Preop chemotherapy confers survival advantage in colorectal cancer with liver metastasis

Giving chemotherapy to patients with synchronous and unresectable liver metastases from colorectal cancer before undergoing primary tumour resection (PTR) helps boost survival outcomes, according to a phase III trial presented at this year’s ASCO Gastrointestinal Cancer Symposium (ASCO GI).

Compared with upfront PTR, preoperative chemotherapy showed superiority in terms of the primary endpoint of progression-free survival (PFS; 10.5 vs 9.1 months), reducing the risk of progression or death by 24 percent (hazard ratio [HR], 0.76, 95 percent confidence interval [CI], 0.60–0.95; p=0.013). [ASCO GI 2023, abstract 132]

In addition, preoperative chemotherapy was associated with significantly better disease control rate (84.4 percent vs 75.0 percent; p=0.037) and a trend toward a more favourable overall survival (OS; 29.4 vs 27.2 months; HR, 0.77, 95 percent CI, 0.58–1.01; p=0.058).

“Most recently, there were three reports of prospective randomized clinical trials comparing the effects of PTR for multiorgan metastatic colorectal cancer followed by chemotherapy [against that of] chemotherapy alone, but the results differed and [were] unconvincing due to the premature study termination and research protocol changes,” said senior study author Dr Jianmin Xu of Zhongshan hospital, Fudan University in Shanghai, China.

“Actually, PTR was preferably performed for patients with asymptomatic synchronous unresectable colorectal liver-limited metastases with conversion therapy purpose [in previous trials],” Xu continued, adding that the findings from the present study provide evidence of the usefulness of adding preoperative chemotherapy. [Lancet Oncol 2010;11:38-47; Ann Oncol 2015;26:702-708; J Clin Oncol 2013;31:1931-1938]

Xu and colleague’s study included 320 adult patients with BRAF wild-type colorectal adenocarcinoma with an asymptomatic resectable primary tumour and synchronous unresectable liver metastases. They were randomly assigned to receive pre-PTR chemotherapy (n=160, median age 57 years, 60.6 percent men) or upfront PTR (n=160, median age 58 years, 63.1 percent men).

All patients had Eastern Cooperative Oncology Group performance status score of 0–1, life expectancy of at least 3 months, and adequate organ function. Baseline characteristics were well balanced in the treatment arms, including the presence of at least three liver metastases (85.0 percent vs 86.2 percent) and RAS genotype (mutated: 41.2 percent vs 38.1 percent), among others.

The chemotherapy regimen used was the modified FOLFOX6 (mFOLFOX6), which included oxaliplatin, leucovorin, and 5-fluorouracil. Based on the patients’ RAS genotype, mFOLFOX6 was given with cetuximab, bevacizumab, or as is. The median follow-up of 36.2 months.

The median PFS rate was 9.9 months, the median OS rate was 28.0 months, and the 3-year OS rate was 37.0 percent in the overall population. The pre-PTR chemotherapy and upfront PTR arms did not differ in terms of the objective response rate (53.1 percent vs 45.0 percent; p=0.146) and the actual resection rate of liver metastases (21.9 percent vs 18.1 percent; p=0.402).

With regard to safety, mild morbidities occurred in both treatment arms, but none of the patients died within 30 days after PTR. The pre-PTR chemotherapy and upfront PTR arms had similar rates of complications (37.7 percent vs 30.8 percent; p=0.201), Clavien–Dindo 3-4 complications (4.5 percent vs 3.8 percent; p=0.759), and predefined grade 3/4 events (42.2 percent vs 40.4 percent; p=0.744).

“The observed toxicity was mostly mild, [and] there were no grade 5 events in either arm,” Xu said.