In a phase III trial (CAIRO6) reported in The Lancet Oncology, Rovers et al found that perioperative systemic therapy was not associated with significant improvement in overall survival vs surgery alone in patients with resectable peritoneal-only metastases of colorectal adenocarcinoma.
Study Details
In the open-label trial, 351 patients (modified intent-to-treat [mITT] population) from all nine Dutch tertiary centers and one Belgian tertiary center were randomly assigned between June 2017 and April 2024 to receive perioperative systemic therapy (n = 173) or surgery alone (n = 178). Treatment consisted of perioperative systemic therapy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC); or upfront CRS-HIPEC alone. At investigator’s choice, perioperative systemic therapy consisted of either four 3-week neoadjuvant and adjuvant cycles of oxaliplatin plus capecitabine (CAPOX), six 2-week neoadjuvant and adjuvant cycles of leucovorin, fluorouracil, and oxaliplatin (FOLFOX), or six 2-week neoadjuvant cycles of leucovorin, fluorouracil, and irinotecan (FOLFIRI), followed by either four 3-week adjuvant cycles of oral capecitabine or six 2-week adjuvant cycles of fluorouracil and leucovorin. Bevacizumab was added to the first three neoadjuvant cycles of CAPOX or the first four neoadjuvant cycles of FOLFOX or FOLFIRI. The primary outcome measure was overall survival assessed in the mITT population.
Key Findings
After a median follow-up of 41 months (interquartile range = 21–62 months), median overall survival was 44 months (95% confidence interval [CI] = 30–54 months) in the perioperative systemic therapy group vs 39 months (95% CI = 31–46 months) in the surgery-alone group (hazard ratio [HR] = 0.85, 95% CI = 0.62–1.15, P = .28).
Among 292 patients who underwent macroscopic complete or near-complete CRS-HIPEC, major 90-day postoperative morbidity occurred in 49 (36%) of 138 patients in the perioperative systemic therapy group and in 40 (26%) of 154 patients in the surgery-alone group. The most common Clavien-Dindo grade 3 to 4 postoperative adverse events were intra-abdominal abscess (12% in 138 patients in the perioperative systemic therapy group vs 10% of 154 patients in the surgery-alone group), anastomotic leakage (9% vs 4%), and fascia dehiscence (9% vs 4%). Ninety-day postoperative mortality occurred in two patients (1%) in the perioperative systemic therapy group (due to anastomotic leakage and cerebrovascular accident) and in one patient (1%) in the surgery-alone group (due to anastomotic leakage).
Among 161 patients in the perioperative systemic therapy group who started systemic therapy, grade 3 or worse systemic therapy–related toxicity occurred in 92 patients (57%); the most common grade 3 to 4 adverse events were hypertension (8%), diarrhea (7%), neutropenia (7%), and thromboembolic events (6%). Systemic therapy–related death occurred in one patient (1%), due to hyperglycemia.
The investigators concluded: “Perioperative systemic therapy cannot be recommended in all patients with resectable colorectal peritoneal-only metastases.”
Koen P. Rovers, PhD, and Ignace H. J. T. de Hingh, PhD, of the Department of Surgery, Catharina Cancer Institute, Eindhoven, Netherlands, are the corresponding authors for The Lancet Oncology article.
DISCLOSURE: The study was funded by the Dutch Cancer Society and F. Hoffman–La Roche. For full disclosures of the study authors, visit thelancet.com.
