Chris Ryan

Maintenance Bavencio with Inlyta treatment interruption is feasible in patients with mRCC: © SciePro - stock.adobe.com.

Among patients with metastatic renal cell carcinoma (mRCC) who responded to frontline Bavencio (avelumab) and Inlyta (axitinib), updated phase 2 TIDE-A study findings presented at the 

 supported the feasibility of maintenance Bavencio with Inlyta treatment interruption.

Progression-free survival (PFS): time a patient lives without disease worsening.

Overall survival (OS): time from diagnosis or treatment start until death.

Objective response rate (ORR): percentage of patients with partial or complete response to treatment.

Partial responses (PR): reduction in tumor size, but not complete remission.

Disease control rate: percentage of patients with stable, partial, or complete response.

Hepatic metastases: cancer spread to the liver.

ECOG performance status of 0 or 1: scale of daily activity ability (0 = fully active, 1 = some limitations).

Bulky or symptomatic disease: large cancer-causing noticeable symptoms.

Findings showed that at a median follow-up of 31.7 months, patients in the overall population (75 patients) achieved a median progression-free survival (PFS) of 27.9 months. The median overall survival (OS) was not reached (NR), and the 24-month OS rate was 85%.

Among the patients who interrupted Inlyta at week 36 (29 patients), the median PFS and OS were both NR; the 24-month PFS and OS rates were 58% and 82%, respectively. The median duration of first Bavencio maintenance was 16 weeks.

“This analysis with a longer follow-up confirmed the feasibility of [Vascular endothelial growth factor, VEGF, tyrosine kinase inhibitors, TKI] interruption and the high response rate after VEGFR TKI reintroduction in patients receiving [Bavencio] maintenance,” lead study author Dr. Daniela Arduini, of Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, and colleagues wrote in a poster presentation of the data.

Following Inlyta interruption, five patients remained on Bavencio monotherapy without disease progression. One patient discontinued Bavencio due to side effects after 35.8 months of maintenance. Two patients continued Bavencio despite evidence of disease progression, and 21 patients restarted Inlyta.

Among patients who restarted Inlyta, the objective response rate (ORR) was 50%, with partial responses (PR) in 10 patients, stable disease in eight patients and progressive disease in two. The median PFS following Inlyta reintroduction was 17.2 months.

“The progression during maintenance with [Bavencio] alone did not affect the response to the subsequent TKI reintroduction. This strategy warrants further investigation in a randomized trial,” study authors added.

TIDE-A enrolled patients with metastatic RCC who had measurable disease, an ECOG performance status of 0 or 1, no bulky or symptomatic disease and no hepatic metastases.

Patients were excluded if they received prior systemic therapy for advanced RCC; received prior adjuvant or neoadjuvant treatment; had an active seizure disorder or evidence of active brain metastases, spinal cord compression, or carcinomatous meningitis; or had a history of another malignancy within two years prior to enrollment, with the exception of adequately treated non-melanoma skin cancer or carcinoma in situ.

All enrolled patients initially received combination therapy with Bavencio at 800 milligrams (mg) once every two weeks plus Inlyta at 5 mg twice per day for 36 weeks. At week 36, patients underwent tumor evaluation, and those who achieved a PR — defined as a tumor volume reduction of at least 30% from baseline — discontinued Inlyta and continued Bavencio monotherapy at 800 mg once every two weeks until disease progression.

If disease progression occurred during Bavencio maintenance — defined as a tumor volume increase of at least 20% from the week 36 assessment — Inlyta was reintroduced at the same dose and discontinued again upon patients achieving a new PR. Patients who had stable disease at week 36 continued combination therapy until disease progression. Those with progressive disease at week 36 stopped all treatment.

The trial’s primary end goal was ORR at eight weeks following Inlyta discontinuation and initiation of Bavencio maintenance after 36 weeks of combination therapy. Secondary end goals included PFS, ORR for the combination period, disease control rate, OS, safety and patient-reported outcomes.

“Updated results of the TIDE-A study evaluating avelumab plus intermittent axitinib in previously untreated patients with metastatic renal cell carcinoma (mRCC),” by Dr. Arduini D, et al., 

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Articles

Updated findings from the TIDE-A study indicate the feasibility of maintenance Bavencio with Inlyta interruption in metastatic renal cell carcinoma (mRCC) patients. At a median follow-up of 31.7 months, the overall population achieved a median progression-free survival (PFS) of 27.9 months, with a 24-month overall survival (OS) rate of 85%. Among patients who interrupted Inlyta, the median PFS and OS were not reached, with 24-month rates of 58% and 82%, respectively. The study supports further investigation of this strategy in a randomized trial.

Updated TIDE-A study findings show that maintenance Bavencio with Inlyta treatment interruption is feasible in patients with metastatic renal cell carcinoma.

Bavencio Maintenance After Inlyta Interruption Shows Feasibility in mRCC

Braftovi plus Erbitux with mFOLFOX6 improved overall response rates in BRAF V600E-mutated metastatic colorectal cancer.

Among patients with metastatic colorectal cancer (mCRC) harboring BRAF V600E mutations, treatment with the combination of Braftovi (encorafenib), Erbitux (cetuximab), and mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) led to a statistically significant and clinically meaningful improvement in overall response rate (ORR) versus mFOLFOX6 alone, according to data from the phase 3 BREAKWATER trial presented at the 2025 Gastrointestinal Cancers Symposium.

Findings demonstrated patients treated with Braftovi plus Erbitux and chemotherapy (110 patients) achieved an ORR of 60.9% compared with 40% for patients treated with chemotherapy alone (110 patients).

In the experimental arm, best responses comprised complete response (CR; 2.7%), partial response (PR; 58.2%), stable disease (SD; 28.2%), progressive disease (PD; 2.7%) non-CR/non-PD (2.7%) and not evaluable (NE; 5.5%). In the control arm, these respective rates were 1.8%, 38.2%, 30.9%, 3.6%, 8.2% and 17.3%.

Overall response rate (ORR): patients who responded partially or completely to treatment.

ECOG performance status: patient's ability to perform daily activities.

Peripheral neuropathy: nerve damage in limbs.

Duration of response (DOR): time cancer responds to treatment.

Overall survival (OS): time from treatment to death.

Complete response (CR): no detectable cancer.

Partial response: significant cancer reduction.

Stable disease: no significant cancer change.

Progressive disease (PD): cancer growth or spread.

Progression-free survival: the time a patient lives without their disease spreading or worsening.

“[Data from the BREAKWATER] study support [Braftovi] plus [Erbitux] and mFOLFOX6 as a new standard of care in the first line for patients with BRAF V600E–mutated mCRC and formed the basis of the accelerated approval by the FDA,” lead study author Dr. Scott Kopetz said in a presentation of the data.

Kopetz is deputy chair for Translational Research and a professor in the Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine; leader of the Department of Cancer Center Support Grant, GI Program; TRACTION medical director in the Division of Therapeutics Discovery Division; and associate vice president for Translational Integration at The University of Texas MD Anderson Cancer Center in Houston.

In December 2024, the FDA granted accelerated approval to Braftovi in combination with Erbitux and mFOLFOX6 for the treatment of patients with mCRC harboring a BRAF V600E mutation, as detected by an FDA-approved test.

Investigators for the open-label, multicenter study enrolled patients at least 16 years of age (or at least 18 years of age based on the country) with BRAF V600E–mutated mCRC per local or central laboratory testing. Prior systemic therapy in the metastatic setting was not allowed.

Patients were excluded if they received prior treatment with a BRAF or EGFR inhibitor; had symptomatic brain metastases; or harbored a RAS mutation. Patients with mismatch repair–deficient/microsatellite instability–high disease were excluded; however, these patients were allowed to enroll if they were ineligible to receive immune checkpoint inhibitors due to a pre-existing medical condition.

The study enrolled 637 patients who were randomly assigned to receive Braftovi plus Erbitux alone (158 patients); Braftovi plus Erbitux and mFOLFOX6 (236 patients); or standard-of-care mFOLFOX6 alone (243 patients). Data for the Braftovi/Erbitux arm will be reported at a later date.

Patients were stratified by region (United States/Canada versus Europe versus rest of world) and ECOG performance status (0 versus 1).

Progression-free survival and ORR for Braftovi plus Erbitux and mFOLFOX6 versus mFOLFOX6 alone served as the trial’s dual primary end points. Notably, for this analysis, ORR was assessed in the first 110 patients enrolled in the respective arms. Overall survival (OS) was a key secondary end point. OS was only tested if the ORR difference was statistically significant.

Among all enrolled patients between the Braftovi plus Erbitux and mFOLFOX6 arm and the mFOLFOX6 arm (479 patients), the median age was 61 years. Most patients were male (50.5%), had an ECOG performance status of 0 (54.3%), right-sided tumors (61%), two or fewer organs involved (52.4%), liver metastases (62.6%), a carcinoembryonic antigen level of more than 5 µg/L (68.7%) and a C-reactive protein level of no more than 10 milligrams/L (50.9%).

The median treatment duration was 28.1 weeks in the Braftovi plus Erbitux and mFOLFOX6 arm versus 20.4 weeks in the mFOLFOX6 arm. All patients in both arms were randomly assigned; however, 2.1% and 5.8% of patients were not treated, respectively.

As of the data cutoff date of Dec. 22, 2023, 58.1% of patients in the Braftovi plus Erbitux and mFOLFOX6 arm were still receiving treatment. Reasons for discontinuation included side effects (AEs; 4.7%), death (3.4%), PD (20.8%), patient withdrawal (5.5%), global deterioration of health status (3.4%) and other (4.2%). In the mFOLFOX6 arm, 33.7% of patients were still receiving treatment at data cutoff; reasons for discontinuation comprised AEs (9.1%), death (4.1%), PD (31.7%), patient withdrawal (11.5%), deterioration of global health status (1.6%) and other (8.2%).

The median time to response was 7.1 weeks (range, 5.7-53.7) in the Braftovi plus Erbitux and mFOLFOX6 arm versus 7.3 weeks (range, 5.4-48.0) in the chemotherapy arm. The estimated duration of response (DOR) was 13.9 months and 11.1 months, respectively. In the experimental arm, the six- and 12-month DOR rates were 68.7% and 22.4%, respectively. In the control arm, these respective rates were 34.1% and 11.4%.

Kopetz noted that the ORR benefit was consistent across subgroups with the experimental regimen.

Regarding safety, any-grade treatment-emergent AEs (TEAEs) occurred in 99.6% of patients in the experimental arm (231 patients) versus 97.8% of patients in the control arm (228 patients). The rates of grade 3 (severe) or 4 (life-threatening) TEAEs were 74% and 61%, respectively. The respective rates of grade 5 (death) TEAEs were 4.3% and 4.4%. Serious TEAEs were reported in 37.7% of patients in the Braftovi plus Erbitux and mFOLFOX6 arm versus 34.6% of patients in the mFOLFOX6 arm.

In the Braftovi plus Erbitux and mFOLFOX6 group, TEAEs led to permanent discontinuation of any treatment, dose reduction of any treatment and dose interruption of any treatment in 20.8%, 61% and 84.8% of patients, respectively. These respective rates were 14.9%, 47.8% and 64% in the control arm.

Specifically in the experimental arm, TEAEs led to the discontinuation of Braftovi, Erbitux and mFOLFOX6 in 11.7%, 13% and 15.6% of patients, respectively. The respective rates of dose reduction for each treatment due to TEAEs were 22.1%, 6.1% and 55.8%. The rates of dose interruptions due to TEAEs were 56.7% for Braftovi, 58.4% for Erbitux and 75.8% for mFOLFOX6.

Treatment-related AEs (TRAEs) of any grade were observed in 98.7% of patients in the experimental arm and 93% of patients in the mFOLFOX6 arm. The rates of grade 3 or 4 TRAEs were 69.7% and 53.9%, respectively. No grade 5 TRAEs occurred in the Braftovi plus Erbitux and mFOLFOX6 group; one patient (0.4%) experienced a grade 5 TRAE in the control arm. The rates of serious TRAEs were 18.2% and 19.3%, respectively.

The most common TEAEs reported in the experimental arm included nausea (grade 1/2, 48.5%; grade 3 or worse, 2.6%), anemia (25.5%; 10.8%), diarrhea (32.9%; 1.3%), decreased appetite (31.2%; 2.2%), vomiting (29.9%; 3.5%), decreased neutrophil count (13.9%; 18.2%), asthenia (22.5; 4.3%), pyrexia (24.2%; 1.7%), peripheral sensory neuropathy (19%; 5.6%), rash (23.8%, 0.9%), fatigue (21.6%; 2.6%), peripheral neuropathy (16.5%; 6.9%), arthralgia (21.2%; 0.9%), neutropenia (7.4%; 14.7%), alopecia (21.2%; 0%) and constipation (19.9%; 0.4%).

In the control arm, the most frequently reported TEAEs were nausea (grade 1/2, 45.2%; grade 3 or worse, 3.1%), anemia (19.3%; 3.5%), diarrhea (43.4%; 3.5%), decreased appetite (23.7%; 1.3%), vomiting (18.9%; 2.2%), decreased neutrophil count (11.4%; 16.7%), asthenia (13.2%; 1.3%), pyrexia (12.7%; 0.4%), peripheral sensory neuropathy (19.3%; 2.2%), rash (2.6%, 0%), fatigue (22.4%; 2.6%), peripheral neuropathy (18.4%; 2.6%), arthralgia (3.5%; 0%), neutropenia (13.2%; 9.2%), alopecia (9.6%; 0%) and constipation (18.9%; 0.4%).

“BREAKWATER: Analysis of first-line encorafenib + cetuximab + chemotherapy in BRAF V600E-mutant metastatic colorectal cancer,” By Dr. Scott Kopetz, et al. 

The combination of Braftovi (encorafenib), Erbitux (cetuximab), and mFOLFOX6 significantly improved the overall response rate (ORR) in patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC) compared to mFOLFOX6 alone, as demonstrated in the phase 3 BREAKWATER trial. The experimental regimen achieved a 60.9% ORR versus 40% with chemotherapy alone. The FDA granted accelerated approval for this combination in December 2024. Safety profiles showed high rates of treatment-emergent adverse events (TEAEs), with notable differences in discontinuation and dose modification rates between the treatment arms.

Patients with BRAF V600E-mutated metastatic colorectal cancer experienced improved responses when treated with Braftovi plus Erbitux and mFOLFOX6.

Braftovi Plus Erbitux With mFOLFOX6 May Improve Responses in BRAF V600E+ mCRC

In resectable, locally advanced esophageal squamous cell carcinoma, neoadjuvant Tyvyt plus chemoradiotherapy led to an improvement in response rates.

Among patients with resectable, locally advanced esophageal squamous cell carcinoma (ESCC), treatment with Tyvyt (sintilimab) plus neoadjuvant chemoradiotherapy (CRT) generated an improvement in pathological complete response (pCR) rate compared with CRT alone, according to data from the phase 3 SCIENCE trial which were shared at the 2025 ASCO Gastrointestinal Cancers Symposium.

However, an improvement in pCR rate was not observed for the experimental regimen of neoadjuvant Tyvyt plus chemotherapy versus Tyvyt plus CRT or CRT alone.

Findings from the study conducted at more than 14 centers in China showed that patients treated with Tyvyt plus CRT (45 patients) achieved a pCR rate of 60% compared with 13% for those given Tyvyt plus chemotherapy (46 patients). The pCR rate was 47.3% in patients given CRT alone.

“Adding [Tyvyt] … to neoadjuvant CRT may improve the pathological outcomes without increasing surgical risks,” lead study author Dr. Xuefeng Leng, of the Department of Thoracic Surgery at Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, said in a presentation of the data. “Neoadjuvant CRT combined with [immunotherapy] has the potential to become the new standard of care [SOC] in the near future.”

Adjuvant: cancer treatment given after the initial treatment to reduce the risk of the cancer returning.

Chemoradiotherapy (CRT): a cancer treatment that combines chemotherapy and radiation therapy.

Disease control rate: a percentage of patients who have a complete response, partial response or stable disease after treatment

Intensity modulated radiation therapy (IMRT): a type of radiation therapy that uses computer-controlled beams of varying intensity to precisely target a tumor.

Major pathological response rate: the percentage of patients in a study who exhibit a major pathological response after receiving neoadjuvant therapy.

Overall response rate: percentage of patients who have a complete or partial response to a treatment.

Pathological complete response (pCR): the absence of cancer cells in tissue samples after treatment.

R0 resection rate: percentage of patients who have a complete resection of a tumor with a negative resection margin.

During the presentation, Leng noted that neoadjuvant chemotherapy or CRT is the current SOC in East Asia for patients with resectable, locally advanced ESCC. “However, the optimal neoadjuvant treatment strategy [for this patient population] remains uncertain,” he explained. “This is why we focused on this question and started this study.”

In the randomized, multicenter SCIENCE trial, investigators enrolled patients 18 to 75 years of age with histologically diagnosed thoracic ESCC that was locally and previously untreated.

Patients were randomly assigned to receive neoadjuvant treatment with 200 milligrams (mg) of Tyvyt plus 220 milligrams per square meter (mg/m

) of Abraxane(nab-paclitaxel) and area under the curve 3 to 5 of carboplatin on day 1 of each three-week cycle for two cycles; the combination of Tyvyt, nab-paclitaxel and carboplatin once every three weeks for two cycles with concurrent intensity modulated radiation therapy (IMRT) or image-guided radiation therapy (IGRT) totaling 41.4 gray (Gy); or nab-paclitaxel plus carboplatin once every three weeks for two cycles with concurrent IMRT/IGRT.

Following neoadjuvant therapy, patients proceeded to surgery. For patients who achieved a R0 resection, those with a pCR underwent surveillance, and those without a pCR received adjuvant Tyvyt. Adjuvant treatment for patients without a R0 resection was determined by a multidisciplinary team.

The study’s coprimary end points were pCR rate and event-free survival. Secondary end points included overall response rate, disease control rate, R0 resection rate, major pathological response rate and safety. Biomarkers were an exploratory end point.

As of the September 2024 data cutoff, all enrolled patients in each arm received and completed two cycles of neoadjuvant therapy before undergoing definitive surgery.

All patients in the Tyvyt plus CRT arm experienced a response. The tumor regression grades in this arm were 0 (60%), 1 (24.4%) and 2 (15.6%); no patients had a tumor regression grade of 3. In the Tyvyt plus chemotherapy arm, tumor regression grades were 0 (13%), 1 (13%), 2 (52.2%) and 3 (21.7%). In the CRT arm, these grades were 0 (47.3%), 1 (25.5%), 2 (21.8%) and 3 (5.5%).

R0 resection was achieved by all patients in all three arms. The median duration of surgery was 4.2 hours in the Tyvyt plus chemotherapy arm, four hours in the CRT arm and 4.4 hours in the Tyvyt plus CRT arm. A thoracoscopic McKeown procedure was used for 50%, 63.6% and 71.1% of patients, respectively. The respective rates of robotic-assisted McKeown procedures were 47.8%, 34.5% and 28.9%. An Ivor-Lewis procedure was used for 2.2%, 1.8% and 0% of patients, respectively.

Surgical complications were reported in 71.7% of patients in the Tyvyt plus chemotherapy arm, 49.1% of patients in the CRT arm and 46.7% of patients in the Tyvyt plus CRT arm. Anastomotic leak did not occur in any patients in the Tyvyt plus chemotherapy arm compared with 5.5% of patients in the CRT group and 2.2% of patients in the Tyvyt plus CRT group. The rates of postoperative hemorrhage were 10.9%, 1.8% and 0% for the Tyvyt plus chemotherapy, CRT, and Tyvyt plus CRT groups, respectively. The respective rates of pulmonary infection were 67.4%, 47.3% and 44.4%.

Safety data showed that the most common any-grade treatment-emergent side effects reported in at least 5% of patients in any arm included decreased white blood cell count (Tyvyt plus chemotherapy, 8.7%; CRT, 56.4%; Tyvyt plus CRT, 75.6%), decreased neutrophil count (4.3%; 27.3%; 55.6%), hypoalbuminemia (19.6%; 50.9%; 13.3%), decreased lymphocyte count (2.2%; 41.8%; 24.4%), decreased platelet count (4.3%; 34.5%; 35.6%), anemia (2.2%; 30.9%; 22.2%), increased alanine aminotransferase (0%; 0%; 8.9%), increased aspartate aminotransferase (0%; 0%; 6.7%) and esophageal anastomotic leak (0%; 5.5%; 0%).

Grade 3 or higher side effects included lymphopenia (Tyvyt plus chemotherapy, 0%; CRT, 30.9%; Tyvyt plus CRT, 11.1%), leukopenia (4.3%; 29.1%; 24.4%), neutropenia (2.2%; 16.4%; 8.9%), thrombocytopenia (2.2%; 1.8%; 4.4%), anemia (0%; 1.8%; 0%), hyperglycemia (0%; 1.8%; 0%) and hypernatremia (0%; 1.8%; 0%).

“Preliminary results from the multicenter, randomized phase III trial (SCIENCE): Comparing chemotherapy plus sintilimab and chemoradiotherapy plus sintilimab versus chemoradiotherapy for neoadjuvant treatment in resectable locally advanced esophageal squamous cell carcinoma” by Dr. Xuefeng Leng, et al. 

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In patients with resectable, locally advanced esophageal squamous cell carcinoma, the combination of Tyvyt (sintilimab) and neoadjuvant chemoradiotherapy (CRT) significantly improved the pathological complete response (pCR) rate compared to CRT alone, as demonstrated in the phase 3 SCIENCE trial. However, Tyvyt plus chemotherapy did not show similar improvements. The study, conducted across multiple centers in China, highlighted the potential of Tyvyt plus CRT to become a new standard of care, with favorable surgical outcomes and manageable safety profiles compared to other treatment regimens.

Neoadjuvant Tyvyt With Chemo Improve Responses in Resectable, Locally Advanced ESCC

(ctDNA) positivity after surgery for stage 3 colon cancer predicted poorer disease-free survival, but patients with ctDNA who received Celebrex had better rates than those on placebo.

While positive circulating tumor DNA (ctDNA) predicted poorer disease-free survival (DFS) in stage 3 resected colon cancer, Celebrex (celecoxib) significantly improved DFS outcomes in ctDNA-positive patients compared to placebo, as demonstrated in results from a subgroup analysis of the phase 3 CALGB (Alliance)/SWOG 80702 trial presented at the 2025 Gastrointestinal Cancers Symposium.

Among patients with ctDNA-negative colon cancer following surgery and before treatment with Celebrex or placebo (767 patients), the estimated three-year DFS rate was 86.5%. Among those with ctDNA-positive disease (173 patients), this estimated rate was 33.7%.

“In a subset of patients enrolled in CALGB/SWOG 80702, 

 after surgery and prior to starting adjuvant therapy was highly prognostic of DFS and overall survival [OS],” Dr. Jonathan Nowak, lead study author, said in a press briefing ahead of the presentation of the data. “Additionally, ctDNA status appeared predictive of the benefit of adjuvant [Celebrex].”

Nowak is an investigator at the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute and an assistant professor of pathology at Harvard Medical School in Boston.

Circulating tumor DNA: DNA from tumors that is found in the bloodstream.

Disease-free survival: the length of time a person lives after completing treatment without any signs or symptoms of the disease returning.

Adjuvant therapy: treatment given after the main treatment to reduce the risk for cancer recurrence.

Overall survival: the length of time from diagnosis or treatment initiation that a patient with cancer is still alive.

When patients were stratified by treatment with Celebrex versus placebo, investigators showed that patients with ctDNA-negative disease at the time of study enrollment had similar outcomes regardless of whether they received Celebrex or placebo, with estimated three-year DFS rates of 87.4% and 85.6%, respectively. However, among patients with ctDNA-positive disease, a significant DFS benefit was seen in the Celebrex arm versus the placebo arm, with estimated 3-year DFS rates of 41% versus 22.6%, respectively.

“Approximately one-third of patients diagnosed with colon cancer have regional lymph node involvement,” Nowak said. “Despite optimal surgery and adjuvant chemotherapy, approximately 20% to 70% of patients with stage 3 disease will have a recurrence. Additional strategies beyond standard chemotherapy are needed to reduce risk of recurrent disease and improve survival. One promising option is to use post-resection ctDNA status, which can tell us if any residual micrometastatic disease is present in order to help guide adjuvant treatment decisions.”

Prior research has shown that patients with colon cancer and colon cancer survivors who 

 or COX-2 inhibitors experience favorable DFS and OS outcomes. For instance, a prospective, observational study showed that among 843 evaluable patients with stage 3 colon cancer who were enrolled in an adjuvant chemotherapy trial, those who used COX-2 inhibitors had improved five-year DFS rate and OS rate compared with nonusers.

Trial Design and Previously Reported Findings

The CALGB/SWOG 80702 trial formally tested whether COX-2 inhibition with Celebrex improved survival in patients with colon cancer. To be eligible for trial enrollment, patients needed to have resected stage 3 colon adenocarcinoma without metastatic disease, and at least one pathologically confirmed positive lymph node. Patients were not eligible for enrollment if they used nonsteroidal anti-inflammatory drugs at any dose more often than two times per week or aspirin more than 325 milligrams three times per week. However, patients using low-dose aspirin not exceeding a dose of 100 milligrams per day were permitted to enroll.

Patients were randomly assigned to receive daily treatment with either Celebrex or placebo in combination with either six or 12 treatments of FOLFOX (leucovorin calcium, fluorouracil and oxaliplatin) as follows: placebo plus 12 FOLFOX treatments (arm A), Celebrex plus 12 FOLFOX treatments (arm B), placebo plus six FOLFOX treatments (arm C) or Celebrex plus six FOLFOX treatments (arm D). Celebrex or placebo was continued for three years from study drug initiation.

The trial had a target sample size of 2,500 patients; 2,526 total patients were enrolled, and 2,524 patients were included.

 DFS served as the trial’s primary end point. In the primary analysis, investigators observed no statistically significant DFS difference with Celebrex versus placebo. Furthermore, the effects of Celebrex treatment were not significantly different based on assigned adjuvant FOLFOX duration.

ctDNA Analysis Rationale and Additional Findings

In the Gastrointestinal Cancers Symposium analysis, Nowak noted that information regarding DFS in the primary analysis indicated that a subgroup of patients may derive benefit from adjuvant Celebrex.

To identify whether any patient subgroup derived greater benefit from Celebrex treatment compared with the overall population, investigators retrospectively performed a ctDNA analysis using the Signatera minimal residual disease assay on banked plasma specimens from trial patients that were collected after surgery and before trial enrollment.

Nowak highlighted that findings from this subgroup analysis “also held true in multivariable adjusted models for both DFS and OS when the factors that are commonly known to predict colon cancer survival [were] included in the model.”

In the multivariable analysis, among ctDNA-negative patients, Celebrex reduced the risk for cancer returning by 24% compared with placebo, although it was not statistically significant. Regarding OS, Celebrex also reduced the risk for death by 16% compared with placebo, though these findings were also not statistically significant.

In ctDNA-positive patients, findings related to both DFS and OS were statistically significant. In particular, compared with placebo, Celebrex reduced the risk for cancer recurrence and for death each by 37%.

Nowak concluded by explaining that sensitivity and subgroup analyses of this trial are ongoing, as well as studies evaluating the predictive value of ctDNA for three versus six months of adjuvant FOLFOX in this patient population.

Prognostic and predictive role of circulating tumor DNA (ctDNA) in stage III colon cancer treated with celecoxib: findings from CALGB (Alliance)/SWOG 80702. Nowak JA, et al. 

Aspirin and COX-2 inhibitor use in patients with stage III colon cancer. Ng K, et al. 

Effect of celecoxib versus placebo added to standard adjuvant therapy on disease-free survival among patients with stage II colon cancer: the CALGB/SWOG 80702 (Alliance) randomized clinical trial. Meyerhardt JA, et al. 

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Celebrex (celecoxib) significantly improved disease-free survival (DFS) in ctDNA-positive stage 3 resected colon cancer patients compared to placebo, as shown in a subgroup analysis of the CALGB/SWOG 80702 trial. ctDNA status post-surgery was highly prognostic of DFS and overall survival (OS). While Celebrex did not show a significant DFS benefit in the overall trial population, it reduced cancer recurrence and death risk by 37% in ctDNA-positive patients. Ongoing analyses aim to further evaluate ctDNA's predictive value for adjuvant therapy duration.

Although ctDNA positivity generally meant worse disease-free survival in stage 3 resected colon cancer, patients with ctDNA who received Celebrex had significantly better rates versus placebo.

Chris Ryan

Bavencio Maintenance After Inlyta Interruption Shows Feasibility in mRCC

Braftovi Plus Erbitux With mFOLFOX6 May Improve Responses in BRAF V600E+ mCRC

Neoadjuvant Tyvyt With Chemo Improve Responses in Resectable, Locally Advanced ESCC

ctDNA Status May Predict Disease-Free Survival With Celebrex in Colon Cancer

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