Importance Modulating perioperative inflammation could be associated with fewer postoperative complications and better outcomes in major digestive surgery. The clinical benefit of corticosteroids with this purpose remains controversial. Objective To assess whether preoperative high-dose corticosteroids improve postoperative outcomes after surgery for digestive cancer. Design, Setting, and Participants This double-blind, placebo-controlled, superiority randomized clinical trial included patients undergoing elective surgery with curative intent for digestive cancer. This was a multicenter trial with the participation of 23 French hospitals working as a reference for digestive surgical oncology. Among patients referred for major digestive surgery to the participating centers, those undergoing surgery for digestive cancer with a curative intent between 2019 and 2023 were randomized. Patients undergoing only hepatic surgery without digestive anastomosis were excluded. Interventions Patients included were randomized to receive either 20 mg/kg of intravenous methylprednisolone at the time of anesthesia or a placebo with an identical aspect. Main Outcomes and Measures The primary end point was the onset of major postoperative complications within 30 days after surgery. Secondary end points were postoperative infections, intra-abdominal infections, wound infections, unsatisfactory wound healing within 30 days after surgery, and the length of hospital stay after surgery. Results Among 2461 patients referred for major digestive surgery, 1210 patients (mean [SD] age, 65.9 [11.3] years; 762 male [63%]) undergoing surgery for digestive cancer were randomized. Among the 1188 patients with follow-up at postoperative day 30 (594 per arm), major postoperative complications did not significantly differ between the 2 groups (139 of 594 [23%] receiving methylprednisolone vs 119 of 594 [20%] receiving placebo; P = .16). Secondary outcomes did not differ either between the group receiving methylprednisolone and the group receiving placebo (postoperative infections: 182 of 594 [31%] vs 177 of 594 [30%]; P = .75; intra-abdominal infections: 142 of 594 [24%] vs 126 of 594 [21%]; P = .27; unsatisfactory wound healing: 87 of 594 [15%] vs 69 of 594 [12%]; P = .13; mean [SD] length of hospital stay: 13.21 [8.59] days vs 12.97 [8.1] days; P = .93). Conclusions and Relevance A preoperative pulse dose of corticosteroids had no benefit on postoperative outcomes in elective digestive cancer surgery and should not be recommended in routine practice. Trial Registration ClinicalTrials.gov Identifier: NCT03875690
CDK4/6 inhibitors (CDK4/6i) have markedly changed the treatment landscape for hormone receptors-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC). According to current European guidelines, switching between CDK4/6i is advised when patients experience unacceptable toxicity during therapy. This study aimed to examine patterns of CDK4/6i use and switching strategies due to toxicity in the first line (L1) setting, using data from the ESME cohort, a large real-world database. The ESME MBC cohort is a national cohort collecting individual-level patient data from 18 French Comprehensive Cancer Centers (NCT03275311). For this study, we included all patients aged 18 years or older with newly diagnosed HR+/HER2- MBC who began L1 endocrine treatment (ET) combined with a CDK4/6i. Among these, patients who discontinued CDK4/6i due to toxicity and subsequently reinitiated a different CDK4/6i were selected to evaluate progression-free survival (PFS) following the second CDK4/6i exposure. Between January 1, 2013, and December 31, 2023, 22,965 women treated for HR+/HER2- MBC were enrolled in the ESME database. Among them, 5,553 patients (24%) received L1 ET combined with a CDK4/6i. At the time of analysis, 4,058 patients had discontinued their initial CDK4/6i therapy, 67%, 16% and 17% due to disease progression, toxicity, or other reasons, respectively. Of these, 2,744 (68%), 787 (19%) and 527 (13%) were treated with palbociclib, ribociclib, and abemaciclib, respectively. Aromatase inhibitors were the most commonly used ET partner (78%), followed by fulvestrant (20%). During L1, 231 patients (5.7%) switched CDK4/6i due to toxicity, after a median treatment duration of 2.9 months (range: 0.1-57.6), occurring under palbociclib, ribociclib and abemaciclib in 50 (1.8%), 108 (13.7%), and 73 (13.8%) patients, respectively. The leading causes of discontinuation were gastrointestinal toxicity (28%), hematologic toxicity (26%), and liver toxicity (21%). The median age at the time of CDK4/6i switch was 66 years (range: 32-90), 37% having de novo MBC and 34% presenting with visceral metastases. At the time of analysis, 95 patients were still on treatment while 136 (59%) had discontinued the second CDK4/6i, 40 (29%) due to toxicity after a median rechallenge duration of 3.4 months (range: 0.1-40.0). The toxicity profile was consistent with that observed during L1 therapy, primarily hematologic toxicity (30%), gastrointestinal toxicity (22%), and liver toxicity (10%).With a median follow-up of 28.3 months [95% CI: 23.3-32.9], the median PFS on the second CDK4/6i was 17.9 months [95% CI: 14.7-21.9], and the 3-year overall survival rate was 71.7% [95% CI: 63.1-78.6]. This extensive multicenter retrospective study offers real-world evidence that switching to a second CDK4/6i after toxicity in L1 treatment is feasible. However, one third of this patients’ population discontinued the second CDK4/6i due to toxicity. T. Papazyan, A. Lusque, W. Jacot, T. Grinda, A. Mailliez, E. Brain, T. Bachelot, C. Levy, M. Arnedos, A. Goncalves, V. Massard, M. Mouret-reynier, T. De la Motte Rouge, T. Petit, A. Savoye, I. Desmoulins, M. Leheurteur, L. Bosquet, M. Campone, J. Frenel. Switching CDK4/6 inhibitors due to Toxicity in first-line treatment of HR+/HER2- metastatic breast cancer: Incidence and Outcomes from the ESME Cohort [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-10-21.
Importance:Modulating perioperative inflammation could be associated with fewer postoperative complications and better outcomes in major digestive surgery. The clinical benefit of corticosteroids with this purpose remains controversial. Objective:To assess whether preoperative high-dose corticosteroids improve postoperative outcomes after surgery for digestive cancer. Design, Setting, and Participants:This double-blind, placebo-controlled, superiority randomized clinical trial included patients undergoing elective surgery with curative intent for digestive cancer. This was a multicenter trial with the participation of 23 French hospitals working as a reference for digestive surgical oncology. Among patients referred for major digestive surgery to the participating centers, those undergoing surgery for digestive cancer with a curative intent between 2019 and 2023 were randomized. Patients undergoing only hepatic surgery without digestive anastomosis were excluded. Interventions:Patients included were randomized to receive either 20 mg/kg of intravenous methylprednisolone at the time of anesthesia or a placebo with an identical aspect. Main Outcomes and Measures:The primary end point was the onset of major postoperative complications within 30 days after surgery. Secondary end points were postoperative infections, intra-abdominal infections, wound infections, unsatisfactory wound healing within 30 days after surgery, and the length of hospital stay after surgery. Results:Among 2461 patients referred for major digestive surgery, 1210 patients (mean [SD] age, 65.9 [11.3] years; 762 male [63%]) undergoing surgery for digestive cancer were randomized. Among the 1188 patients with follow-up at postoperative day 30 (594 per arm), major postoperative complications did not significantly differ between the 2 groups (139 of 594 [23%] receiving methylprednisolone vs 119 of 594 [20%] receiving placebo; P = .16). Secondary outcomes did not differ either between the group receiving methylprednisolone and the group receiving placebo (postoperative infections: 182 of 594 [31%] vs 177 of 594 [30%]; P = .75; intra-abdominal infections: 142 of 594 [24%] vs 126 of 594 [21%]; P = .27; unsatisfactory wound healing: 87 of 594 [15%] vs 69 of 594 [12%]; P = .13; mean [SD] length of hospital stay: 13.21 [8.59] days vs 12.97 [8.1] days; P = .93). Conclusions and Relevance:A preoperative pulse dose of corticosteroids had no benefit on postoperative outcomes in elective digestive cancer surgery and should not be recommended in routine practice. Trial Registration:ClinicalTrials.gov Identifier: NCT03875690.
