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.
- colorectal cancer
- liver metastases
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EML and SK contributed equally.
TM and PB contributed equally.
Contributors TM was the chief investigator and was involved with study design, collection and assembly of data, data analysis and interpretation and manuscript writing. SK was involved with study design, patient recruitment, collection and assembly of data, data analysis and interpretation and manuscript writing. EML and PB were involved with study design, collection and assembly of data, data analysis and interpretation and manuscript writing. DH and MAA were involved with study design, collection and assembly of data and manuscript writing. J-NV was involved with study design, patient recruitment and manuscript writing. HC was involved with study design, collection and assembly of data, data analysis and interpretation. MJO and CE were involved with patient recruitment, collection and assembly of data, data analysis and interpretation and manuscript writing. DMM was involved with patient recruitment, collection and assembly of data and manuscript writing. MY was involved with conception and design, data analysis and interpretation and manuscript writing. All authors reviewed and approved the final manuscript to submit.
Funding This study was sponsored by F Hoffmann-La Roche Ltd, Basel, Switzerland. No grant number is applicable.
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.
Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.
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