Second line FOLFOX4 and bevacizumab for metastatic colorectal cancer: Real life efficacy and predictive factors
Authors: T. Lewandowski, R. Biernacka, M. Chmielowiec, M. Gryziak
Journal: Annals of Oncology (2018)

Introduction: Bevacizumab with chemotherapy is one of valid options in second line treatment for patients with mCRC. According to clinical trials it improves overall survival (OS) and time to progression (TTP) for approximately 2 and 2.5 months compared to chemotherapy alone. However, it is still uncertain what predictive and prognostic factors are useful to select patient who may benefit from that therapy. Methods: We analysed 82 unselected patients treated between 2012-2015 in single-institution with FOLFOX4 regimen and bevacizumab after first-line treatment with FOLFIRI. All of them presented ECOG 0-1. None of them was previously treated with bevacizumab, oxaliplatin or anti-EGFR. The RECIST 1.1 criteria were used to evaluate treatment response. Following factors were investigated to have impact on response rate (ORR), TTP, and OS: RAS (KRAS/NRAS) mutational status, primary tumour location and metastases site, efficacy of first-line treatment, sex, age, body mass index, lactate dehydrogenase (LDH), alkaline phosphatase, CEA, lymphocytes and haemoglobin level at the time of beginning second line treatment. Median follow-up was 35 months. Results: In whole group median TTP was 5.1 months and OS – 12.9. Response rates: CR -1%, PR – 18%, NC – 40%, PD – 40%. For patients who achieved ORR (CR or PR) median TTP and OS was 7.8 and 19.3 months while for patients with PD – 2.8 and 9.9. Hepatic location of metastases was associated with the highest rate of ORR, while peritoneal with the lowest: 46% and 0% (p = 0.041) respectively. Median TTP for patients who gained CR, PR or NC (DCR - disease control) while first-line treatment was 6.7 compared with 3.3 months for patients with PD (p < 0,0001). TTP under/equal 6 months and PD during first-line treatment were associated with shorter OS: 12.9 vs 15.3 months (p = 0.049) and 9.9 vs 14.2 months (p = 0.007). Age over 70 and BMI ≥25 were good prognostic factors with OS 19.6 months vs 10.4 (p = 0.01) and 18.4 months vs 9.1 (p = 0.039) respectively. There was no difference between patients in terms of KRAS and NRAS mutational status. For wild type and mutant tumours it was 6.6 months vs 6.1 (p = 0.098) and 17.9 vs 12.9 (p = 0.183) respectively in TTP and OS. Right-side primary tumours were associated with worse DCR, TTP and OS compared to left-side primary; 45%, 2.3 months and 11.2 months vs 61%, 4.9 months and 12.8 months, but the differences were not statistically significant. Other factors did not occur relevant. Sixteen patients (20%) discontinued treatment due to adverse events. There were no toxic deaths. Conclusion: Positive prognostic impact on second-line treatment with bevacizumab and FOLFOX4 in mCRC have: first-line treatment response, hepatic site of metastases, age over 70 and BMI ≥25. Worse prognosis was observed in group of patients with peritoneal metastases and poor response for first-line chemotherapy. RAS mutational status seemed to not influence prognosis in the analysed cohort. Location of the primary tumour in the right side of the colon was not proven to be a negative prognostic factor.