ALASCCA: trial | Bending the Curve: Trial by Trial

ALASCCA

Needs review

Adjuvant Low Dose Aspirin in Colorectal Cancer (ALASCCA): low-dose aspirin for PI3K-altered localized colorectal cancer

Population

Patients with stage I, II or III rectal cancer or stage II or III colon cancer with PI3K-pathway alterations: alterations were detected in 1103 of 2980 patients (37.0%) with complete genomic data (515 with group A and 588 with group B alterations). The abstract states that 314 and 312 patients, respectively, were assigned to aspirin or placebo (total 626, equal to the registry's actual enrolment); it does not give arm sizes.

Design

Double-blind, randomised, placebo-controlled trial of aspirin 160 mg or matched placebo once daily for 3 years (1:1) in patients with somatic alterations in PI3K pathway genes. Group A: prespecified PIK3CA hotspot mutations in exon 9 or 20; group B: other moderate- or high-impact somatic variants in PIK3CA, PIK3R1 or PTEN. Primary endpoint colorectal cancer recurrence (time-to-event analysis) in group A; secondary endpoints included recurrence in group B, disease-free survival and safety. ClinicalTrials.gov lists phase 3 and 626 actual enrolment.

Primary endpoint

Time to recurrence

Arms

Placebo (control): Matched placebo once daily for 3 years
Aspirin 160 mg (experimental): Aspirin 160 mg once daily for 3 years

People

Martling A

3-year recurrence rateHR 0.49 (95% CI 0.24–0.98)Δ 3-year recurrence rate−6.4 points3-year recurrence rateHR 0.42 (95% CI 0.21–0.83)Δ 3-year recurrence rate−9.1 pointsDFSHR 0.61 (95% CI 0.34–1.08)Δ 36-month DFS+7.1 points

Show the numbers

Results reported for ALASCCA
Endpoint	Analysis	Aspirin 160 mg	Placebo	Effect
3-year recurrence rateGroup A: patients with PIK3CA hotspot mutations in exon 9 or 20 (primary-endpoint population)	primaryMartling 2025	7.7%	14.1%	HR 0.49 (95% CI 0.24–0.98)P=0.04Estimated 3-year cumulative incidence of recurrence, as published. Primary endpoint.
3-year recurrence rateGroup B: patients with other moderate- or high-impact variants in PIK3CA, PIK3R1 or PTEN	primaryMartling 2025	7.7%	16.8%	HR 0.42 (95% CI 0.21–0.83)Secondary endpoint; no P value is given in the abstract.
DFSGroup A: patients with PIK3CA hotspot mutations in exon 9 or 20	primaryMartling 2025	88.5% at 3 y	81.4% at 3 y	HR 0.61 (95% CI 0.34–1.08)Secondary endpoint; the confidence interval includes 1.
DFSGroup B: patients with other moderate- or high-impact variants in PIK3CA, PIK3R1 or PTEN	primaryMartling 2025	89.1% at 3 y	78.7% at 3 y	HR 0.51 (95% CI 0.29–0.88)Secondary endpoint.

Results reported for ALASCCA
Endpoint	Analysis	Aspirin 160 mg	Placebo	Effect
3-year recurrence rateGroup A: patients with PIK3CA hotspot mutations in exon 9 or 20 (primary-endpoint population)	primaryMartling 2025	7.7%	14.1%	HR 0.49 (95% CI 0.24–0.98)P=0.04Estimated 3-year cumulative incidence of recurrence, as published. Primary endpoint.
3-year recurrence rateGroup B: patients with other moderate- or high-impact variants in PIK3CA, PIK3R1 or PTEN	primaryMartling 2025	7.7%	16.8%	HR 0.42 (95% CI 0.21–0.83)Secondary endpoint; no P value is given in the abstract.
DFSGroup A: patients with PIK3CA hotspot mutations in exon 9 or 20	primaryMartling 2025	88.5% at 3 y	81.4% at 3 y	HR 0.61 (95% CI 0.34–1.08)Secondary endpoint; the confidence interval includes 1.
DFSGroup B: patients with other moderate- or high-impact variants in PIK3CA, PIK3R1 or PTEN	primaryMartling 2025	89.1% at 3 y	78.7% at 3 y	HR 0.51 (95% CI 0.29–0.88)Secondary endpoint.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
3-year recurrence rate	0.49	0.24–0.98
3-year recurrence rate	0.42	0.21–0.83
DFS	0.61	0.34–1.08
DFS	0.51	0.29–0.88

Appears in

2025 Adjuvant aspirin: ASCOLT and ALASCCA (PI3K-altered tumours)

Sources

Martling A, Hed Myrberg I, Nilbert M, Grönberg H, Granath F, Eklund M, et al. Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer. N Engl J Med. 2025;393(11):1051-1064.
PubMed DOI