Clinical Research Papers:

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

Vincenzo Formica _, Maria Teresa Ionta, Bruno Massidda, Giacomo Vessia, Luigi Maiorino, Rossana Casaretti, Donato Natale, Giuseppe Barberis, Gianfranco Filippelli, Ettore Greco, Livio Blasi, Sergio Mancarella, Anna Russo, Enrico Barbato, Liberato Di Lullo and Mario Roselli

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Oncotarget. 2018; 9:2876-2886. https://doi.org/10.18632/oncotarget.23355

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Vincenzo Formica1,*, Maria Teresa Ionta2,*, Bruno Massidda2,*, Giacomo Vessia3,*, Luigi Maiorino4,*, Rossana Casaretti5,*, Donato Natale6,*, Giuseppe Barberis7,*, Gianfranco Filippelli8,*, Ettore Greco9,*, Livio Blasi10,*, Sergio Mancarella11,*, Anna Russo12,*, Enrico Barbato13,*, Liberato Di Lullo14,* and Mario Roselli1,*

1 Department of Systems Medicine, Medical Oncology Unit, Tor Vergata University Hospital, Rome, Italy

2 Medical Oncology II, Azienda Ospedaliero, Universitaria di Cagliari, Cagliari, Italy

3 Oncologia Medica, Ospedale Della Murgia, Altamura, Italy

4 Department of Medical Oncology, Napoli, Italy

5 Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”- IRCCS, Naples, Italy

6 Ospedale Civile San Massimo, Pescara, Italy

7 Oncologia Medica, Ospedale Evangelico Villa Betania, Napoli, Italy

8 Ospedale S. Francesco di Paola, Paola CS, Italy

9 Oncologia Medica, P.O. Lamezia Terme, Italy

10 UOC Oncologia Medica, ARNAS Civico, Palermo, Italy

11 Oncologia Medica, Presidio Ospedaliero S Caterina, Galatina, Italy

12 Oncologia Medica, Policlinico “Paolo Giaccone”, Palermo, Italy

13 Oncologia medica, Ospedale “ Moscati “ Aversa, Aversa, Italy

14 Oncologia Medica, Ospedale F. Veneziale, Isernia, Italy

* All authors are part of the S.I.C.O.G. (Southern Italy Cooperative Oncology Group)

Correspondence to:

Vincenzo Formica, email:

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

Received: October 11, 2017 Accepted: December 01, 2017 Published: December 17, 2017


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.

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