Primary tumor resection (PTR) followed by chemotherapy did not improve overall survival (OS), compared with chemotherapy alone, in patients with colorectal cancer (CRC) who had asymptomatic primary tumors and synchronous unresectable metastases, according to results published in the Journal of Clinical Oncology.
It’s been unclear whether PTR before chemotherapy improves OS in patients with incurable, advanced CRC, according to the study authors. Although retrospective studies have reported significantly better OS with PTR, there were no prospective trials confirming these results, the authors noted.
The phase 3 iPACS trial was designed to assess the survival benefit of adding upfront PTR to standard chemotherapy in patients with stage IV, asymptomatic CRC who had up to 3 unresectable metastases confined to the liver, lungs, distant lymph nodes, or peritoneum.
The study enrolled 165 patients who were randomly assigned to receive either chemotherapy alone (n=84) or PTR plus chemotherapy (n=81). Chemotherapy consisted of either capecitabine plus oxaliplatin and bevacizumab or oxaliplatin plus leucovorin, 5-fluorouracil, and bevacizumab.
The study’s data and safety monitoring committee recommended early termination of the trial at the first interim analysis based on futility.
At a median follow-up of 22.0 months, the median OS was 25.9 months in the PTR arm and 26.7 months in the chemotherapy-alone arm (hazard ratio [HR], 1.10; 95% CI, 0.76-1.59; one-sided P =.69).
The median progression-free survival was 10.4 months in the PTR arm and 12.1 months in the chemotherapy-alone arm (HR, 1.12; 95% CI, 0.81-1.55; 2-sided P =.48).
The rate of disease progression was 93% in the PTR arm and 87% in the chemotherapy-alone arm.
Grade 2 or higher adverse events (AEs) occurred in 38% of patients in the PTR arm. PTR was associated with a higher frequency and severity of chemotherapy-related non-hematologic AEs.
There were 3 hospital deaths in the PTR arm, 2 of them a result of postoperative complications.
“Given that PTR followed by chemotherapy showed no survival benefit over chemotherapy alone, PTR should no longer be considered a standard of care for patients with CRC with asymptomatic primary tumors and synchronous unresectable metastases,” the authors concluded.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Kanemitsu Y, Shitara K, Mizusawa J, et al. Primary tumor resection plus chemotherapy versus chemotherapy alone for colorectal cancer patients with asymptomatic, synchronous unresectable metastases (JCOG1007; iPACS): A randomized clinical trial. J Clin Oncol. 2021;39(10):1098-1107. doi:10.1200/JCO.20.02447