For patients diagnosed with resectable colorectal peritoneal metastases (CPM), perioperative systemic therapy was deemed feasible and safe, according to results from a study published in JAMA Surgery.
Participants in this phase 2 randomized superiority trial were patients with pathologically proven, isolated, resectable CPM who had not received treatment 6 months prior to enrollment (ClinicalTrials.gov Identifier: NCT02758951). A total of 79 patients were randomized to the experimental or control groups and included in the analysis.
The experimental group received perioperative systemic therapy consisting of four 3-week neoadjuvant and adjuvant cycles of capecitabine and oxaliplatin, six 2-week neoadjuvant and adjuvant cycles of fluorouracil, leucovorin, and oxaliplatin, or six 2-week neoadjuvant cycles of fluorouracil, leucovorin, and irinotecan along with either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. The control group received cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).
The modified intention-to-treat population included 37 and 42 patients in the experimental and control groups, respectively. In the experimental group, 28 (76%) patients completed all neoadjuvant cycles and all 37 underwent surgery. The number of patients undergoing macroscopic complete CRS-HIPEC in the experimental and control groups were 33 and 36, respectively, which was not significantly different (risk ratio 1.04; 95% CI, 0.88-1.23; P =.74).
The proportion of patients with Clavien-Dindo grade 3 or higher postoperative morbidity was also not significantly different between the experimental and control groups, occurring in 8 of 37 experimental group patients and 14 of 42 patients in the control group (risk ratio, 0.65; 95% CI, 0.31-1.37; P =.25). The objective radiologic response rate of CPM to neoadjuvant treatment was 28%. The percentage of patients with a major pathologic response or a complete pathologic response to neoadjuvant therapy was 38% and 24%, respectively.
There were no surgery-related deaths. The only significant differences between other intraoperative and postoperative outcomes were peritoneal cancer index, ostomy formations, and length of hospital stay, all of which were greater in the control group.
Researchers noted that allowing 3 perioperative systemic regimens was a potential missed opportunity for standardization. Additionally, due to its small sample size, the study was potentially underpowered to detect significant differences in outcomes between groups. Finally, in terms of participant inclusion criteria: 5 patients had unresectable CPM after explorative laparotomy, 35% of eligible patients were not approached for the trial, 2 patients assigned to the experimental group chose upfront surgery, and not all trial treatments were administered within predetermined time frames, with some patients not meeting all eligibility criteria.
Researchers concluded that these results demonstrate the safety and feasibility of perioperative systemic therapy in this patient population and justify conducting a phase 3 trial in the future.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Rovers KP, Bakkers C, Nienhuijs SW, et al. Perioperative systemic therapy vs cytoreductive surgery and hyperthermic intraperitoneal chemotherapy alone for resectable colorectal peritoneal metastases: a phase 2 randomized clinical trial. JAMA Surg. Published online May 19, 2021. doi: 10.1001/jamasurg.2021.1642