PIONEER

22 evidence topics · 4 sources

Objective

Comparator trial objective

“efficacy and safety of avapritinib versus placebo” (opens the source at this quote in a new tab)

Location and study date

Long-term follow-up: data cutoff

“February 21, 2025” (opens the source at this quote in a new tab)

Study design

Randomized comparison: masking and control

“randomized, double-blind, placebo-controlled” (opens the source at this quote in a new tab)

Long-term extension design

“open-label part 3 is ongoing with up to 5 years of follow-up.” (opens the source at this quote in a new tab)

Eligibility criteria

Symptom severity at enrollment

“moderate to severe ISM” (opens the source at this quote in a new tab)

Minimum baseline total symptom score

Eligibility measure	Threshold
TSS	“≥28”

Treatment

Avapritinib dose for ISM

“The recommended dosage of AYVAKIT is 25 mg orally once daily in patients with ISM.” (opens the source at this quote in a new tab)

Background treatment in both groups

“best supportive care” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using ISM-SAF total symptom score as the primary endpoint

Primary endpoint: symptom assessment and averaging period

“14-day average of patient-reported severity of 11 symptoms” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Randomized analysis: treatment-group counts

Group	Participants
Avapritinib	“n=141”
Placebo	“n=71”

Description of analysis sets

FDA label analysis: missing continuous symptom-score observations

“Markov chain Monte Carlo simulation was used to impute the missing values at Baseline or C7D1.” (opens the source at this quote in a new tab)

Results

Participant disposition

Long-term analysis across PIONEER study parts

“226 patients initiated avapritinib at 25 mg QD.” (opens the source at this quote in a new tab)

Baseline characteristics

Avapritinib group: baseline characteristics in the FDA label

Characteristic	Value
Median age, years	“50”
Female, percent	“71%”
Mean TSS	“50.17”

Efficacy results

Comparator avapritinib, PIONEER trial: week 24 total symptom score, avapritinib

“a decrease of 15.6 points (95% CI, −18.6 to −12.6)” (opens the source at this quote in a new tab)

Comparator avapritinib, PIONEER trial: week 24 total symptom score, placebo

“a decrease of 9.2 points (−13.1 to −5.2)” (opens the source at this quote in a new tab)

Comparator avapritinib, PIONEER trial: abstract-reported statistical significance

“From baseline to week 24, avapritinib-treated patients had a decrease of 15.6 points (95% CI, −18.6 to −12.6) in TSS compared to a decrease of 9.2 points (−13.1 to −5.2) in the placebo group; P<0.003.” (opens the source at this quote in a new tab)

FDA label analysis: week 24 absolute mean TSS change

Avapritinib plus BSC	Placebo plus BSC	Two-sided p-value
“-15.33”	“-9.64”	“0.012”

Health-related quality of life and patient-reported outcomes

PIONEER Part 2: MC-QoL at cycle 7, day 1

Measure	Avapritinib plus BSC	Placebo plus BSC
Mean change from baseline	“−19.2”	“−9.55”

Safety results

PIONEER Part 2: edema events

Measure	Avapritinib plus BSC	Placebo plus BSC
Participants with at least one edema adverse event	“25.5%”	“11.3%”

PIONEER Part 2: anaphylaxis treated with epinephrine after baseline

Avapritinib plus BSC	Placebo plus BSC
“2”	“3”

Comparator avapritinib, PIONEER long-term follow-up

“Serious TRAEs occurred in 3 patients (1%), and 7 patients (3%) discontinued treatment because of TRAEs.” (opens the source at this quote in a new tab)

Study limitations

Summary

PIONEER evaluates avapritinib, not bezuclastinib, in moderate-to-severe ISM. Its results do not provide a head-to-head comparison of the two drugs. The publication and FDA label report different numerical TSS analyses, which are preserved separately. Long-term Part 3 is open-label. The Canadian appraisal reports only two versus three post-baseline anaphylaxis events treated with epinephrine, limiting the precision of conclusions about that outcome.