LBA-6 Safety, feasibility, tolerability, and preliminary efficacy of perioperative systemic therapy for resectable colorectal peritoneal metastases: Pilot phase of a randomised trial (CAIRO6)

Background:

As CAIRO6 is the first randomized trial investigating perioperative systemic therapy for colorectal peritoneal metastases, this pilot phase was incorporated to assess its feasibility, safety, and tolerability, and response to neoadjuvant treatment.

Methods:

In the pilot phase of this open-label parallel-group trial in nine Dutch tertiary centers, 80 patients with isolated resectable colorectal peritoneal metastases were randomized (1:1) to perioperative systemic therapy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) or CRS-IPEC alone. Perioperative systemic therapy comprised either four three-weekly neoadjuvant and adjuvant cycles of CAPOX (capecitabine, oxaliplatin), six two-weekly neoadjuvant and adjuvant cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin), or six two-weekly neoadjuvant cycles of FOLFIRI (5-luorouracil, leucovorin, irinotecan) and either four three-weekly or six two-weekly adjuvant cycles of capecitabine or 5-fluorouracil/leucovorin, respectively. Bevacizumab was added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. Main outcomes were proportions of complete CRS-HIPEC, major postoperative morbidity, grade ≥3 systemic therapy-related toxicity, and centrally assessed objective radiological and major pathological response to neoadjuvant treatment. Analyses were done modified intention-to-treat in patients starting neoadjuvant treatment (experimental) or undergoing upfront surgery (control).

Results:

In 79 analyzed (of 80 randomized) patients, enrolled between June 2017 and January 2019, experimental (n=37) and control (n=42) arms had comparable proportions of complete CRS-HIPEC (33/37 [89%] versus 36/42 [86%], p=0.74) and major postoperative morbidity (8/37 [22%] versus 14/42 [33%], p=0.25). Grade 3-4 systemic therapy-related toxicity was observed in 13/37 (35%) patients. No treatment-related deaths occurred. Objective radiological and major pathological response rates to neoadjuvant treatment were 28% and 37%, respectively.

Conclusion:

Perioperative systemic therapy is feasible, safe, tolerable, and able to induce tumor response in patients with isolated resectable colorectal peritoneal metastases.