SARC041
Abemaciclib versus placebo in advanced dedifferentiated liposarcoma. A phase 3 randomized, double-blind trial.
Background and design
SARC041 was an investigator-initiated phase 3 randomized, double-blind trial sponsored by the Sarcoma Alliance for Research through Collaboration (SARC). It tested abemaciclib, an oral CDK4/6 inhibitor, against placebo in patients with advanced dedifferentiated liposarcoma, a sarcoma subtype marked by near-universal high-level CDK4 amplification. Enrollment was conducted in the United States. Patients who progressed on placebo could cross over to open-label abemaciclib.
Key eligibility
- Age 18 years or older
- ECOG performance status 0 to 1
- Recurrent or metastatic dedifferentiated liposarcoma (purely well-differentiated disease excluded)
- Disease progression by RECIST 1.1 within the 6 months before study entry
- Any number of prior therapies, including none
- Excluded: extensive disease needing immediate treatment
Randomization
Patients were randomized 1:1, stratified by prior systemic treatment (0 versus 1 or more lines).
Imaging by CT every 6 weeks for 36 weeks, then every 12 weeks.
End points
Statistical plan
The target sample size was 108 evaluable patients (54 per arm), providing 80% power to detect a hazard ratio of 0.6 for PFS. The design assumed a median PFS of 3.3 months in the placebo arm; a hazard ratio of 0.6 corresponded to a median PFS of 5.4 months in the abemaciclib arm.
Baseline characteristics
| Characteristic | Placebo (N = 54) | Abemaciclib (N = 54) |
|---|---|---|
| Sex | ||
| Female | 25 (46%) | 17 (31%) |
| Male | 29 (54%) | 37 (69%) |
| Tumor location at diagnosis | ||
| Abdomen / retroperitoneum | 43 (80%) | 49 (92%) |
| Chest | 4 (7.5%) | 1 (1.9%) |
| Lower extremity | 7 (13%) | 3 (5.7%) |
| Spine | 0 (0%) | 1 (1.9%) |
| Age at enrollment | ||
| Median (range) | 67 (41 to 84) | 67 (19 to 84) |
| Prior lines of therapy | ||
| 0 | 28 (52%) | 27 (50%) |
| 1 or more | 26 (48%) | 27 (50%) |
Primary end point: progression-free survival
Stratified log-rank P less than 0.001.
| Landmark PFS | Abemaciclib | Placebo |
|---|---|---|
| 6-month PFS | 60% | 22% |
| 12-month PFS | 39% | 13% |
Objective response rate
Response measured by RECIST percent change from baseline. Confidence intervals and odds ratio for ORR were not reported in the source.
PFS after crossover
Of placebo-arm patients, 46 (85%) received abemaciclib after progression.
Overall survival
Stratified log-rank P equals 0.07. OS was assessed despite 85% crossover from placebo to abemaciclib.
| Landmark OS | Abemaciclib | Placebo |
|---|---|---|
| 12-month OS | 85% | 71% |
| 24-month OS | 72% | 51% |
Exploratory: PFS by prior therapy (abemaciclib arm)
Among patients receiving abemaciclib, those with no prior lines of therapy had longer median PFS than those with one or more prior lines. This forest-style comparison uses the only two subgroups and the at-risk counts reported in the source.
Log-rank P equals 0.029. Bars are scaled to median PFS; a per-subgroup hazard ratio and confidence interval were not reported. The two n values (27 and 27) are the at-risk counts at time zero shown in the source figure.
Tolerability overview
The source reported selected adverse events by grade and dose-reduction rates. A summary of any-grade AEs, overall grade 3 or higher AEs, treatment-related versus all-cause attribution, and fatal events was not presented in the source.
Key adverse events by grade
Values are percentages. The source did not separate treatment-related from all-cause events.
| Adverse event | Placebo | Abemaciclib | ||||
|---|---|---|---|---|---|---|
| G2 | G3 | G4 | G2 | G3 | G4 | |
| Hematologic | ||||||
| Anemia | 2 | — | — | 22 | 4 | — |
| Lymphocyte count decreased | 2 | — | — | 7 | — | 2 |
| Neutrophil count decreased | 2 | — | — | 9 | 11 | 2 |
| Platelet count decreased | — | — | — | — | 4 | — |
| White blood cell decreased | — | — | — | 13 | 7 | — |
| Gastrointestinal and other | ||||||
| Abdominal pain or fullness | 6 | 4 | — | 4 | 2 | — |
| Diarrhea | 2 | — | — | 28 | 7 | — |
| Creatinine increased | 4 | 2 | — | 20 | 6 | — |
Events at 20% or higher in either arm (any reported grade)
Bars sum the grade 2 to 4 percentages reported for each event. Diarrhea, anemia, and creatinine increased reached the 20% threshold in the abemaciclib arm; no listed event reached 20% with placebo.
Per-event totals are the sum of reported grade 2 to 4 values: diarrhea 28 plus 7 equals 35; anemia 22 plus 4 equals 26; creatinine increased 20 plus 6 equals 26. Grade 1 events were not reported, so true any-grade rates may be higher.
References
- Dickson MA, Ballman KV, Weiss M, et al. SARC041: a phase 3 randomized double-blind study of abemaciclib versus placebo in patients with advanced dedifferentiated liposarcoma. Presented at: 2026 ASCO Annual Meeting (Plenary Session); May 29 to June 2, 2026; Chicago, IL.
- SARC041: study of abemaciclib versus placebo in patients with advanced dedifferentiated liposarcoma. ClinicalTrials.gov identifier: NCT04967521.
No peer-reviewed journal publication was available at the time this QuickView was prepared. All efficacy and safety values are drawn from the ASCO 2026 presentation and should be confirmed against the full publication when released.
Abbreviations
- AE
- adverse event
- CDK4/6
- cyclin-dependent kinase 4 and 6
- CI
- confidence interval
- CT
- computed tomography
- CTCAE
- Common Terminology Criteria for Adverse Events
- DDLS
- dedifferentiated liposarcoma
- ECOG PS
- Eastern Cooperative Oncology Group performance status
- HR
- hazard ratio
- mPFS
- median progression-free survival
- NR
- not reached
- ORR
- objective response rate
- OS
- overall survival
- PFS
- progression-free survival
- PO bid
- orally twice daily
- RECIST
- Response Evaluation Criteria in Solid Tumors
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