoint
  • Anamorelin: 0.7 kg; Placebo: -1 kg.
Be careful
  • The p-value (<0.0001) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
  • This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
  • These results apply to the people the trial enrolled: Unresectable stage III/IV NSCLC with cachexia (weight loss over 5% in 6 months or BMI under 20): anamorelin 100 mg/day vs placebo for 12 weeks. People in a different situation may not see the same effect.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

979 participants enrolled.

Change in lean body mass over 12 weeks (ROMANA 1)primary
· p <0.0001
Anamorelin
0.99 mo
Placebo
-0.47 mo
Source
Change in lean body mass over 12 weeks (ROMANA 2)primary
· p <0.0001
Anamorelin
0.65 mo
Placebo
-0.98 mo
Source
EndpointArmnValueHR (95% CI)pSource
Change in lean body mass over 12 weeks (ROMANA 1)primaryAnamorelin3230.99 kg<0.0001link
Placebo161-0.47 kg
Change in lean body mass over 12 weeks (ROMANA 2)primaryAnamorelin3300.65 kg<0.0001link
Placebo165-0.98 kg
Replication
Japanese phase 2/3 trials (ONO-7643) in NSCLC and GI cancers reproduced the lean mass effect; the ROMANA 3 extension confirmed safety over 24 weeks.

Connected

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