Retreatment with anti-EGFR based therapies in metastatic colorectal cancer: impact of intervening time interval and prior anti-EGFR response

Abstract

BackgroundThis retrospective study aims to investigate the activity of retreatment with anti-EGFR-based therapies in order to explore the concept of clonal evolution by evaluating the impact of prior activity and intervening time interval.MethodsEighty-nine KRAS exon 2-wild-type metastatic colorectal patients were retreated on phase I/II clinical trials containing anti-EGFR therapies after progressing on prior cetuximab or panitumumab. Response on prior anti-EGFR therapy was defined retrospectively per physician-records as response or stable disease ≥6 months. Multivariable statistical methods included a multiple logistic regression model for response, and Cox proportional hazards model for progression-free survival.ResultsRetreatment anti-EGFR agents were cetuximab (n = 76) or cetuximab plus erlotinib (n = 13). The median interval time between prior and retreatment regimens was 4.57 months (range: 0.46-58.7). Patients who responded to the prior cetuximab or panitumumab were more likely to obtain clinical benefit to the retreatment compared to the non-responders in both univariate (p = 0.007) and multivariate analyses (OR: 3.38, 95 % CI: 1.27, 9.31, p = 0.019). The clinical benefit rate on retreatment also showed a marginally significant association with interval time between the two anti-EGFR based therapies (p = 0.053). Median progression-free survival on retreatment was increased in prior responders (4.9 months, 95 % CI: 3.6, 6.2) compared to prior non-responders (2.5 months, 95 % CI, 1.58, 3.42) in univariate (p = 0.064) and multivariate analysis (HR: 0.70, 95 % CI: 0.43-1.15, p = 0.156).ConclusionOur data lends support to the concept of clonal evolution, though the clinical impact appears less robust than previously reported. Further work to determine which patients benefit from retreatment post progression is needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1701-3) contains supplementary material, which is available to authorized users.

Combined application of anti-VEGF and anti-EGFR attenuates the growth and angiogenesis of colorectal cancer mainly through suppressing AKT and ERK signaling in mice model

“…It has been demonstrated that overexpression of VEGF/EGFR is correlated with the progression and metastasis of CRC [ 32 – 34 ]. Despite that previous studies found the suppressing role of anti-VEGF/EGFR antibody on CRC development [ 35 , 36 ], the potential effect of combination anti-VEGF and anti-EGFR antibodies on CRC growth and angiogenesis remains little known. In this study, we have shown that both increased VEGF and EGFR were associated with hepatic metastases in CRC.…”

First-in-human trial of multikinase VEGF inhibitor regorafenib and anti-EGFR antibody cetuximab in advanced cancer patients

“…The combination was well tolerated and demonstrated clinical benefit in 34% patients with CRC (22). A retrospective review of patients treated with EGFR therapy who progressed and rechallenged supported the notion of anti-EGFR retreatment in metastatic CRC (23).…”

“…All histology was centrally reviewed and molecularly tested at MD Anderson as part of standard of care as previously published (23). Paraffin-embedded tumor sections that were macrodissected were used for DNA extraction.…”

“…KRAS exon 2 (codons 12 and 13) mutations, whenever done were expanded to also report KRAS, NRAS, BRAF V600E, and PIK3CA mutations. This was based on the standard of care testing results done in accordance with the Clinical Laboratory Improvement Amendment (CLIA)-certified lab (23).…”

Treatment of Rectal Cancer-Induced Disseminated Carcinomatosis of the Bone Marrow with FOLFOX plus Cetuximab and Panitumumab

“…The RE-OPEN study demonstrated the effect of reintroduction of oxaliplatin in patients with advanced colorectal cancer previously treated with oxaliplatin and irinotecan [18]. Reintroduction of anti-EGFR antibodies has also been reported to be effective [19,20]. However, effective reintroduction of oxaliplatin and anti-EGFR agents has been limited to patients treated for a duration of 6 months because of discontinuation and reintroduction in these reports.…”