Clinical Research Papers:

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

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.