Colorectal cancer treatment: FOLFOXIRI + panituzumab vs. FOLFOX + panitumab

The triple regimen failed to improve response or survival and was more
toxic.

Standard first-line chemotherapy for metastatic colorectal cancer includes modified FOLFOX or FOLFIRI plus bevacizumab or epidermal growth factor receptor (EGFR) targeted agents for patients with the left primary of RAS wild-type without BRAF V600E
mutations.
Studies have shown that initial treatment with the triple regimen FOLFOXIRI + bevacizumab improves response rates and survival compared with dual chemotherapy (J Clin Oncol 2020; 38:3314）
。

Italian researchers conducted a randomized phase 3 trial of patients with advanced RAS and BRAF wild-type colorectal cancer that compared dual mFOLFOX + panitumab with triple mFOLFOXIRI + panitumab
.
The median age of the 435 patients was 59 years, 4% had received adjuvant therapy, 47% had the primary resected, and 88% had the left primary lesion
.

At a median follow-up of 26.
5 months, there was no difference in all treatment outcomes between triple regimen and dual regimen, including objective response rate for the primary endpoint (73%~76%; odds ratio, 0.
87; P = 0.
526), progression-free survival (median, 12.
7 and 12.
3 months; hazard ratio, 0.
88; P = 0.
277), and eventual resection of metastases R0 (25% and 29%; Odds ratio, 0.
81; P=0.
317).

In patients with the left primary lesion, there was no difference in response rates between dual and triple therapy (odds ratio, 1.
07).

mFOLFOXIRI was more toxic, with higher rates of grade 3/4 neutropenia (32% vs.
20%), diarrhoea (23% vs.
7%), and rash (29% vs.
19%), as well as more treatment-related deaths (3 vs.
0).

The trial showed no advantage
of triple mFOLFOXIRI+ panitumab versus dual mFOLFOX+ panitumab treatment for patients with wild-type advanced colon cancer with RAS and BRAF.
The trial is clinically significant in suggesting that triple therapy is not meaningful in these patients, including patients with left-sided primary and those considering
eventual metastasectomy.

Articles that are commented on

Rossini D et al.
Upfront modified fluorouracil, leucovorin, oxaliplatin, and irinotecan plus panitumumab versus fluorouracil, leucovorin, and oxaliplatin plus panitumumab for patients with RAS/BRAF wild-type metastatic colorectal cancer: The phase III TRIPLETE study by GONO.
J Clin Oncol 2022 Sep 1; 40:2878.
(https://doi.
org/10.
1200/jco.
22.
00839)