Effectiveness of bevacizumab added to standard chemotherapy in metastatic colorectal cancer: final results for first-line treatment from the ITACa randomized clinical trial.
BACKGROUND
We report the results from a first-line phase III randomized clinical trial on metastatic colorectal cancer (mCRC) aimed at evaluating the effectiveness of adding bevacizumab (B) to standard first-line chemotherapy (CT).


METHODS
mCRC patients were randomized to receive first-line CT (FOLFIRI or FOLFOX4) plus B (arm A) or CT only (arm B). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), response rate (ORR) and safety. Three hundred and fifty patients and 310 events were required to have an 80% statistical power to detect a difference in PFS between the groups.


RESULTS
Between November 2007 and March 2012, 376 patients were randomized. About 60% of patients received FOLFOX4 and 40% FOLFIRI. After a median follow-up of 36 months, 343 progressions and 275 deaths had been observed in the overall population. The median PFS was 9.6 [95% confidence interval (CI) 8.2-10.3] and 8.4 (95% CI 7.2-9.0) months for arms A and B, respectively, with a hazard ratio of 0.86 (95% CI 0.70-1.07; P = 0.182). No statistically significant differences in OS or ORR were observed. B-containing regimens were associated with more frequent hypertension, bleeding, proteinuria and asthenia.


CONCLUSIONS
The addition of B to standard first-line CT for mCRC did not provide a benefit in terms of PFS, OS or ORR. Further research is warranted to better identify the target population.


BACKGROUND
NCT01878422.
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori. Electronic address: alessandro.passardi@irst.emr.it.
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A
Passardi
Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola.
O
O
Nanni
Department of Oncology, Per gli Infermi Hospital, Rimini.
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Tassinari
Oncology Unit, S. Maria delle Croci Hospital, Ravenna.
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Turci
Medical Oncology Unit, Guglielmo da Saliceto Hospital, Piacenza.
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L
Cavanna
Oncology Unit, University Hospital of Modena and Reggio Emilia, Modena.
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A
Fontana
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori.
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S
Ruscelli
Medical Oncology Unit, Ramazzini Hospital, Carpi.
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C
Mucciarini
Medical Oncology Unit, Vito Fazzi Hospital, Lecce; Department of Medical Oncology, Istituto Tumori, Bari, Italy.
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V
Lorusso
Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola.
A
A
Ragazzini
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori.
G L
GL
Frassineti
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori.
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Amadori
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
bevacizumab; chemotherapy; metastatic colorectal cancer; randomized clinical trial