(ctDNA) positivity after surgical procedure for stage 3 colon most cancers predicted poorer disease-free survival, however sufferers with ctDNA who acquired Celebrex had higher charges than these on placebo.
Whereas constructive circulating tumor DNA (ctDNA) predicted poorer disease-free survival (DFS) in stage 3 resected colon most cancers, Celebrex (celecoxib) considerably improved DFS outcomes in ctDNA-positive sufferers in comparison with placebo, as demonstrated in outcomes from a subgroup evaluation of the section 3 CALGB (Alliance)/SWOG 80702 trial offered on the 2025 Gastrointestinal Cancers Symposium.
Amongst sufferers with ctDNA-negative colon most cancers following surgical procedure and earlier than therapy with Celebrex or placebo (767 sufferers), the estimated three-year DFS charge was 86.5%. Amongst these with ctDNA-positive illness (173 sufferers), this estimated charge was 33.7%.
“In a subset of sufferers enrolled in CALGB/SWOG 80702, ctDNA standing after surgical procedure and previous to beginning adjuvant remedy was extremely prognostic of DFS and total survival [OS],” Dr. Jonathan Nowak, lead research creator, stated in a press briefing forward of the presentation of the info. “Moreover, ctDNA standing appeared predictive of the good thing about adjuvant [Celebrex].”
Nowak is an investigator on the Hale Household Heart for Pancreatic Most cancers Analysis at Dana-Farber Most cancers Institute and an assistant professor of pathology at Harvard Medical College in Boston.
Glossary:
Circulating tumor DNA: DNA from tumors that’s discovered within the bloodstream.
Illness-free survival: the size of time an individual lives after finishing therapy with none indicators or signs of the illness returning.
Adjuvant remedy: therapy given after the principle therapy to cut back the danger for most cancers recurrence.
General survival: the size of time from prognosis or therapy initiation {that a} affected person with most cancers remains to be alive.
When sufferers have been stratified by therapy with Celebrex versus placebo, investigators confirmed that sufferers with ctDNA-negative illness on the time of research enrollment had comparable outcomes no matter whether or not they acquired Celebrex or placebo, with estimated three-year DFS charges of 87.4% and 85.6%, respectively. Nevertheless, amongst sufferers with ctDNA-positive illness, a major DFS profit was seen within the Celebrex arm versus the placebo arm, with estimated 3-year DFS charges of 41% versus 22.6%, respectively.
Trial Background and Rationale
“Roughly one-third of sufferers identified with colon most cancers have regional lymph node involvement,” Nowak stated. “Regardless of optimum surgical procedure and adjuvant chemotherapy, roughly 20% to 70% of sufferers with stage 3 illness can have a recurrence. Extra methods past customary chemotherapy are wanted to cut back danger of recurrent illness and enhance survival. One promising possibility is to make use of post-resection ctDNA standing, which might inform us if any residual micrometastatic illness is current as a way to assist information adjuvant therapy selections.”
Prior analysis has proven that sufferers with colon most cancers and colon most cancers survivors who obtain aspirin or COX-2 inhibitors expertise favorable DFS and OS outcomes. As an example, a potential, observational research confirmed that amongst 843 evaluable sufferers with stage 3 colon most cancers who have been enrolled in an adjuvant chemotherapy trial, those that used COX-2 inhibitors had improved five-year DFS charge and OS charge in contrast with nonusers.
Trial Design and Beforehand Reported Findings
The CALGB/SWOG 80702 trial formally examined whether or not COX-2 inhibition with Celebrex improved survival in sufferers with colon most cancers. To be eligible for trial enrollment, sufferers wanted to have resected stage 3 colon adenocarcinoma with out metastatic illness, and not less than one pathologically confirmed constructive lymph node. Sufferers weren’t eligible for enrollment in the event that they used nonsteroidal anti-inflammatory medicine at any dose extra typically than two occasions per week or aspirin greater than 325 milligrams thrice per week. Nevertheless, sufferers utilizing low-dose aspirin not exceeding a dose of 100 milligrams per day have been permitted to enroll.
Sufferers have been randomly assigned to obtain each day therapy with both Celebrex or placebo together with both six or 12 therapies of FOLFOX (leucovorin calcium, fluorouracil and oxaliplatin) as follows: placebo plus 12 FOLFOX therapies (arm A), Celebrex plus 12 FOLFOX therapies (arm B), placebo plus six FOLFOX therapies (arm C) or Celebrex plus six FOLFOX therapies (arm D). Celebrex or placebo was continued for 3 years from research drug initiation.
The trial had a goal pattern dimension of two,500 sufferers; 2,526 whole sufferers have been enrolled, and a couple of,524 sufferers have been included.3 DFS served because the trial’s major finish level. Within the major evaluation, investigators noticed no statistically vital DFS distinction with Celebrex versus placebo. Moreover, the consequences of Celebrex therapy weren’t considerably totally different based mostly on assigned adjuvant FOLFOX length.
ctDNA Evaluation Rationale and Extra Findings
Within the Gastrointestinal Cancers Symposium evaluation, Nowak famous that data concerning DFS within the major evaluation indicated {that a} subgroup of sufferers could derive profit from adjuvant Celebrex.
To establish whether or not any affected person subgroup derived better profit from Celebrex therapy in contrast with the general inhabitants, investigators retrospectively carried out a ctDNA evaluation utilizing the Signatera minimal residual illness assay on banked plasma specimens from trial sufferers that have been collected after surgical procedure and earlier than trial enrollment.
Nowak highlighted that findings from this subgroup evaluation “additionally held true in multivariable adjusted fashions for each DFS and OS when the components which can be generally recognized to foretell colon most cancers survival [were] included within the mannequin.”
Within the multivariable evaluation, amongst ctDNA-negative sufferers, Celebrex decreased the danger for most cancers returning by 24% in contrast with placebo, though it was not statistically vital. Concerning OS, Celebrex additionally decreased the danger for loss of life by 16% in contrast with placebo, although these findings have been additionally not statistically vital.
In ctDNA-positive sufferers, findings associated to each DFS and OS have been statistically vital. Particularly, in contrast with placebo, Celebrex decreased the danger for most cancers recurrence and for loss of life every by 37%.
Nowak concluded by explaining that sensitivity and subgroup analyses of this trial are ongoing, in addition to research evaluating the predictive worth of ctDNA for 3 versus six months of adjuvant FOLFOX on this affected person inhabitants.
References:
- Prognostic and predictive position of circulating tumor DNA (ctDNA) in stage III colon most cancers handled with celecoxib: findings from CALGB (Alliance)/SWOG 80702. Nowak JA, et al. J Clin Oncol
- Aspirin and COX-2 inhibitor use in sufferers with stage III colon most cancers. Ng Ok, et al. J Natl Most cancers Inst
- Impact of celecoxib versus placebo added to plain adjuvant remedy on disease-free survival amongst sufferers with stage II colon most cancers: the CALGB/SWOG 80702 (Alliance) randomized medical trial. Meyerhardt JA, et al. JAMA
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