Study suggests optimal approach for unresectable colorectal liver disease

For patients with early unresectable liver metastases from colorectal cancer, FOLFOXIRI and bevacizumab (Avastin) were the ‘preferred’ systemic induction regimens for right-sided or right-sided patients. RAS- again BRAF V600E mutated primary tumor according to a phase III randomized trial.

Among these patients, median progression-free survival (PFS) was 9.0 months in the FOLFOX or FOLFIRI plus bevacizumab arm compared to 10.6 months in the FOLFOXIRI plus bevacizumab arm (stratified HR 0.76, 95%CI 0.60-0.98, P.= 0.032), reported Cornelis Punt, M.D., Ph.D., Utrecht University Medical Center, Utrecht University, The Netherlands, and colleagues from the Dutch Colorectal Cancer Study Group.

The combination of FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, irinotecan) and bevacizumab also significantly increased the objective response rate (54% vs 33%, P.=0.0004) and disease control rate (93% vs 81%, P.=0.0028) comparing FOLFOX or FOLFIRI with bevacizumab, they stated: Lancet Oncology.

Complete local treatment was given in 51% and 37% of patients, respectively (P.=0.013).

“Although the benefit in median progression-free survival was small, an increase in the proportion of patients receiving complete local therapy may be considered of greater clinical significance,” Panto et al. there is

Pant et al. also evaluated patients with different left and right halves. RAS again BRAF V600E wild-type tumors treated with FOLFOX or FOLFIRI in combination with either bevacizumab or the anti-EGFR antibody panitumumab (Vectibix).

Median PFS was similar in bevacizumab-treated and panitumumab-treated patients (10.8 and 10.4 months, respectively; stratified HR 1.11, 95% CI 0.84 to 1.48; P.=0.46).

The addition of panitumumab significantly increased the objective response rate (80% vs. 53%, P.<0.0001), and the complete local treatment rate was 58% in both groups.

“Considering that topical treatment remains the only treatment that offers a chance of prolonging life, we must keep in mind the fact that better objective responses did not translate into better conversion rates,” said Katsunori Imai, M.D., Ph.D. writes Hideo Baba. , M.D., Ph.D., both at Kumamoto University in Japan, Commentary accompanying the study. “In general, objective response rates are substantially related to resection rates.”

Punt et al. said that this association between objective response rate and resection rate will be analyzed in the future, and that overall survival data “should be awaited before drawing any definitive conclusions.”

Regarding safety, serious adverse events occurred in 31% of patients receiving FOLFOX or FOLFIRI plus bevacizumab and 52% of patients receiving FOLFOXIRI plus bevacizumab.

“The significantly higher incidence of grade 3 or higher adverse events with FOLFOXIRI plus FOLFOX or FOLFIRI plus bevacizumab is consistent with previous studies, primarily diarrhea and non-febrile neutropenia. This was due to the high incidence,” the authors noted.

Panitumumab was also associated with increased toxicity, which is consistent with previous studies, Pant and colleagues said. Serious adverse events occurred in 36% of patients in the bevacizumab group and 42% in the panitumumab group, the difference being primarily due to a higher incidence of skin toxicity and diarrhea with panitumumab; There was a high incidence of hypertension.

In describing the rationale behind CAIRO5, the investigators found that even patients with initially unresectable liver metastases of colorectal cancer, if they had an adequate response to systemic induction therapy, could: Afterwards, they would be eligible for locally curative treatment, such as surgery or local excision, he said.

However, “there is no consensus regarding the optimal induction systemic therapy for patients with early unresectable liver metastases of colorectal cancer,” the researchers wrote. “Furthermore, published data on this patient population indicate that criteria for resectable versus unresectable criteria are non-existent or variable, long-term follow-up of patients receiving local therapy is lacking, study populations, trials Difficult to interpret due to uneven design and usage. RAS/BRAF Mutation status of V600E. ”

Therefore, they wanted to compare the currently most active systemic induction regimens in this setting. They also noted that this was the first study to prospectively compare bevacizumab and anti-EGFR antibodies (both with chemotherapeutic backbones) and considered both. RAS and BRAF V600E mutation status and primary tumor laterality.

The open-label CAIRO5 included 530 patients (median age 62 years, 62% male) enrolled at 46 centers in the Netherlands and 1 center in Belgium.All patients were known histologically to have colorectal cancer RAS/BRAF V600E mutation status, WHO performance status 0–1, and early unresectable colorectal cancer liver metastases.

Resectable or unresectable liver metastases of colorectal cancer are defined in advance by an expert panel of liver surgeons and radiologists at baseline and every 2 months thereafter was evaluated according to

Most patients had synchronous disease and liver metastases from colorectal cancer, which the expert panel considered to be potentially resectable.

From November 2014 to January 2022, patients with a right-sided primary tumor site, or RAS- again BRAF V600E mutant tumors were randomly assigned 1:1 to groups receiving FOLFOX or FOLFIRI plus bevacizumab (n=148) or FOLFOXIRI plus bevacizumab (n=146).left-handed and left-handed patients RAS- and BRAF V600E wild-type tumors were randomized 1:1 to groups receiving FOLFOX or FOLFIRI plus bevacizumab (n=118) or FOLFOX or FOLFIRI plus panitumumab (n=118).

Median follow-up at the time of this analysis was 51.1 months for the first two groups and 49.9 months for the latter two groups.

A limitation of this study was that the use of FOLFOXIRI had not been investigated in patients with left hemi- and left-brain impairment. RAS– and BRAF V600E wild-type tumor.