Comparison of early radiological predictors of outcome in patients with colorectal cancer with unresectable hepatic metastases treated with bevacizumab.

Objective: The purpose was to validate the prognostic value of an early optimal morphological response on CT in patients treated with bevacizumab-containing chemotherapy for unresectable colorectal cancer liver metastases (CLM). It also evaluated the prognostic value of size-based criteria and the association of optimal morphological response with the receipt of bevacizumab.
Design: 141 patients treated first using bevacizumab and 142 patients from a randomised study evaluating the addition of bevacizumab to oxaliplatin-based chemotherapy were retrospectively analysed. Radiologists evaluated pretreatment and restaging CT scans using morphological response criteria. Responses were also assessed with size-based criteria: Response Evaluation Criteria in Solid Tumors (RECIST), early tumour shrinkage (ETS) and deepness of response (DpR). The ability of each criterion to predict progression-free survival (PFS), overall survival (OS) and postprogression survival (PPS) was determined using a univariate Cox proportional hazards model.
Results: In both populations, median PFS was significantly longer for patients achieving an optimal morphological response (10.4 vs 6.8 months, p=0.03; and 8.3 vs 4.9 months, p<00001, respectively). Neither RECIST nor ETS responses were associated with a prolonged PFS. Median OS was longer for those with an optimal morphological response but only at second restaging in the first population (n=141, 20.8 vs 12.3 months, p=0.002). DpR but not optimal morphological response was associated with PPS. In the randomised study, an optimal morphological response was 6.2 times more likely among patients receiving bevacizumab (p<0.0001).
Conclusion: In patients with unresectable CLM, early morphological response may be a better predictor of PFS than size-based response. The addition of bevacizumab improves morphological response rate.
Competing Interests: Competing interests: TM disclosed research funding from ROCHE; honoraria from AMGEN and SANOFI; and travel, accommodations, expenses paid by AMGEN. SK declared research funding from ROCHE, AMGEN, GSK, SANOFI, SYSMEX, BIOCARTIS, GUARDANT HEALTH and AGENDIA and consulting or advisory role for AMGEN, ROCHE, GSK, JANSSEN, BMS, AGENDIA, MERRIMACK, SYSMEX, BAYER, TAIHO, SANOFI and ARRAY BIOPHARMA. CE declared honoraria from ROCHE, GENENTECH and BAYER; consulting or advisory role for BAYER and SIRTEX; participation in a speakers’ bureau for GENENTECH; and travel, accommodations and expenses paid by GENENTECH, SIRTEX and BAYER. HC disclosed honoraria from NOVARTIS; consulting or advisory role for NOVARTIS; and travel, accommodations and expenses paid by NOVARTIS. MJO declared consulting or advisory role for MERRIMACK and SIRTEX and research funding from ROCHE, AMGEN, BMS, CELGENE, MEDIMMUNE and MERCK. MY disclosed honoraria from ROCHE and consulting and advisory role for ROCHE. J-NV disclosed research funding from ROCHE. All remaining authors have declared no conflicts of interest.
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