Stage I-III rectal or stage II-III colon cancer with PI3K pathway alterations (adjuvant) — Karolinska Institutet (Sweden) / Scandinavian academic consortium. Funded by Swedish Research Council, Swedish Cancer Society, ALF (Stockholm County / Karolinska Institutet), Stockholm Cancer Society
Stage I-III rectal or stage II-III colon cancer with PI3K pathway alterations (adjuvant)ASCO GI 2025 LBA125 / JCO 2025
[Slide 1]
10
Key Takeaway Points
Aspirin 160 mg reduced recurrence rate by 50% in CRC patients with
tumors harboring mutations in the PI3K pathway
Can change clinical practice for around one third of patients with
non-metastasized CRC
Repurposing of safe, inexpensive, globally available drug
Importance of upfront genomic testing
ASCO Gastrointestinal
PRESENTED BY: Anna Marting Low-Dose Aspirin Reduces Recurrence Rate in Colorectal Cancer Patients with PI3K Pathway Alterations
3-Year Results from a Randomized Placebo-Controlled Trial (Abstract Number LBA125)
ASCO
AMERICAN SOCIETY OF
Cancers Symposium
#GI25
CLINICAL ONCOLOGY
Presentation is property of the author and ASCO Permission required for reuse contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 2]
4
The ALASCCA Trial (NCT02647099)
N=314
N=515 PIK3CA
ALASCCA
Randomized
exon 9/20
Group A
N=157
Aspirin 160 mg
daily for 3 years
Primary
outcome:
Time to CRC recurrence
N=157
Placebo
(TTR) in Group A
daily for 3 years
37%
Secondary
outcomes:
N=156
Disease-Free Survival
Aspirin 160 mg
daily for 3 years
(DFS) in Group A
TTR in Group B
DFS in Group B
N=156
Safety
Placebo
daily for 3 years
N=3,508 screened for
N=588
N=312
alteration in PI3K pathway:
PIK3R1/PTEN/
Randomized
Rectal cancer pTNM I-III, Colon
other PIK3CA
Group B
cancer pTNM II-III, 18-80y
April 2016:
July 2016:
July 2021:
July 2024:
Start of screening
First patient randomized
Last patient randomized
Complete 3-year follow-up
ASCO Gastrointestinal
PRESENTED BY: Anna Marting Low-Dose Aspirin Reduces Recurrence Rate in Colorectal Cancer Patients with PI3K Pathway Alterations
3-Year Results from a Randomized Placebo-Controlled Trial (Abstract Number LBA125)
ASCO
AMERICAN SOCIETY OF
#GI25
CLINICAL ONCOLOGY
Cancers Symposium
Presentation is property of the author and ASCO Permission required for reuse contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 3]
6
Primary Outcome: CRC Recurrence
Group A (PIK3CA Exons 9/20)
Group B (PIK3R1/PTEN/Other PIK3CA)
100
100
90
90
80
N (events)
3-year cum. inc. (95% CI)
80
N (events)
3-year cum. inc. (95% CI)
Aspirin 157 (12)
7.7 (4.2 12.5)
Aspirin 156 (12)
7.7 (4.2 12.6)
70
70
Placebo 157 (23)
14.1 (9.2 20.0)
Placebo 156 (27)
16.8 (11.4 23.1)
60
60
50
Hazard ratio (95% CI)
0.49 (0.24 - 0.98)
50
Hazard ratio (95% CI)
0.42 (0.21 - 0.83)
p-value
0.044
p-value
0.013
40
40
30
30
20
Placebo
20
Placebo
10
10
0
Aspirin 160 mg
0
Aspirin 160 mg
0
6
12
18
24
30
36
0
6
12
18
24
30
36
Months from randomization
Months from randomization
ASCO Gastrointestinal
PRESENTED BY: Anna Marting Low-Dose Aspirin Reduces Recurrence Rate in Colorectal Cancer Patients with PI3K Pathway Alterations
#GI25
ASCO
AMERICAN SOCIETY OF
3-Year Results from a Randomized Piacebo-Controlled Trial (Abstract Number LBA125)
CLINICAL ONCOLOGY
Cancers Symposium
Presentation is property of the author and ASCO Permission required for reuse contact
KNOWLEDGE CONQUERS CANCER
---
[Slide 4]
4
The ALASCCA Trial (NCT02647099)
N=314
N=515 PIK3CA
ALASCCA
Randomized
exon 9/20
Adjuvant ASA vid
Group A
N=157
TITTIT
Aspirin 160 mg
daily for 3 years
Primary
outcome:
Time to CRC recurrence
N=157
Placebo
(TTR) in Group A
daily for 3 years
37%
Secondary
outcomes:
N=156
Disease-Free Survival
Aspirin 160 mg
daily for 3 years
(DFS) in Group A
TTR in Group B
DFS in Group B
N=156
Safety
Placebo
daily for 3 years
N=3,508 screened for
N=588
N=312
alteration in PI3K pathway:
PIK3R1/PTEN/
Randomized
Rectal cancer pTNM I-III, Colon
other PIK3CA
Group B
cancer pTNM II-III, 18-80y
April 2016:
July 2016:
July 2021:
July 2024:
Start of screening
First patient randomized
Last patient randomized
Complete 3-year follow-up
ASCO Gastrointestinal
PRESENTED BY: Anna Marting: Low-Dose Aspirin Reduces Recurrence Rate in Colorectal Cancer Patients with PI3K Pathway Alterations
ASCO
AMERICAN SOCIETY OF
#GI25
3-Year Results from a Randomized Placebo-Controlled Trial (Abstract Number: LBA125)
CLINICAL ONCOLOGY
Cancers Symposium
Presentation is property of the author and ASCO Permission required for reuse; contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 5]
5
Patient Characteristics
626 patients randomized
Median age 66 years
(range 31-80)
Stage
Stage
pTNM Stage in colon
III
II
cancer patients
47%
53%
52% Females
Stage I
24%
67% Colon cancer
pTNM Stage in rectal
Stage II
Stage III
33% Rectal cancer
cancer patients
40%
36%
50% of rectal cancer patients
50% of colon cancer patients
given neoadjuvant therapy
given adjuvant therapy
ASCO Gastrointestinal
PRESENTED BY: Anna Marting Low-Dose Aspirin Reduces Recurrence Rate in Colorectal Cancer Patients with PI3K Pathway Atterations
#GI25
3-Year Results from a Randomized Placebo- Controlled Trial (Abstract Number LBA125)
ASCO
AMERICAN SOCIETY OF
CLINICAL ONCOLOGY
Cancers Symposium
Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 6]
6
Primary Outcome: CRC Recurrence
Group A (PIK3CA Exons 9/20)
Group B (PIK3R1/PTEN/Other PIK3CA)
100
100
90
90
80
N (events)
3-year cum. inc. (95% CI)
80
N (events)
3-year cum. inc. (95% CI)
Aspirin
157 (12)
7.7 (4.2 12.5)
Aspirin
156 (12)
7.7 (4.2 12.6)
Cumulative Incidence of
70
70
CRC Recurrence (%)
Placebo 157 (23)
14.1 (9.2 20.0)
60
Hazard ratio (95% CI)
0.49 (0.24 - 0.98)
p-value
Cumulative Incidence of
CRC Recurrence (%)
Placebo 156 (27)
16.8 (11.4 23.1)
60
50
50
Hazard ratio (95% CI) 0.42 (0.21 - 0.83)
0.044
p-value
0.013
40
40
30
30
20
Placebo
20
Placebo
10
+++
10
0
Aspirin 160 mg
0
Aspirin 160 mg
0
6
12
18
24
30
36
0
6
12
18
24
30
36
Months from randomization
Months from randomization
ASCO Gastrointestinal
PRESENTED BY: Anna Marting Low-Dose Aspirin Reduces Recurrence Rate in Colorectal Cancer Patients with PI3K Pathway Alterations
#GI25
ASCO
AMERICAN SOCIETY OF
3-Year Results from a Randomized Placebo-Controlled Trial (Abstract Number LBA125)
CLINICAL ONCOLOGY
Cancers Symposium
Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
---
[Slide 7]
10
Key Takeaway Points
VAVA
Aspirin 160 mg reduced recurrence rate by 50% in CRC patients with
tumors harboring mutations in the PI3K pathway
Can change clinical practice for around one third of patients with
non-metastasized CRC
Repurposing of safe, inexpensive, globally available drug
Importance of upfront genomic testing
ASCO Gastrointestinal
PRESENTED BY: Anna Marting: Low-Dose Aspirin Reduces Recurrence Rate in Colorectal Cancer Patients with PI3K Pathway Alterations
3-Year Results from a Randomized Placebo-Controlled Trial (Abstract Number: LBA125)
ASCO
AMERICAN SOCIETY OF
#GI25
CLINICAL ONCOLOGY
Cancers Symposium
Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org
KNOWLEDGE CONQUERS CANCER
ALASCCA is the first biomarker-driven randomized trial showing daily aspirin prevents recurrence in PI3K pathway-altered CRC. Both Group A (PIK3CA exon 9/20) and Group B (PIK3R1/PTEN/other PIK3CA) met primary/secondary endpoints with 51-58% recurrence reduction. Expands the targetable population beyond classical PIK3CA mutations. NCCN Guidelines updated post-ASCO GI 2025. Will require upfront molecular profiling of early-stage CRC — a new clinical workflow. Repurposing of a cheap, globally available agent.
DFS: Group A HR 0.61 (95% CI 0.34-1.08, P=0.091) — not statistically significant; 3-year DFS 88.5% aspirin vs. 81.4% placebo. Group B HR 0.51 (95% CI 0.29-0.88, P=0.017) — SIGNIFICANT; 3-year DFS 89.1% vs. 78.7%. OS data still maturing. Findings expected to change clinical practice for ~1/3 of early-stage CRC patients.
Key AEs: 3 aspirin-related serious AEs total: 1 GI bleeding, 1 hematoma, 1 allergic reaction. Excellent safety profile: only 3 severe aspirin-related AEs in ~313 patients on aspirin. No treatment-related deaths. Aspirin is inexpensive, globally available, safe in most patients.
✅ Practice-changing: NCCN Guidelines now recommend aspirin for PIK3CA-mutated CRC. ALASCCA is the first biomarker-driven randomized trial showing daily aspirin prevents recurrence in PI3K pathway-altered CRC. Both Group A (PIK3CA exon 9/20) and Group B (PIK3R1/PTEN/other PIK3CA) met primary/secondary endpoints with 51-58% recurrence reduction. Expands the targetable population beyond classical PIK3CA mutations. NCCN Guidelines updated post-ASCO GI 2025. Will require upfront molecular profiling of early-stage CRC — a new clinical workflow. Repurposing of a cheap, globally available agent.
