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. 2017 Dec 17;9(2):2876-2886.
doi: 10.18632/oncotarget.23355. eCollection 2018 Jan 5.

Predictive factors for 6 vs 12 cycles of Folfiri-Bevacizumab in metastatic colorectal cancer

Vincenzo Formica  1 , Maria Teresa Ionta  2 , Bruno Massidda  2 , Giacomo Vessia  3 , Luigi Maiorino  4 , Rossana Casaretti  5 , Donato Natale  6 , Giuseppe Barberis  7 , Gianfranco Filippelli  8 , Ettore Greco  9 , Livio Blasi  10 , Sergio Mancarella  11 , Anna Russo  12 , Enrico Barbato  13 , Liberato Di Lullo  14 , Mario Roselli  1
Affiliations

Predictive factors for 6 vs 12 cycles of Folfiri-Bevacizumab in metastatic colorectal cancer

Vincenzo Formica et al. Oncotarget. .

Abstract

Early switching to de-intensified maintenance regimen is still a matter of debate in metastatic colorectal cancer (mCRC). The MARTHA trial, a S.I.C.O.G. phase III randomized trial, compared FOLOFIRI+bevacizumab (B) for 12 cycles (6 months) followed by B for up to 12 months (FOLFIRI +B*12 arm) vs FOLFIRI+B for 6 cycles (3 months) followed by capecitabine+B for 4 cycles followed by B for up to 12 months (FOLFIRI+B*6 arm). Chemotherapy-naïve mCRC patients were randomized, primary endpoint was progression free survival (PFS), with overall survival (OS) as a secondary endpoint. A novel analysis, the Death Pace Analysis (DPA), was performed to identify patients who benefited from a specific treatment. No PFS difference was seen in 198 enrolled patients (101 in FOLFIRI+B*12, 97 in FOLFIRI+B*6). A non-significant superior OS was observed for FOLFIRI+B*6 (HR 0.74, p 0.098). The DPA demonstrated that 14% of patients were identifiable as FOLFIRI+B*6-benefiting patients. According to a logistic regression analysis including 23 clinicopathological variables, baseline Hb was the only independent predictor of DPA-defined FOLFIRI+B*6-benefit status. Among patients with Hb ≤ 11.1 gr/dL a statistically significant prolonged OS was observed for FOLFIRI+B*6 over FOLFIRI+B*12 (median OS: 20.7 vs 12.6 months, respectively, HR 0.54, p 0.048). No survival difference was observed between arms in patients with Hb > 11.1. mCRC patients with low baseline Hb levels are better treated with FOLFIRI+B*6 first-line strategy. Possible biological explanations for this finding are being investigated.

Keywords: bevacizumab; death pace analysis; fluorouracil; irinotecan; metastatic colorectal cancer.

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Conflict of interest statement

CONFLICTS OF INTERESTS No funding or conflicts of interests related to the present work have to be declared.

Figures

Figure 1
Figure 1. CONSORT diagram of MARTHA trial
B: bevacizumab. PS: performance status
Figure 2
Figure 2. Survival analysis and treatment
A. Progression Free Survival (PFS) and B. Overall Survival (OS) curves according to treatment arm. Median PFS was 10.8 and 10.5 months, and median OS was 18.1 and 28.1 months, in FOLFIRI+B*12 and FOLFIRI+B*6 arm, respectively.
Figure 3
Figure 3. Overall survival curves according to treatment arm and primary tumor location
mOS: median overall survival.
Figure 4
Figure 4. Death Pace Analysis of MARTHA trial
A. Overall survival curves as in figure 2B; B. function of the survival probability difference between arms over the time; C. function of the first derivative of survival probability difference between arms over the time.
Figure 5
Figure 5. Survival Analysis and Hemoglobin levels
Overall survival by treatment arm of patients stratified according to Hb ≤ 11.1(A) or Hb >11.1 (B).
See this image and copyright information in PMC

References

    1. Fakih MG. Metastatic colorectal cancer: current state and future directions. J Clin Oncol. 2015;33:1809–24. https://doi.org/10.1200/JCO.2014.59.7633. - DOI - PubMed
    1. Sanz-Garcia E, Grasselli J, Argiles G, Elez ME, Tabernero J. Current and advancing treatments for metastatic colorectal cancer. Expert Opin Biol Ther. 2016;16:93–110. https://doi.org/10.1517/14712598.2016.1108405. - DOI - PubMed
    1. Sepulveda AR, Hamilton SR, Allegra CJ, Grody W, Cushman-Vokoun AM, Funkhouser WK, Kopetz SE, Lieu C, Lindor NM, Minsky BD, Monzon FA, Sargent DJ, Singh VM, et al. Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017;35:1453–86. https://doi.org/10.1200/JCO.2016.71.9807. - DOI - PubMed
    1. Arnold D, Lueza B, Douillard JY, Peeters M, Lenz HJ, Venook A, Heinemann V, Van Cutsem E, Pignon JP, Tabernero J, Cervantes A, Ciardiello F. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomised trials. Ann Oncol. 2017 https://doi.org/10.1093/annonc/mdx175. - DOI - PMC - PubMed
    1. Missiaglia E, Jacobs B, D’Ario G, Di Narzo AF, Soneson C, Budinska E, Popovici V, Vecchione L, Gerster S, Yan P, Roth AD, Klingbiel D, Bosman FT, et al. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol. 2014;25:1995–2001. https://doi.org/10.1093/annonc/mdu275. - DOI - PubMed

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