Abstract
Purpose
We assessed the benefit of adjuvant aspirin in resected PIK3CA-mutated colon cancer patients.
Patients & Methods
This was a phase III, prospective, randomized, placebo-controlled, double-blind, multicenter, and multinational trial. Patients with resected colon cancer stage II and III harbouring an activating PIK3CA mutation were included. Due to financial constraints, the trial was prematurely closed. Randomization was 2:1 to aspirin 100mg versus placebo daily for 3 years. The primary endpoint was disease-free survival (DFS). Secondary endpoints included the time to disease recurrence (TTR), overall survival, and adverse events (AE).
Results
Overall, 1,040 patients were screened for PIK3CA mutations, with 112 randomized to aspirin (N=74) and placebo (N=38). Median age was 66 years and 42.9% were female. After a median follow-up of 4 years, 19 DFS events occurred, including 10 in the aspirin and nine in the placebo arm. The HR for DFS was 0.57 (90%CI: 0.27-1.22), in favor of aspirin (p=0.11). DFS rates at 5 years were 86.5% (90%CI: 77.7%-92.0%) in the aspirin and 72.9% (90%CI: 55.7%-84.3%) in the placebo arm. The HR for TTR was 0.49 (90%CI: 0.21-1.19, p=0.089) in favor of aspirin. No patient experienced aspirin-related serious AEs.
Conclusions
The SAKK 41/13 is the first randomized trial to provide clinical evidence of a protective effect of adjuvant aspirin in resected PIK3CA-mutant colon cancer patients, with clinically relevant DFS and TTR improvements. Although results were not statistically significant due to premature study closure, adjuvant aspirin warrants individual consideration in patients with resected PIK3CA-mutant colon cancer stage II and III.
Trial registration
ClinicalTrials.gov Identifier: NCT02467582
Keywords: aspirin, cancer, colon cancer, adjuvent treatment, PIK3CA mutations
Introduction
Colorectal cancer is the third most common malignancy for both women and men and is responsible for almost 10% of all cancer deaths [1]. Particularly, the dramatic rise in the incidence of colorectal cancer in the 3rd, 4th and 5th decade is concerning [2]. Hence, colorectal cancer represents a tremendous public health problem. Patients with non-metastatic colorectal cancer undergo oncologic resection including en bloc lymphadenectomy as a current standard. Stage III (node-positive) colorectal cancer patients generally receive adjuvant chemotherapy, while stage II patients may undergo adjuvant chemotherapy if high risk features are present such as T4 stage or lymphovascular invasion [3]. Despite complete surgical removal and adjuvant chemotherapy, up to 25% of stage II patients [4] and up to 50% of stage III patients will suffer from disease recurrence [5], which is associated with poor prognosis. This remains an unsettling problem for surgical and medical oncologists. Tremendous efforts have been undertaken to improve the prognosis of completely resected colon cancer patients. However, several randomized controlled trials adding irinotecan [6], vascular endothelial growth factor (VEGF)-targeting antibodies [7] or epidermal growth factor receptor (EGFR)-targeting antibodies [8] to standard adjuvant chemotherapy failed. Hence, there is a strong need for novel strategies to decrease the high recurrence rate in stage II and III colon cancer patients.
Relevant effects of aspirin on tumor cell lines with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have been demonstrated in vitro for colon [9,10] and breast cancer [11].
Different observational studies have provided evidence for a protective effect of adjuvant aspirin after colorectal cancer resection, particularly in the subset of patients with activating mutations of PIK3CA. A prospective cohort study evaluated the effect of aspirin after the diagnosis of colorectal cancer in relation to PIK3CA-mutational status [12]. Patients with PIK3CA-mutant colorectal cancer taking aspirin had a significant beneficial effect on both cancer-specific and overall survival, with a 82% and 43% relative risk reduction, respectively [12]. Conversely, aspirin had no effect in patients with PIK3CA wild-type colorectal cancer. Although this study provided evidence of a protective effect of aspirin in PIK3CA-mutant colorectal cancer, retrospective analyses are prone to imbalances such as selection bias, and the findings from Liao et al. awaited prospective confirmation since their initial publication The objective of study SAKK 41/13 – the first one in the literature – is to study the benefit of adjuvant aspirin in selected PIK3CA-mutant colon cancer patients in a randomized controlled setting.
Patients and Methods
Patients
SAKK 41/13 (EudraCT No. 2015-001482-57) enrolled patients who were between 18 and 80 years of age, underwent complete (R0) surgical resection of histologically proven stage II (pT3/T4 N0 cM0) or stage III (pTx pN+ cM0) adenocarcinoma of the colon, harboured a centrally confirmed, activating PIK3CA mutation in exons 9 or 20, ECOG performance status 0-2 and with adequate organ function. The timepoint of inclusion was a maximum of 10 weeks from surgical resection. We excluded patients on regular (more than 3 administrations per month) use of aspirin, PTGS2 (aka, cyclooxygenase-2, COX-2) inhibitors or non-steroidal anti-inflammatory drugs (NSAID), patients with relevant upper gastrointestinal bleedings within the past 12 months, multiple concomitant colon malignancies or rectal cancer. Written informed consent was obtained from all patients.
Trial Oversight
The trial was conducted in accordance with the provisions of the Declaration of Helsinki, Good Clinical Practice guidelines (as defined by the International Conference on Harmonisation), applicable regulatory requirements. Each patient (or legally acceptable representative) provided written consent for participation. The study obtained ethics approval from the ethics committee St. Gallen (PB_2016-00550). SAKK 41/13 was designed by the Swiss Group for Clinical Cancer Research who was responsible for data collection, analysis and interpretation, in collaboration with the authors. The manuscript was written by the authors in accordance with Good Publication Practice guidelines. All authors made the decision to publish and vouch for data completeness and accuracy, data analyses and adherence to the study protocol.
Prior to the conduct of the study the trial was listed on clinicaltrials.gov (identifier: NCT02467582).
Trial Design and Treatment
Patients were centrally randomized via the electronic data capture system secuTrial® in a 2:1 ratio to daily aspirin 100 mg versus placebo for a total of 3 years using the minimization methods with 80% allocation probability. Patients, investigators, site staff, monitors, data managers, and designated statisticians were blinded to treatment allocation. A scratch-off card was provided when emergency unblinding was necessary. Randomization was independent of adjuvant chemotherapy which was at the discretion of the investigator. Potential adjuvant chemotherapy regimens included 5-fluorouracil or oral capecitabine either alone or in combination with intravenous oxaliplatin according to standard European guidelines [3].
Diaries were kept by all patients and collected during the study, allowing us to have the full data on how many tablets of aspirin and placebo were taken be each individual patient.
Endpoints
The primary endpoint of this trial is disease-free survival (DFS), defined as the time from surgery until disease recurrence, second cancer or death due to any reason, whatever occurred first. Secondary endpoints include the time to disease recurrence (TTR), overall survival (OS) and adverse events (AE) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCIC CTC) version 5.0. TTR was defined as the time from surgery to disease recurrence or death due to colon cancer. OS is defined as the time from colon cancer surgery to death due to any cause. For all time to event endpoints, patients not experiencing an event were censored at their last assessment.
Trial assessments
Central tumor screening for trial registration was conducted using a validated Sanger sequencing assay for predefined PIK3CA exon 9 or 20 mutations. Central testing was performed at the Institute of Pathology at Cantonal Hospital St.Gallen. Disease assessments using thoraco-abdominal CT scans occurred at baseline and 12-monthly intervals thereafter until disease progression. Clinical examinations including basic laboratory tests including CEA were performed at baseline and 3-monthly intervals thereafter. Electrocardiograms were assessed at baseline. All baseline assessments were performed within 28 days before randomization. Adverse events (AEs), vital signs, and laboratory tests were graded using NCI CTCAE v5.0. Only AEs with grade ≥3 that were possibly, probably or definitely related to treatment were reported.The schedule of evaluations during study treatment and follow-up was done according to the guidelines from the Swiss Association for Gastroenterology (SGG/SSG) [13] and the European Society of Medical Oncology (ESMO) for the follow-up of patients with colon cancer [3]. In addition to these guidelines an imaging using CT scan was performed at 6 and 18 months as well as a colonoscopy at 24 months to early detect recurrences.
Statistical Analysis
According to the intention-to-treat principle, all randomly assigned patients were included in all analyses. For DFS, it was estimated that 185 patients (123 in the aspirin arm, 62 in placebo arm) with 43 events in both study arms would provide a power of 80% to achieve a statistically significant DFS difference for a hazard ratio (HR) of 0.456 and an associated one-sided type I error of 5%. Sample size determination assumed a 3-year DFS of 70% in the placebo arm and 85% in the aspirin arm, assuming constant hazards. With regards to PIK3CA somatic mutations, the number-needed-to-screen was estimated to be 1’088 patients. Two interim analyses were planned after 25% and 50% of the events had been reached. Due to the premature closure of the trial, the final analysis was performed with only 19 events.
For all time-to-event endpoints, the medians as well as rates at 1, 2, 3, 4 and 5 years were estimated using Kaplan-Meier analysis. To detect a potential bias due to imbalances in baseline characteristics, HRs were calculated using both unstratified as well as stratified Cox regression models with the stratification factors as strata, as pre-planned in the protocol. Stratification factors included disease stage (stage II versus stage III colon cancer), tumor sidedness (left versus right hemicolon), type of PIK3CA mutation (exon 9 versus exon 20) and country. Sensitivity analysis was performed to account for non-proportional hazards. For all time-to event endpoints, two-sided 90% confidence intervals (CI) were reported (equivalent to one-sided 95% CIs) to have a lower and upper boundary for the CI as outlined a priori in the study protocol and statistical analysis plan. As this study is comparing aspirin against placebo, one-sided testing was deemed appropriate. All analyses were performed using SAS Version 9.4 (Statistical Analysis System, RRID:SCR_008567; SAS Institute, Cary, NC, USA) and R 4.2.1 (The R Foundation; www.r-project.org).
Results
Overall, 1’040 patients with resected colon cancer stage II and III were screened, of which 180 (17.3%) patients had PIK3CA-mutant colon cancer. Of these 180 patients, 112 patients (62%) were included into the study and randomized to either aspirin (N=74) or placebo (N=38, Figure 1, Supplementary Table S1) between April 2016 and November 2020. The rate of screened and accrued patients is shown in Figure 2. The median time from surgery to treatment start was 9.4 weeks in the aspirin arm and 10.6 weeks in the placebo arm. Due to financial constraints, the trial was prematurely closed. Median treatment duration was 22.1 months (range: 0.4 to 37.5) on aspirin and 21.6 months (range 0.7-37.5) on placebo. Median number of tablets taken was 662 (range 12 to 1,136) on aspirin and 635 (range: 12 to 1,084) on placebo. Compliance with aspirin and placebo intake was high, the median number of pills taken per day and patient was 1 (range 0.7-1) in the aspirin arm und 1 (range 0.6-1) in the placebo arm. Moreover, only 6 patients had a mean number of tablet intake per day of less than 0.9. Median patient age was 66 years (range: 29 to 89), 42.9% of patients were females and 93.8% Caucasians. Of all patients, 46.4% had stage II and 53.6% stage III colon cancer. PIK3CA mutations were found in exon 9 in 57.1% and in exon 20 in 42.9% of patients. 76 (67.9%) received adjuvant chemotherapy. Baseline characteristics were well-balanced between groups (Table 1).
Figure 1. CONSORT diagram.
Enrollment and distribution of patients in the study.
Figure 2. Screened and accrued patients.
Plot representing the number of screened (in red) and accrued (in blue) patients over time (between April 2016 and November 2020). Of 1’040 patients screened, 112 with PIK3CA-mutant colon cancer were included into the study.
Table 1. Patient characteristics.
| Characteristic | Aspirin (n=74) | Placebo (n=38) |
|---|---|---|
| Age (years) | 68 (29 – 79) | 65 (44 – 89) |
| Sex | ||
| Female | 30 (40.5%) | 18 (47.4%) |
| Male | 44 (59.5%) | 20 (52.6%) |
| Ethnicity | ||
| African | 2 (2.7%) | |
| Asian | 3 (4.1%) | |
| Caucasian | 67 (90.5%) | 38 (100%) |
| Hispanic | 1 (1.4%) | |
| Other | 1 (1.4%) | |
| Tumor stage | ||
| Stage II (pT3/T4 N0 cM0) | 34 (45.9%) | 18 (47.4%) |
| Stage III (pTx pN+ cM0) | 40 (54.1%) | 20 (52.6%) |
| Hemicolon | ||
| Left hemicolon | 26 (35.1%) | 16 (42.1%) |
| Right hemicolon | 48 (64.9%) | 22 (57.9%) |
| PIK3CA mutation | ||
| Exon 20 | 32 (43.2%) | 16 (42.1%) |
| Exon 9 | 42 (56.8%) | 22 (57.9%) |
| Position of the mutation | ||
| p.D549 | 1 (1.4%) | 1 (2.6%) |
| p.E542 | 11 (14.9%) | 4 (10.5%) |
| p.E545 | 20 (27.0%) | 9 (23.7%) |
| p.H1047 | 26 (35.1%) | 8 (21.1%) |
| p.Q546 | 8 (10.8%) | 7 (18.4%) |
| other | 8 (10.8%) | 9 (23.7%) |
| ECOG performance status | ||
| 0 | 53 (71.6%) | 29 (76.3%) |
| 1 | 20 (27.0%) | 9 (23.7%) |
| 2 | 1 (1.4%) | |
| Tumor location | ||
| Caecum | 8 (10.8%) | 4 (10.5%) |
| Ascending colon | 30 (40.5%) | 13 (34.2%) |
| Transverse colon | 11 (14.9%) | 5 (13.2%) |
| Splenic flexure | 2 (2.7%) | 1 (2.6%) |
| Descending colon | 11 (14.9%) | 4 (10.5%) |
| Sigmoid colon | 12 (16.2%) | 11 (28.9%) |
| Histopathological grading | ||
| G1 - well differentiated | 4 (5.4%) | 3 (7.9%) |
| G2 - moderately differentiated | 54 (73.0%) | 32 (84.2%) |
| G3 - poorly differentiated | 15 (20.3%) | 3 (7.9%) |
| GX - no tumor identified | 1 (1.4%) | |
| Lymphovascular invasion | ||
| Negative (0) | 40 (54.1%) | 20 (52.6%) |
| Positive (1) | 34 (45.9%) | 18 (47.4%) |
| Perineural invasion | ||
| Negative (0) | 58 (78.4%) | 34 (89.5%) |
| Positive (1) | 16 (21.6%) | 4 (10.5%) |
| Adjuvant chemotherapy | ||
| Yes | 52 (70.3%) | 24 (63.2%) |
| No | 22 (29.7%) | 14 (36.8%) |
Median (range) for continuous variables, frequency (percent) for categorical variables.
At the time of this analysis, nine patients had died, 92 were still alive and 11 were lost to follow-up or withdrew consent. After a median follow-up of 4 years, 19 DFS events occurred. Median DFS was not reached in both arms as less than half of the patients had the event under investigation. The unstratified HR for DFS was 0.57 (90% CI: 0.27 to 1.22) in favor of aspirin (p=0.11), while the stratified HR was 0.57 (90% CI: 0.22 to 1.46) (Figure 3). DFS rates at 3 years were 88.3% (90% CI: 80.1% to 93.3%) in the aspirin arm and 82.4% (90% CI: 68.3% to 90.7%) in the placebo arm. DFS rates at 5 years were 86.5% (90% CI: 77.7% to 92.0%) in the aspirin arm and 72.9% (90% CI: 55.7% to 84.3%) in the placebo arm (Table 2). Sensitivity analyses to account for non-proportional hazards supported the primary analysis results (Supplementary Figure S1). Also, we added the number of pills (aspirin versus placebo) taken per day to a Cox regression model, but this variable had no significant impact on the outcomes (Supplementary Table S2). Overall, the recurrence rates were 9.5% and 18.4% in the aspirin and placebo arm, respectively (Supplementary Table S3). The rates of isolated distant recurrences were 6.8% versus 10.5%, the rates of isolated locoregional recurrences were 1.4% and 2.6%, and the rates of both locoregional and distant recurrences occurred in 1.4% and 5.3%, all in favor of the aspirin group. The unstratified HR for TTR was 0.49 (90% CI: 0.21 to 1.19) in favor of aspirin (p=0.089), the stratified HR for TTR was similar to DFS with 0.56 (90% CI: 0.20 to 1.55) (Figure 4). Median OS was not reached in both arms. The unstratified HR for OS was 0.71 (90% CI: 0.23 to 2.13, p=0.3), the stratified HR 0.60 (90% CI: 0.15 to 2.43) in favor of aspirin (Supplementary Figure S2). CSS could not be calculated as there were only 3 deaths due to colon cancer.
Figure 3. Disease-free survival.
Kaplan-Meier curve of disease-free survival (including unstratified hazard ratio) – comparison between patients randomized to aspirin (in red) versus placebo (in blue).
Abbreviation: HR: hazard ratio
Table 2. Disease-free survival rates including 90% confidence intervals at different time points.
| Years | Aspirin (n=74) | Placebo (n=38) |
|---|---|---|
| 1 | 95.8% [89.5%, 98.4%] | 89.0% [76.7%, 95.0%] |
| 2 | 88.3% [80.1%, 93.3%] | 89.0% [76.7%, 95.0%] |
| 3 | 88.3% [80.1%, 93.3%] | 82.4% [68.3%, 90.7%] |
| 4 | 86.5% [77.7%, 92.0%] | 78.1% [62.5%, 87.8%] |
| 5 | 86.5% [77.7%, 92.0%] | 72.9% [55.7%, 84.3%] |
Figure 4. Time to recurrence.
Kaplan-Meier curve of time to recurrence (including unstratified hazard ratio) – comparison between patients randomized to aspirin (in red) versus placebo (in blue). Abbreviation: HR: hazard ratio
The study treatment was well tolerated, with grade 3 treatment-emergent adverse events occurring in one (1.4%) patient in the aspirin group and 3 (7.9%) patients in the placebo group, respectively. No aspirin-related serious adverse event occurred.
Discussion
The SAKK 41/13 trial provides first prospective-randomized evidence of a protective effect of adjuvant aspirin in patients with resected, PIK3CA-mutant stage II and stage III colon cancer. Indeed, we demonstrated a clinically relevant 43% improvement of the primary endpoint DFS. The absolute difference of DFS at 5 years exceeded 13% in favor of patients randomized to aspirin intake. The relative improvement of TTR was 51%. Hence, the prescription of adjuvant aspirin should be considered in patients with resected, PIK3CA-mutant colon cancer stage II and III.
Many observational and even randomized studies have provided evidence of a protective effect of aspirin in colorectal cancer patients. In a randomized, double-blinded trial 635 patients with previous colorectal cancer were allocated to aspirin 325 mg daily versus placebo. After a median follow-up of 12.8 months one or more adenomas were found in 17% of patients in the aspirin group versus 27% in patients taking placebo (p=0.004) [14]. In the Nurses` Health Study, a prospective cohort study from the United States, 27,077 probands were analyzed. After risk-adjusting in multivariable analyses, probands taking regular aspirin had a significantly lower risk of developing colorectal adenomas. Moreover, there was a clear association between higher daily aspirin doses and lower risk of colorectal adenomas [15]. Interestingly, two prospective cohort studies found a reduction in recurrence of colorectal cancer with regular aspirin intake, however, only in patients with overexpression of PTGS2 [16,17].
In a prospective cohort study [18], 896 patients after resection of colorectal cancer were analyzed for PIK3CA mutations. Patients with PIK3CA mutations taking regular low-dose aspirin were found to have a significantly lower risk of colorectal cancer recurrence with a hazard ratio of 0.11 compared to those not taking aspirin, while no benefit was observed in patients with PIK3CA-unmutated colorectal cancer. Similarly, in the publication by Liao et al., a large benefit of aspirin was found in patients with activating PIK3CA mutations, while no significant differences in cancer-specific and overall survival were observed between patients who did and did not take aspirin with PIK3CA wildtype colorectal cancer [12]. It is hypothesized that the inhibition of PTGS2 by aspirin downregulates PIK3CA activity resulting in an inhibition of tumor cell proliferation. PTGS2 is an important mediator of prostaglandin E2 (PGE2) production, which has been demonstrated to enhance tumor cell survival, angiogenesis and proliferation and reduce apoptosis [19]. Hence, the inhibition of PTGS2 activity has a cytotoxic effect on cancer cells, both in vivo and in vitro [20,21]. In the recently published CALGB/SWOG 80702 (Alliance) study, patients with stage III colon cancer were randomized to celecoxib 400 mg daily for 3 years versus placebo once daily for 3 years in addition to standard adjuvant chemotherapy [22]. Although there was no benefit of celecoxib in the entire patient population [23] statistically significant improvements of DFS and OS were found in the a priori defined subset of patients with predefined activating PIK3CA mutations. Indeed, the benefits for DFS (adjusted HR of 0.56) and OS (adjusted HR of 0.44) were not just statistically significant but also clinically relevant in patients with PIK3CA mutations randomized to celecoxib [22]. Conversely, in the VICTOR study no benefit of rofecoxib versus placebo was found in the subset of patients with a PIK3CA mutation [18]. However, randomization to rofecoxib was after completing chemotherapy in contrast to the CALGB/SWOG and also the present trial. This may explain the difference in efficacy. A study similar to the present prospective, randomized SAKK trial in patients with completely resected colorectal cancer and somatic alterations in the PIK3CA signaling pathway was recently presented as an oral abstract at the 2025 ASCO Gastrointestinal Cancers Symposium [24]. Patients were randomized to 160 mg aspirin or placebo daily for 3 years. After 3 years of follow-up, a statistically significant and clinically relevant decrease in time to recurrence was observed.
The excellent safety profile of aspirin has been extensively demonstrated. A meta-analysis of 24 randomized studies including almost 66`000 patients taking aspirin long-term showed that gastrointestinal hemorrhage occurred in 2.47% of patients taking long-term aspirin compared with 1.42% taking placebo [25]. In the ATT (antithrombotic trialists`) meta-analysis with over 112,000 patients, major gastrointestinal and extracranial bleeds occurred in 0.10% versus 0.07% per year [26]. According to the findings of these large studies, no aspirin-related severe side effect was found in our study. Interestingly, the rate of severe side effects was numerically higher in the placebo group in the present trial. Hence, the use of daily aspirin represents a simple and safe as well as inexpensive intervention.
In the interpretation of the present randomized trial it is of key importance to distinguish statistical significance and clinical relevance [27]. The low event rate is a phenomenon of increasing prognosis over time due to better staging and high surgical quality in comparison to historic data as well as shorter follow-up. Due to the premature study closure, the sample size is small and the trial underpowered.
However, firstly, the absolute differences regarding the primary endpoint DFS and secondary endpoint TTR are of clinical relevance. Secondly, the present SAKK Aspirin Trial must be interpreted in the context of the existing literature: as mentioned above, several prospective cohort studies showed a statistically significant benefit of aspirin in PIK3CA mutant colon cancer patients [12,18]. Furthermore, the newly presented data from the ALASCCA trial, although not yet fully reported, are comparable to the results of our study [24]. More importantly, the Alliance CALGB/SWOG trial demonstrated very similar results to our study with a clinically relevant and – due to a larger sample size – statistically significant DFS and OS benefit, albeit using celecoxib as adjuvant treatment. All these results together with the present trial clearly provide evidence of a protective effect of PTGS2 inhibition, regardless of the chosen drug (aspirin versus PTGS2 inhibitors). Thirdly, the extremely good side-effect profile and very low financial toxicity makes aspirin an attractive adjuvant treatment in resected stage II/III colon cancer patients with an activating PIK3CA mutation.
In conclusion, the SAKK 41/13 study is the first prospective-randomized trial providing suggestive evidence of a protective effect of adjuvant aspirin in patients with resected, PIK3CA-mutant colon cancer. The 43% relative reduction and the absolute DFS reduction of more than 13% at 5 years are clinically relevant. Even though the result is not statistically significant due to the small sample size, adjuvant aspirin warrants individual consideration in patients with resected, PIK3CA-mutant stage II and III colon cancer. The full publication of the ALASCCA trial is eagery awaited [24].
Supplementary Material
Acknowledgments
Not applicable.
Funding/Support
This work was supported by the Swiss National Foundation; Swiss Cancer League; a grant for Oncology Innovation, Merck; Promedica Stiftung; and Fédération Francophone de la Cancérologie Digestive (FFCD). Aspirin and placebo were provided by Bayer. There was a collaboration with the European Organisation for Research and Treatment of Cancer.
Footnotes
Conflict of Interest Statements: Dr Joerger has advisory roles for Novartis, Astra Zeneca, Basilea Pharmaceutica, Bayer, BMS, Debiopharm, MSD, Roche, and Sanofi, received research funding from Swiss Cancer Research and travel grants from Roche, Sanofi, and Takeda. No other disclosures were reported.
Author’s Contributions: Dr Güller had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Concept and design: Güller, Joerger, Hayoz, Horber, Rothgiesser.
Acquisition, analysis, or interpretation of data: Güller, Joerger, Hayoz, Horber, Calmonte, Jochum, Koeberle, De Dosso, Schacher, Inauen, Stahl, Delaunoit, Ettrich, Bodoky, Michel, Koessler.
Drafting of the manuscript: Güller, Joerger, Hayoz.
Critical review of the manuscript for important intellectual content: All authors.
Statistical analysis: Hayoz.
Obtained funding: Güller, Joerger.
Administrative, technical, or material support: Rothgiesser, Hayoz, Calmonte, Jochum.
Supervision: None.
Translational Relevance Statement: The SAKK 41/13 study is the first prospective randomized trial to provide clinical evidence of a protective effect of adjuvant aspirin in patients with resected PIK3CA-mutant colon cancer, with a clinically relevant 43% improvement of DFS and 51% improvement of TTR. No patient experienced aspirin-related serious AEs. Even though the results were not statistically significant due to premature study closure, adjuvant aspirin warrants individual consideration in patients with resected PIK3CA-mutant colon cancer stage II and III.
Data Availability Statement
The data that support the findings of this study as well as the full protocol of the study are available upon reasonable request. Proposals for data access should be submitted to the corresponding author for consideration. Access to deidentified participant data can be granted if the proposal is approved by SAKK; use of the data is intended only for the approved proposal.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data that support the findings of this study as well as the full protocol of the study are available upon reasonable request. Proposals for data access should be submitted to the corresponding author for consideration. Access to deidentified participant data can be granted if the proposal is approved by SAKK; use of the data is intended only for the approved proposal.