Second‐line cetuximab/irinotecan versus oxaliplatin/fluoropyrimidines for metastatic colorectal cancer with wild‐type KRAS

Abstract

The goal of the present study was to compare the efficacy of the combination of cetuximab and irinotecan to the combination of oxaliplatin and fluoropyrimidines as second-line chemotherapy in patients with irinotecan-refractory and oxaliplatin-na€ ıve metastatic colorectal cancer (mCRC) harboring wild-type KRAS. The study included 120 patients with mCRC who had progressed after irinotecan-containing first-line chemotherapy and were never treated with oxaliplatin; 40 patients with wild-type KRAS were accrued prospectively in the experimental arm (arm A), and 80 patients accrued retrospectively were divided into control arms B (n = 46) and C (n = 34) according to KRAS genotype. Second-line treatments consisted of cetuximab plus irinotecan for arm A, and oxaliplatin plus either 5-fluorouracil (FOLFOX) or capecitabine (CapeOX) for the control arms. The median progression-free survival (PFS) was 8.3, 5.8 and 3.9 months, for arms A, B and C, respectively, with statistical significance favoring arm A (P = 0.007). Differences in overall survival did not reach statistical significance (18.3 vs 12.6 vs 12.9, P = 0.138), although there was a trend toward longer overall survival in arm A. In terms of benefit from oxaliplatin-containing regimens either as second-line or third-line therapy, the median PFS was 5.0 months in arms B and C as second-line therapy, and 4.0 months in arm A as third-line therapy, with no statistical significance (P = 0.385). Second-line cetuximab plus irinotecan is a valid treatment strategy for mCRC patients with irinotecan-refractory and oxaliplatin-na€ ıve tumors harboring wild-type KRAS. Oxaliplatin-containing chemotherapy resulted in equivalent PFS both as a second-line and a third-line therapy, enabling delay of the administration of FOLFOX and CapeOX until subsequent treatment cycles. (Cancer Sci 2013; 104: 473-480) A t present, a limited number of active drugs are available for the treatment of metastatic colorectal cancer (mCRC), and the upfront doublet combination of fluoropyrimidines plus either oxaliplatin or irinotecan is regarded as the reference strategy for patients for whom intensive therapy is appropriate.(1-3) Before the era of targeted agents, treatment strategies in terms of the combination or sequence of cytotoxic agents were rather simple; survival outcomes did not differ according to either the administration sequence of oxaliplatin or irinotecan, and whether sequential or combination chemotherapy was applied in the treatment continuum was inconsequential.(4-7) Treatment strategies have become more complicated in the era of targeted agents.Bevacizumab plus chemotherapy as initial chemotherapy improved efficacy without significant adverse events and was proven effective as second-line continuation beyond progression; (8)(9)(10)(11)(12) however, limited overall survival (OS) benefit was observed when bevacizumab was combined with optimal doublet chemotherapy.As a first-line treatment, cetuximab has shown OS benefit when combined with irinotecan plus infusional 5-fluorouracil...

Optimising the use of cetuximab in the continuum of care for patients with metastatic colorectal cancer

“…In cetuximab-naïve patients, later-line treatment with cetuximab plus chemotherapy generally results in efficacy benefits over chemotherapy alone. 56 59 Use of cetuximab monotherapy or cetuximab plus chemotherapy in second-line and later-line mCRC does not yield any new safety signals, thereby further supporting its utility. 56 57 59 113 114 …”

“… 56 59 Use of cetuximab monotherapy or cetuximab plus chemotherapy in second-line and later-line mCRC does not yield any new safety signals, thereby further supporting its utility. 56 57 59 113 114 …”

“…Multiple studies with dedicated second-line, third-line or mixed second-line and further-line patient populations have indicated improved survival and ORR with cetuximab monotherapy or cetuximab in combination with chemotherapy 56–62 and with panitumumab monotherapy or panitumumab plus chemotherapy. 57 63–67 Overall, all current guidelines conclude that patients with RAS wt mCRC who do not receive a biologic in the first line (but are fit enough to receive it in later lines) should be considered candidates for an anti-EGFR therapy in the next available line.…”

Pyrosequencing analysis of KRAS codon 61 mutations in Thai patients with advanced colorectal cancer

“…The anti-EGFR can be used as a first-line treatment for patients whose tumors have wild-type KRAS [9,10] or as a second-line for patients who are refractory to chemotherapy [11]. In addition, it can be used solely as a third-line treatment for patients who have failed or been intolerant to chemotherapy [12].…”

Choice of Targeted Drug for Second-Line Metastatic Colon Cancer Chemotherapy

“…Отмечено значимое увеличение медианы времени до прогрессирования в группе иринотекана и цетукси-маба: 8,3 против 5,8 мес (p = 0,007). Также получена тенденция к более высоким показателям медианы продолжительности жизни в группе с цетуксимабом: 18,3 против 12,6 мес (р = 0,138) [6].…”