Phase 3 data indicated that primary tumor resection followed by systemic treatment produced higher 60-day mortality vs systemic treatment alone for patients with metastatic colorectal cancer.
Patients with metastatic colorectal cancer (CRC) who were randomized to receive primary tumor resection followed by systemic treatment had higher 60-day mortality than patients receiving systemic treatment alone, according to results from the phase 3 CAIR04 trial (NCT01606098) published in JAMA Surgery.
Patients in the primary tumor resection arm had a 60-day mortality of 11% (95% CI, 6%-19%) compared with 3% (95% CI, 1%-9%) among patients in the systemic treatment arm (P = .03). Patients with elevated serum levels of lactate dehydrogenase, neutrophils, and aspartate aminotransferase, and/or alanine aminotransferase in the primary tumor resection arm had a significantly higher 60-day postoperative mortality compared those without said characteristics.
“We demonstrated that the 60-day mortality of patients randomized to primary tumor resection followed by systemic therapy was significantly higher than 60-day mortality of patients randomized to systemic treatment only,” the investigators wrote. “Moreover, risk factors for increased postoperative mortality were identified.”
Patient eligibility required individuals be aged 18 years or older with histologically confirmed CRC. Patients also needed to have unresectable metastases, no strong symptoms or signs of primary tumor, resectable tumor based on radiologic imaging, and a WHO performance status between 0 and 2.
The primary aim of the analysis was to evaluate the 60-day mortality between the 2 treatment arms, with a secondary aim focused on the association between patient or biochemical characteristics and 60-day mortality. The primary end point for the CAIR04 trial was overall survival, and secondary end points were progression-free survival and quality of life.
Patients were centrally randomized 1:1 to receive either systemic therapy alone (n = 99) or primary tumor resection followed by systemic therapy (n = 99). Two patients in the primary tumor resection arm were excluded from the final analysis.
The median patient age was 65 years (IQR, 57-70) in the systemic treatment arm and 64 years (IQR, 59-70) in the primary tumor resection arm. Further, 51% and 64% of patients in the systemic treatment and primary tumor resection arms were male, respectively.
Of the deaths that occurred within 60 days among patients in the systemic treatment arm, 1 was the result of disease progression, 1 was due to gastrointestinal toxicity related to treatment, and 1 due to colonic perforation before starting treatment. In the primary tumor resection arm, 2 patients died before resection, 5 died after resection but before systemic treatment, and 4 died after resection and systemic treatment.
Looking at the primary tumor rection arm, 18% (95% CI, 10%-31%) of patients with right-sided colon cancer died within 60 days compared with 4% (95% CI, 1%-14%) of patients with left-sided colon cancer (P = .051).
Grade 3/4 adverse effects (AEs) within 60 days after randomization were seen in 30% (95% CI, 22%-40%) and 23% (95% CI, 15%-32%) of patients in the systemic treatment and primary tumor resection arms, respectively (P = .25). Common AEs in the systemic treatment arm included diarrhea (9%) and pain (8%). In the primary tumor resection arm, common AEs included infections (6%; excluding wound infections), pain (4%), and wound infections (3%).
“In the future, pooling of data of different randomized clinical trials is necessary to confirm these observations and to study whether careful patient selection can potentially identify patients who benefit from primary tumor resection,” the investigators concluded.
van der Kruijssen DEW, Elias SG, Vink GR, et al. Sixty-day mortality of patients with metastatic colorectal cancer randomized to systemic treatment vs primary tumor resection followed by systemic treatment: the CAIRO4 phase 3 randomized clinical trial. JAMA Surg. 2021;156(12):1093-1101. doi:10.1001/jamasurg.2021.4992