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Surgical treatment options following chemotherapy plus cetuximab or bevacizumab in metastatic colorectal cancer—central evaluation of FIRE-3

Published:November 28, 2017DOI:https://doi.org/10.1016/j.ejca.2017.10.028

      Highlights

      • We report a central review for resectability of 448 patients with metastatic colorectal cancer receiving first-line therapy (FIRE-3 trial).
      • Twenty-two percent of the patients before systemic therapy and 53% of the patients at best response were considered candidates for resection.
      • Actual reported resectability was 16% in the evaluated cohort.
      • Actual resection rates were significantly associated with treatment context (university hospital versus other hospitals/practices).

      Abstract

      Background

      The FIRE-3 trial investigated combination chemotherapy plus either cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer (mCRC) not scheduled for upfront surgery. We aimed to determine the number of patients who present with potentially resectable disease during systemic first-line therapy and to compare the findings with study reports concerning resections and outcome.

      Patients and methods

      This evaluation of 448 patients was performed as central review blinded for treatment, other reviewers' evaluations and conducted interventions. Resectability was defined if at least 50% of the reviewers recommended surgical-based intervention. Overall survival was assessed by Kaplan–Meier method.

      Results

      Resectability increased from 22% (97/448) at baseline before treatment to 53% (238/448) at best response (P < 0.001), compared with an actual secondary resection rate for metastases of 16% (72/448). At baseline (23% versus 20%) and best response (53% versus 53%), potential resectability of metastases in this molecular unselected population was similar in cetuximab-treated patients versus bevacizumab-treated patients and not limited to patients with one-organ disease. The actual resection rate of metastases was significantly associated with treatment setting (P = 0.02; university hospital versus hospital/practice). Overall survival was 51.3 months (95% confidence interval [CI] 35.9–66.7) in patients with resectable disease who received surgery, 30.8 months (95% CI 26.6–34.9) in patients with resectable disease without surgery and 18.6 months (95% CI 15.8–21.3) in patients with unresectable disease (P < 0.001).

      Conclusions

      Our findings illustrate the potential for conversion to resectability in mCRC, certain reluctance towards metastatic resections in clinical practice and the need for pre-planned and continuous evaluation for metastatic resection in high-volume centres.

      ClinicalTrials.gov-identifier

      NCT00433927.

      Keywords

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      References

        • National Comprehensive Cancer Network
        Clinical practice guidelines in oncology (NCCN Guidelines®) colon cancer version 2.2016.
        2016
        • Abdalla E.K.
        • Bauer T.W.
        • Chun Y.S.
        • et al.
        Locoregional surgical and interventional therapies for advanced colorectal cancer liver metastases: expert consensus statements.
        HPB (Oxford). 2013; 15: 119-130
        • Van Cutsem E.
        • Cervantes A.
        • Adam R.
        • et al.
        ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.
        Ann Oncol. 2016; 27: 1386-1422
        • Adam R.
        • Delvart V.
        • Pascal G.
        • et al.
        Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival.
        Ann Surg. 2004; 240 (discussion 657–648): 644-657
        • Patel D.
        • Townsend A.R.
        • Karapetis C.
        • et al.
        Is survival for patients with resectable lung metastatic colorectal cancer comparable to those with resectable liver disease? Results from the South Australian Metastatic Colorectal Registry.
        Ann Surg Oncol. 2016; 23: 3616-3622
        • Abbas S.
        • Lam V.
        • Hollands M.
        Ten-year survival after liver resection for colorectal metastases: systematic review and meta-analysis.
        ISRN Oncol. 2011; 2011763245
        • Abdalla E.K.
        • Adam R.
        • Bilchik A.J.
        • et al.
        Improving resectability of hepatic colorectal metastases: expert consensus statement.
        Ann Surg Oncol. 2006; 13: 1271-1280
        • Carpizo D.R.
        • D'Angelica M.
        Liver resection for metastatic colorectal cancer in the presence of extrahepatic disease.
        Lancet Oncol. 2009; 10: 801-809
        • Nordlinger B.
        • Sorbye H.
        • Glimelius B.
        • et al.
        Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial.
        Lancet Oncol. 2013; 14: 1208-1215
        • Folprecht G.
        • Gruenberger T.
        • Bechstein W.O.
        • et al.
        Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial.
        Lancet Oncol. 2010; 11: 38-47
        • Ychou M.
        FOLFIRINOX combined to targeted therapy according RAS status for colorectal cancer patients with liver metastases initially non-resectable: a phase II randomized study—Prodige 14 – ACCORD 21 (METHEP-2), a unicancer GI trial.
        J Clin Oncol. 2016; 34 (suppl; abstr 3512)
        • Loupakis F.
        • Cremolini C.
        • Masi G.
        • et al.
        Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer.
        N Engl J Med. 2014; 371: 1609-1618
        • Venook A.P.
        CALGB/SWOG 80405: analysis of patients undergoing surgery as part of treatment strategy.
        Ann Oncol. 2014; 25 (abstr LBA10): v1-v4
        • Venook A.P.
        • Niedzwiecki D.
        • Lenz H.J.
        • et al.
        Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: a randomized clinical trial.
        JAMA. 2017; 317: 2392-2401
        • Schwartzberg L.S.
        • Rivera F.
        • Karthaus M.
        • et al.
        PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer.
        J Clin Oncol. 2014; 32: 2240-2247
        • Heinemann V.
        • von Weikersthal L.F.
        • Decker T.
        • et al.
        FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial.
        Lancet Oncol. 2014; 15: 1065-1075
        • Modest D.P.
        • Stintzing S.
        • von Weikersthal L.F.
        • et al.
        Impact of subsequent therapies on outcome of the FIRE-3/AIO KRK0306 trial: first-line therapy with FOLFIRI plus cetuximab or bevacizumab in patients with KRAS wild-type tumors in metastatic colorectal cancer.
        J Clin Oncol. 2015; 33: 3718-3726
        • Stintzing S.
        • Modest D.P.
        • Rossius L.
        • et al.
        FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial.
        Lancet Oncol. 2016; 17: 1426-1434
        • Light R.J.
        Measures of response agreement for qualitative data: some generalizations and alternatives.
        Psychol Bull. 1971; 76: 365-377
        • Choti M.A.
        • Thomas M.
        • Wong S.L.
        • et al.
        Surgical resection preferences and perceptions among medical oncologists treating liver metastases from colorectal cancer.
        Ann Surg Oncol. 2016; 23: 375-381
        • de Haas R.J.
        • Wicherts D.A.
        • Flores E.
        • et al.
        R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery?.
        Ann Surg. 2008; 248: 626-637
        • Luo L.X.
        • Yu Z.Y.
        • Huang J.W.
        • Wu H.
        Selecting patients for a second hepatectomy for colorectal metastases: an systemic review and meta-analysis.
        Eur J Surg Oncol. 2014; 40: 1036-1048
        • Adams R.B.
        • Aloia T.A.
        • Loyer E.
        • et al.
        Selection for hepatic resection of colorectal liver metastases: expert consensus statement.
        HPB (Oxford). 2013; 15: 91-103
        • Karoui M.
        • Penna C.
        • Amin-Hashem M.
        • et al.
        Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases.
        Ann Surg. 2006; 243: 1-7