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. 2018 Dec 28:11:359-368.
doi: 10.2147/CMAR.S183093. eCollection 2019.

Sequential therapy with bevacizumab and EGFR inhibitors for metastatic colorectal carcinoma: a national registry-based analysis

Tomas Buchler  1 , Renata Chloupkova  2 , Alexandr Poprach  3 , Ondrej Fiala  4   5 , Igor Kiss  3 , Katerina Kopeckova  6 , Ladislav Dusek  2 , Veronika Veskrnova  1 , Lubomir Slavicek  7 , Milan Kohoutek  8 , Jindrich Finek  4 , Marek Svoboda  3 , Lubos Petruzelka  9 , Bohuslav Melichar  10
Affiliations

Sequential therapy with bevacizumab and EGFR inhibitors for metastatic colorectal carcinoma: a national registry-based analysis

Tomas Buchler et al. Cancer Manag Res. .

Abstract

Purpose: Although inhibitors of vascular endothelial growth factor and inhibitors of epidermal growth factor receptor (EGFRi) are commonly used for the treatment of metastatic colorectal cancer (mCRC), the optimal sequencing of these agents is currently unclear.

Methods: A national registry of targeted therapies was used to analyze baseline characteristics and outcomes of patients with mCRC and wild-type KRAS exon 2 status who received bevacizumab and EGFRi (cetuximab or panitumumab) as a part of first- and second-line treatment in either sequence.

Results: The cohort included 490 patients (181 patients treated with first-line EGFRi and second-line bevacizumab and 309 patients treated with first-line bevacizumab and second-line EGFRi). Median overall survival (OS) from the initiation on first-line therapy was similar for patients treated with either sequence, reaching 31.8 (95% CI 27.5-36.1) vs 31.4 months (95% CI 27.8-35.0) for EGFRi → bevacizumab vs bevacizumab → EGFRi cohort, respectively. Time from first-line initiation to progression on the second-line therapy [progression-free survival (PFS)] was 21.1 (95% CI 19.3-23.0) vs 19.3 months (95% CI 17.3-21.3) for bevacizumab → EGFRi vs EGFRi → bevacizumab cohort, respectively (P=0.016).

Conclusion: This retrospective analysis of real-world data of patients with wild-type KRAS exon 2 mCRC showed no differences in OS between cohorts treated with bevacizumab → EGFRi vs the reverse sequence while combined PFS favored the bevacizumab → EGFRi sequence.

Keywords: bevacizumab; cetuximab; colorectal carcinoma; panitumumab; sequence.

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Conflict of interest statement

Disclosure TB, OF, and BM have received research funding, travel grants, and honoraria from Roche, Merck, and Amgen. AP has received honoraria and travel grants from Roche and Amgen. IK has received speakers’ honoraria from Roche, Merck, and Amgen. JF has received lecture honoraria and travel grants from Roche, Merck, Pfizer, Novartis, and Amgen. The authors declare no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
CONSORT diagram of selection of patient data from the CORECT database. Abbreviations: EGFR, epidermal growth factor receptor; FOLFIRI, 5-fluorouracil, leucovorin, and irinotecan; FOLFOX, 5-fluorouracil, leucovorin, and oxaliplatin; CONSORT, Consolidated Standards of Reporting Trials.
Figure 2
Figure 2
OS from first-line treatment initiation. Abbreviations: EGFR, epidermal growth factor receptor; OS, overall survival.
Figure 3
Figure 3
Forest plot of OS for selected patient subgroups. Note: Wild-type RAS subgroup includes patient with available result of extended KRAS and NRAS testing. Abbreviations: BMI, body mass index; OS, overall survival.
Figure 4
Figure 4
Time from treatment initiation to progression on second-line treatment. Abbreviations: EGFR, epidermal growth factor receptor; PFS, progression-free survival.
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