trialsTrialNegative

ADIUVO

aka ADIUVO trial

ADIUVO asked whether people whose low-grade adrenal cancer had been fully removed should take the toxic drug mitotane for two years to prevent recurrence; recurrence and survival were no different from watching and waiting, so observation with regular scans is the standard for this group.

ADIUVO was an international open-label randomised phase 3 trial with a parallel observational study, run by the University of Turin with the ENSAT network, in patients with completely resected adrenocortical carcinoma at low to intermediate risk of recurrence. Patients were randomised to adjuvant mitotane for at least two years or active surveillance; the primary endpoint was recurrence-free survival. Slow recruitment closed the trial after 91 randomised patients.

Five-year recurrence-free survival was 79 percent with mitotane against 75 percent with surveillance (hazard ratio 0.74, not significant) and five-year overall survival 95 against 86 percent with two and five deaths respectively; every patient on mitotane had adverse events and 19 percent stopped treatment. The corpus's localised adrenocortical carcinoma page cites ADIUVO for observation rather than mitotane in low-risk disease, and ADIUVO-2 now tests intensified adjuvant treatment in high-risk disease.

Setting

Completely resected adrenocortical carcinoma at low to intermediate risk of recurrence (stage I to III, R0, Ki67 10 percent or less) at 23 centres in seven countries: adjuvant mitotane for at least two years against surveillance, with recurrence-free survival as the primary endpoint

Phase

Phase 3

Sponsor

University of Turin, Italy

Registry

NCT00777244

Headline result

Five-year recurrence-free survival 79 percent with adjuvant mitotane against 75 percent with surveillance (hazard ratio 0.74, 95% CI 0.30 to 1.85); overall survival not significantly different; adverse events in every mitotane patient.

Reported

2023

Enrolled

91 randomisedThe registry gives an estimated 200 and was never updated; the Lancet Diabetes and Endocrinology report randomised 91 patients (45 mitotane, 46 surveillance) between 2008 and 2018 before the trial closed for slow recruitment, alongside an observational cohort of 95.

Outcomes

3top

In plain words

What these results mean for people, not percentages

91 randomised

Recurrence-free survival at 5 yearsprimarysurrogate endpoint

79 vs 75 out of 100 alive without the cancer coming back at 5 years with Adjuvant mitotane compared with Surveillance; 4 more per 100.
Roughly one extra person helped for every 25 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
Put another way, the treated group had about 26 percent lower chance of the event at any given time (hazard ratio 0.74, likely range 0.3 to 1.85).

The likely range for the hazard ratio crosses 1, so the difference could be due to chance.
This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.

Overall survival at 5 yearssurvival endpoint

95 vs 86 out of 100 alive at 5 years with Adjuvant mitotane compared with Surveillance; 9 more per 100.
Roughly one extra person helped for every 11 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.

Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.

Discontinuation of mitotane for adverse eventsother endpoint

19 out of 100 people reached this endpoint with Adjuvant mitotane.

There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.

Caveats

These results apply to the people the trial enrolled: Completely resected adrenocortical carcinoma at low to intermediate risk of recurrence (stage I to III, R0, Ki67 10 percent or less) at 23 centres in seven countries: adjuvant mitotane for at least two years against surveillance, with recurrence-free survival as the primary endpoint. People in a different situation may not see the same effect.
Only 91 people took part, so the numbers are less certain than in a large trial.

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.

91 randomised.

Recurrence-free survival at 5 yearsprimary

HR 0.74 (0.3 to 1.85)

Adjuvant mitotane79 of 100

n = 45

Surveillance75 of 100

n = 46

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95% CI 67 to 94 · 95% CI 63 to 90

Source

Overall survival at 5 years

Adjuvant mitotane95 of 100

n = 45

Surveillance86 of 100

n = 46

Download

95% CI 89 to 100; 2 deaths · 95% CI 74 to 100; 5 deaths

Source

Discontinuation of mitotane for adverse events

Adjuvant mitotane19 of 100

n = 42

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All 42 treated patients had adverse events; no grade 4 events

Source

Endpoint	Arm	n	Value	HR (95% CI)	p	Source
Recurrence-free survival at 5 yearsprimary	Adjuvant mitotane	45	79%	0.74 (0.3 to 1.85)	-	link
Recurrence-free survival at 5 yearsprimary	Surveillance	46	75%	0.74 (0.3 to 1.85)	-	link
Overall survival at 5 years	Adjuvant mitotane	45	95%	-	-	link
Overall survival at 5 years	Surveillance	46	86%	-	-	link
Discontinuation of mitotane for adverse events	Adjuvant mitotane	42	19%	-	-	link