Bridget Hoyt

Stage 3 colon cancer patients who tested MRD+ with Signatera after surgery saw a meaningful survival benefit from Celebrex and chemo: © stock.adobe.com.

Patients with stage 3 colorectal cancer who tested positive for minimal residual disease (MRD) using Signatera after surgery experienced a meaningful survival advantage when Celebrex (celecoxib) was added to standard chemotherapy compared with Signatera-negative patients, who derived no significant benefit, according to findings from the phase 3 CALGB (Alliance)/SWOG 80702 study, which were shared in 

The phase 3 trial is a large, randomized study evaluating the predictive value of circulating tumor DNA (ctDNA) testing in patients who underwent surgery for stage 3 disease. According to the data, which were also shared in a press release from Natera, Inc., patients who were Signatera-positive after surgery saw approximately a 40% reduction in the risk of death when Celebrex was added to FOLFOX chemotherapy compared with chemotherapy plus placebo. Patients who were Signatera-negative, however, did not appear to benefit from adding the drug.

Disease-free survival reached 41.0% at three years in the Celebrex group compared with 22.6% in the placebo group, and overall survival was improved as well. At five years, 61.6% of Signatera-positive patients who received Celebrex remained alive, compared with 39.9% in the placebo group.

“For patients with detectable ctDNA after surgery, adding Celebrex to standard chemotherapy improved both DFS and OS,” Dr. Jonathan Nowak, of Brigham and Women’s Hospital and corresponding author of the research, stated in the news release. “In addition to highlighting Signatera’s predictive abilities in this setting, the publication also underscores its value as a prognostic marker for disease recurrence and survival.”

The publication builds on results initially presented during the 

2025 American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium

The analysis included 940 patients with available plasma samples following surgery. All were randomized to receive standard FOLFOX chemotherapy, with or without Celebrex. Investigators then evaluated whether Signatera MRD status predicted who would benefit from Celebrex treatment, a non-steroidal anti-inflammatory drug.

MRD is a small number of cancer cells left in the body after treatment, according to the University of Texas MD Anderson Cancer Center website. These cells have the potential to come back and cause relapse in patients.

Signatera is designed to detect small amounts of tumor-specific DNA (ctDNA) remaining in the bloodstream after treatment, which can signal residual cancer that is not visible on scans. In this study, the test separated patients into two groups: Signatera-positive patients who still showed detectable ctDNA after surgery, and Signatera-negative patients who did not.

Importantly, investigators found that the benefit of Celebrex in Signatera-positive patients appeared consistent regardless of demographic or clinical factors analyzed. Celebrex improved disease-free survival for Signatera-positive patients with both PIK3CA wild-type tumors and PIK3CA-altered tumors.

Study authors reported no significant risk reduction in recurrence or death for patients who were Signatera-negative after surgery, regardless of PIK3CA status. According to the report, this pattern underscores the importance of identifying MRD, since the presence or absence of detectable ctDNA appeared to guide treatment benefit.

Additional Analysis Strengthened  Treatment Signal

Further analysis evaluated patients whose samples met minimum quality-control criteria for Signatera testing in Natera’s certified laboratory environment.

Approximately 66% of plasma and DNA samples fell into this category for this study. Natera noted that in standard laboratory practice, approximately 99% of samples meet these quality standards, meaning that real-world results may closely reflect this subset analysis.

These findings suggest that MRD testing using Signatera may help identify a population of patients who could benefit from adding Celebrex to conventional chemotherapy, although the benefit is limited to those who remained MRD-positive after surgery.

“This publication marks another important milestone in colorectal cancer research, highlighting Signatera as a critical tool in disease management,” Dr. Adham Jurdi, senior medical director of gastrointestinal oncology at Natera, concluded in the news release. “It further demonstrates Signatera’s predictive utility in identifying, with great precision, patients with MRD who will likely benefit from Celebrex in addition to chemotherapy, regardless of their PIK3CA status.”

Natera Announces Publication of Signatera™ Analysis from Randomized, Phase III CALGB (Alliance)/SWOG 80702 Study in Colorectal Cancer, by Natera, Inc. News release; Dec. 18, 2025.

“What is minimal residual disease (MRD),” by Clayton Boldt. The University of Texas MD Anderson Cancer Center; July 15, 2020.

For more news on cancer updates, research and education, don’t forget to 

Articles

The phase 3 CALGB (Alliance)/SWOG 80702 study demonstrated that stage 3 colorectal cancer patients with minimal residual disease (MRD) who tested positive using Signatera experienced a significant survival advantage when Celebrex was added to standard chemotherapy. This benefit was not observed in Signatera-negative patients. The study highlighted the predictive value of circulating tumor DNA (ctDNA) testing in identifying patients who could benefit from Celebrex, regardless of PIK3CA status. These findings underscore the importance of MRD testing in guiding treatment decisions and improving patient outcomes.

Patients with stage 3 colorectal cancer who tested MRD-positive with Signatera after surgery saw a meaningful survival benefit from Celebrex plus chemotherapy.

This Test Helped Identify Treatment in Colorectal Cancer Surgery 

Most premenopausal women with early breast cancer accepted GnRHa during chemotherapy to preserve ovarian function; cryopreservation uptake was lower: © stock.adobe.com.

Most premenopausal women with early breast cancer accepted gonadotropin-releasing hormone agonist (GnRHa) therapy during chemotherapy to preserve ovarian function, whereas uptake of cryopreservation strategies remained lower, particularly in older premenopausal patients, according to data from the Premenopausal Breast Cancer Patients’ Fertility Preservation (PREFER) study, a large Italian multicenter prospective cohort.

The prospective cohort evaluated fertility preservation strategies in this patient population, and data were shared at the 

. Among patients aged 41 to 45 years, 75% received GnRHa alone, and 25% declined any procedure. Among patients 40 years or younger, 89% received GnRHa, 25% underwent cryopreservation, and 9% underwent no procedure. Acceptance varied according to hormone receptor status, with higher GnRHa uptake in patients with hormone receptor-positive disease. Factors associated with cryopreservation acceptance included younger age, absence of prior children, more recent year of diagnosis, and lower tumor grade.

“Most premenopausal women with early breast cancer accepted the use of a genetic agonist during chemotherapy to preserve ovarian function. Factors associated with acceptance included younger age at diagnosis, no prior children, more recent year of diagnosis, and lower tumor grade,” explained Matteo Lambertini, associate professor and consultant in medical oncology at the University of Genova and IRCCS Policlinico San Martino Hospital in Genova, Italy.

Importantly, controlled ovarian stimulation for oocyte cryopreservation did not negatively impact disease-free survival or overall survival.

PREFER Study: A National Oncofertility Initiative

Oncofertility counseling is recommended for all premenopausal women with newly diagnosed early breast cancer who are candidates for chemotherapy. Standard approaches include cryopreservation of oocytes, embryos, and ovarian tissue, with concurrent GnRHa therapy recommended during chemotherapy to preserve ovarian function. However, data on the uptake of these strategies and reasons for patient refusal have been limited.

The analysis presented at the 2025 symposium represents the first multicenter evaluation of patients enrolled in PREFER between November 2012 and December 2024. PREFER was conducted at 23 Italian centers. Inclusion criteria included stage I to III invasive breast cancer, premenopausal status at diagnosis, age 18 to 45, and candidacy for neoadjuvant or adjuvant chemotherapy. Patients with stage IV disease, prior chemotherapy or radiotherapy, severe psychiatric disorders, or inability to provide consent were excluded.

The primary objective was to evaluate patient needs and choices regarding ovarian function and fertility preservation, including acceptance rates and reasons for refusal. Secondary objectives included safety of controlled ovarian stimulation for oocyte cryopreservation in patients 40 years or younger, with disease-free survival and overall survival as endpoints. Subgroup analyses were performed according to hormone receptor status.

Key Findings: Fertility Preservation by Age and Hormone Receptor Status

In patients aged 41 to 45 years, 78% of those with hormone receptor-positive disease chose GnRHa alone, while 22% had no procedure. Among hormone receptor-negative patients, 69% received GnRHa alone and 31% declined any intervention. The most frequently reported reason for refusal in this age group was completion of family planning (11%).

Among patients 40 years or younger with hormone receptor-positive disease, 90% received GnRHa, 26% underwent cryopreservation, and 8% had no procedure. For hormone receptor-negative patients, 87% received GnRHa, 21% underwent cryopreservation, and 12% had no procedure. Younger age strongly predicted oocyte cryopreservation, as did having no prior children, more recent year of diagnosis, and lower tumor grade. Hormone receptor-negative status was associated with lower uptake relative to hormone receptor-positive disease.

Patients who underwent oocyte cryopreservation (127 patients) were younger, with a median age of 33, compared with 36 among those who did not pursue cryopreservation (406 patients). Parental status strongly influenced decisions: 87% of patients who pursued cryopreservation had no prior children compared with 35% who did not. Tumor grade and type of chemotherapy also differed between groups, with anthracycline- and taxane-based regimens more frequently used in patients not undergoing cryopreservation.

Among patients 40 years or younger, disease-free survival remained high in both groups. Four-year disease-free survival was 95% in patients who underwent oocyte cryopreservation versus 87% among those who did not. Overall survival at four years was 97% in those who had cryopreservation versus 96% in those who did not. These results suggest that undergoing controlled ovarian stimulation does not negatively affect outcomes.

“Results from the PREFER study may provide novel prospective evidence to improve oncofertility counseling for premenopausal women with early breast cancer. From a public health perspective, these findings may help optimize collaboration between oncology and fertility units, including resource allocation,” Lambertini concluded.

“Fertility and ovarian function preservation in premenopausal women with early breast cancer: results from the multicenter prospective PREgnancy and FERtility (PREFER) study,” by Matteo Lambertini. Presented at: San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract GS3-02.

The PREFER study, a large Italian multicenter prospective cohort, evaluated fertility preservation strategies in premenopausal women with early breast cancer. Most patients accepted GnRHa therapy during chemotherapy to preserve ovarian function, while cryopreservation uptake was lower, especially in older patients. Acceptance was influenced by factors such as age, hormone receptor status, and parental status. Controlled ovarian stimulation for oocyte cryopreservation did not negatively impact disease-free or overall survival. These findings may enhance oncofertility counseling and collaboration between oncology and fertility units.

Most premenopausal women with early breast cancer accepted GnRHa during chemotherapy to preserve ovarian function; cryopreservation uptake was lower.

Fertility Decisions Influenced by Age and Parental Status in Premenopausal Breast Cancer 

Dexamethasone before Yescarta reduced the severity of ICANS but did not change how often ICANS or CRS occurred in patients with LBCL.

Using dexamethasone before treatment was associated with less severe immune effector cell-associated neurotoxicity syndrome (ICANS) but did not change how often neurotoxicity or cytokine release syndrome (CRS) occurred in people with relapsed or refractory large B-cell lymphoma (LBCL) treated with Yescarta (axicabtagene ciloleucel; axi-cel), according to data from a single-institution retrospective review presented at the 2025 American Society of Hematology Annual Meeting and Exposition.

Further, peak absolute lymphocyte counts was higher in patients who received dexamethasone prophylaxis, and survival outcomes were comparable between groups.

“Our study shows that, overall, there were no significant differences in rates of CRS and ICANS in general with dexamethasone prophylaxis,” said Dr. Christina Darwish, a second-year fellow at Fox Chase Cancer Center at Temple University Hospital in Philadelphia, Pennsylvania, who presented the data. “However, the rates of grade 3 or 4 ICANS were lower among those who did receive dexamethasone prophylaxis.”

How Dexamethasone Alters the Severity and Pattern of CRS and ICANS

No grade 3 or 4 ICANS events occurred in the dexamethasone group versus 25% in the no-dexamethasone group. The total rate of ICANS events was lower in the group that received dexamethasone versus the group that did not.

No grade 2 ICANS events occurred in either group, and 21% versus 13% in the dexamethasone and no-dexamethasone groups, respectively, had grade 1 immune effector cell-associated neurotoxicity syndrome.

Rates of grade 1, grade 2, and grade 3 CRS were 46%, 25%, and 0% in the dexamethasone group versus 38%, 31%, and 0% in the no-dexamethasone group, respectively. Total CRS rates were 71% and 69% in the groups, respectively.

Impact of Dexamethasone on Treatment Response and Long-Term Outcomes

Prolonged follow-up demonstrated an overall response rate of 89% versus 75% in dexamethasone and no-dexamethasone groups, respectively. Complete response rates were 79% and 69%, respectively. Two-year overall survival was 72.2% versus 67.7%, and progression-free survival was 49.9% versus 60.6%, respectively.

Peak median absolute lymphocyte count was 750 cells per microliter versus 500 cells per microliter in prophylaxis and no-prophylaxis groups, respectively. Median time to peak absolute lymphocyte count was shorter in the dexamethasone group at 9.5 days versus 17 days in the no-dexamethasone group.

Median follow-up for the analysis was 21.4 months in the dexamethasone group and 32.5 months in the no-dexamethasone group.

How the Study Was Structured and Who Was Treated

Forty-four patients were treated with Yescarta, and 28 received dexamethasone prophylaxis, although 16 did not. Those who received dexamethasone prophylaxis received the steroid at 10 mg orally on days 0, 1, and 2 after infusion.

Most patients in the dexamethasone group had diffuse LBCL (68%), followed by follicular lymphoma (29%), and primary mediastinal LBCL (4%). No patients in the dexamethasone group had high-grade B-cell lymphoma or marginal zone lymphoma.

In the no-dexamethasone group, 63% had diffuse large B-cell lymphoma, 19% had follicular lymphoma, 13% had high-grade B-cell lymphoma, and 6% had marginal zone lymphoma. No patients in this group had primary mediastinal large B-cell lymphoma.

Patients in dexamethasone and no-dexamethasone groups had a median age of 63 years and 62 years, respectively; 92% versus 73% had Lugano stage 3 to 4 disease; 71% versus 75% had high-grade lymphoma; 18% versus 13% had bulky disease; and 75% of each group received bridging therapy. With regard to lymphodepleting therapy, most patients in the dexamethasone group received bendamustine and most patients in the no-dexamethasone group received fludarabine and cyclophosphamide.

Most patients in the dexamethasone group and no dexamethasone group had an Eastern Cooperative Oncology Group performance status of 0 to 1; 4% versus 6%, respectively, had a score of 2; and 4% versus 0% had a score of 3. Fifty-seven percent of the dexamethasone group was male versus 31% in the no-dexamethasone group.

Context for Understanding Yescarta and Early Questions About Steroid Use

Yescarta, a cluster of differentiation 19-targeting chimeric antigen receptor T-cell therapy, is approved for the treatment of patients with LBCL relapsed or refractory to chemoimmunotherapy within 12 months of frontline treatment, as well as for the treatment of patients with relapsed or refractory LBCL following 2 or more lines of systemic therapy including diffuse LBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and diffuse LBCL occurring as a result of follicular lymphoma.

The agent also received accelerated approval for the treatment of patients with relapsed or refractory follicular lymphoma following 2 or more lines of prior systemic therapy.

According to Darwish, previous concerns have existed regarding the use of steroids in chimeric antigen receptor T-cell therapies due to worry that steroids may limit chimeric antigen receptor T-cell expansion and efficacy following infusion. However, results from a safety cohort of the ZUMA-1 trial revealed that dexamethasone prophylaxis enhanced safety of Yescarta without compromising efficacy.

“Long-term outcomes of dexamethasone prophylaxis after axicabtagene ciloleucel for non-Hodgkin lymphoma: a single-center retrospective study,” by Dr. Christina Darwish. 

“Yescarta Prescribing information,” by Gilead Sciences. December 9, 2025. https://www.gilead.com/-/media/files/pdfs/medicines/oncology/yescarta/yescarta-pi.pdf

“Prophylactic corticosteroid use with axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory large B-cell lymphoma (R/R LBCL): 2-year follow-up of ZUMA-1 cohort 6,” by Dr. Olalekan Oluwole. 

Dexamethasone prophylaxis in patients with relapsed or refractory large B-cell lymphoma treated with Yescarta was associated with reduced severity of immune effector cell-associated neurotoxicity syndrome (ICANS) but did not affect the incidence of neurotoxicity or cytokine release syndrome (CRS). The study showed no grade 3 or 4 ICANS events in the dexamethasone group, and survival outcomes were similar between groups. Dexamethasone increased peak absolute lymphocyte counts and shortened the time to peak count. Concerns about steroids limiting chimeric antigen receptor T-cell efficacy were not supported by the findings.

Dexamethasone before Yescarta reduced the severity of ICANS but did not change how often ICANS or CRS occurred in patients with LBCL.  

Dexamethasone May Ease Severe Neurotoxicity With Yescarta in LBCL

Race has been identified as an independent prognostic factor in patients with AML receiving intensive chemotherapy.

Among patients with acute myeloid leukemia, Black race has been found to be an independent prognostic factor for lower survival outcomes, regardless of cytogenetics, findings have shown.

Data from a 30-year retrospective analysis of clinical trials were presented at a press briefing at the 67th American Society of Hematology Oncology Annual Meeting and Exposition.

Data collected from 10 ECOG-ACRIN phase 2 and 3 trials between 1984 and 2019 revealed that Black patients experienced 31.3% greater risk of disease recurrence or death and 21.2% greater risk of death than their White counterparts.

Overall Survival (OS): The length of time from diagnosis or the start of treatment that patients are still alive. 

Allogeneic Stem Cell Transplant: A treatment where a patient receives healthy stem cells from a donor (often a sibling or an unrelated volunteer). 

Disease-Free Survival (DFS): The amount of time after treatment during which a patient has no signs of cancer. 

European LeukemiaNet (ELN) Cytogenetic Risk Score: A system used by doctors to group certain types of leukemia — especially acute myeloid leukemia (AML) — into risk categories (favorable, intermediate, or adverse). The score is based on changes in chromosomes or genes found in leukemia cells and helps guide treatment decisions.

“In this large study, we saw that Black race was an independent predictor of inferior survival in patients with AML treated on clinical trials with intensive chemotherapy, and that poorer survival of Black patients was independent of cytogenetics,” said Dr. Shella Saint Fleur-Lominy, a physician at The University of Maryland School of Medicine’s Marlene and Stewart Greenebaum Comprehensive Cancer Center in Baltimore, Maryland, who presented the data.

Further, NPM1 mutations were linked with poorer overall survival (OS) in Black patients versus White patients; Black patients with NPM1-mutated AML had an OS of 19.1 months compared with 8.9 months in White patients harboring NPM1 mutations.

“NPM1 failed to confer favorable outcomes for Black patients, suggesting race can modify the effect of certain somatic mutations,” said Saint Fleur-Lominy.

In general, complete remission rates were similar in Black (58.2%) and White (57.5%) patients, 30-day mortality rates were also similar, at 7.1% and 8.9%, respectively. Notably, a significantly lower portion of Black patients (37.1%) underwent allogeneic stem cell transplant versus White patients (48.5%). Rates of bone marrow transplant were similar in Black patients (19%) and White patients (20.2%).

“Access to allogeneic transplant is a persistent inequity, even in patients with sufficient social support, to be enrolled in clinical trials,” explained Saint Fleur-Lominy.

Patients in other racial groups besides Black and White were 6% higher risk of death and a 14% higher risk of disease recurrence or death compared with White patients.

Cytogenetic Profiles and Risk Prediction in Black and White Patients

While European LeukemiaNet (ELN) cytogenic risk score (RS) predicted OS in Black and White patients, ELN cytogenic RS predicted DFS in White patients but not for Black patients.

OS for Black patients was 57.8 months in those with a favorable ELN cytogenic RS, 14.2 months for those with intermediate RS and 5.8 months for those with an adverse RS. Likewise, OS for White patients with those risk profiles was 60.1 months, 15.2 months and 7.1 months, respectively.

Complete cytogenetic profiles were available for 117 Black patients and 2,162 White patients. Core binding factor AML was observed in a non-significantly higher percentage of Black patients (12.8%) versus White patients (8.3%).

Researchers identified no racial prevalence in FLT3-ITD, CEBPA, TP53 or NPM1 mutations in patients with available data on these mutations.

“There is a need for analysis of large representative AML data set with integration of ancestry, social factors and comprehensive genomic profiling of AML,” said Fleur-Lominy, “in order to elucidate the interaction between race and outcome disparities in AML.”

Patients Characteristics and Statistical Analysis

The study aimed to compare outcomes in Black and White patients, and categorized the patient population as Black, White or other. The study population included 184 Black patients, 3,469 White patients and 156 other patients.

In total, Black patients comprised 1.1% to 11% of respective trial populations. Investigators identified that Black patients were significantly younger at diagnosis, having a median age of 47.9 years versus 53.5 years in White patients. Also of statistical significance, 121 Black patients (65.8%) versus 1,901 White patients (54.8%) were younger than 60.

“Inferior survival in black AML patients treated with intensive chemotherapy in ECOGACRIN clinical trials is independent of cytogenetic profiles” by Dr. Shella Saint Fleur-Lominy et al., 

A 30-year retrospective analysis of clinical trials has identified Black race as an independent prognostic factor for lower survival outcomes in acute myeloid leukemia (AML) patients, irrespective of cytogenetics. Black patients exhibited a higher risk of disease recurrence or death compared to White patients. NPM1 mutations were linked to poorer overall survival in Black patients. Access to allogeneic stem cell transplants was notably lower among Black patients. The study emphasizes the need for comprehensive genomic profiling and consideration of social factors to understand racial disparities in AML outcomes.

Bridget Hoyt

This Test Helped Identify Treatment in Colorectal Cancer Surgery

Fertility Decisions Influenced by Age and Parental Status in Premenopausal Breast Cancer

Dexamethasone May Ease Severe Neurotoxicity With Yescarta in LBCL

Black Patients With AML Face Lower Survival Outcomes

Latest News