Upfront FOLFOXIRI+bevacizumab followed by fluoropyrimidin and bevacizumab maintenance in patients with molecularly unselected metastatic colorectal cancer.
BACKGROUND
The addition of bevacizumab (BEV) to standard doublet chemotherapy improves outcomes compared with chemotherapy alone in patients with metastatic colorectal cancer (mCRC). The OPAL study examined the effect of BEV+FOLFOXIRI followed by 5FU/LV and BEV maintenance on progression-free survival (PFS) in patients with previously untreated unresectable mCRC.


METHODS
Eligible patients had histologically confirmed mCRC, ECOG performance status ⩽1 and were 18-70 years old. Patients received up to 12 cycles of FOLFOXIRI+BEV q2w (induction phase) followed by up to ⩽40 cycles of 5FU/LV+BEV q2w (maintenance phase). Median PFS was the primary end point; secondary end points included response, OS, secondary resection rate, safety and prognostic value of pharmacogenetic profiling.


RESULTS
Ninety-seven patients were enrolled. Of these, 90 received study medication and formed the safety population: 64 males; median age 58 (range 28-71) years; ECOG performance status 0/1 in 54%/46% patients; and liver only disease in 35 patients. Relative dose intensities were 79-85% for all four drugs. The incidence of adverse events (AEs) was as previously reported and there were no new safety signals. In total, 87 serious AEs occurred in 39 patients (43%). Median PFS was 11.1 months (95% CI 9.4-12.0) and did thus not meet the primary objective of 12 months. Median OS was 32.2 months (95% CI 22.6-36.9). Fifty-two patients were pharmacogenetically profiled.


CONCLUSIONS
FOLFOXIRI+BEV was feasible in this molecularly unselected mCRC patient population, showing a high efficacy in terms of survival, overall response and secondary resection rate. Pharmacogenomic profiling revealed no clinically relevant marker.
University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
Alexander
A
Stein
University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
Djordje
D
Atanackovic
Charité Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, Berlin 10117, Germany.
Bert
B
Hildebrandt
University Hospital Magdeburg, Leipziger Strasse 44, Magdeburg 39120, Germany.
Patrick
P
Stübs
Schwarzwald-Baar Klinikum, Klinikstrasse 11, Villingen-Schwenningen 78052, Germany.
Wolfram
W
Brugger
Marienkrankenhaus, Alfredstrasse 9, Hamburg 22087, Germany.
Gunnar
G
Hapke
MVZ Hämatologie/Onkologie Klinik Dr Hancken, Harsefelder Str. 8, Stade 21680, Germany.
Claus-Christoph
CC
Steffens
Klinikum Stuttgart, Kriegsbergstraße 60, Stuttgart 70174, Germany.
Gerald
G
Illerhaus
Ecron Acunova GmbH, Hahnstrasse 70, Frankfurt 60528, Germany.
Ernst
E
Bluemner
Tumorgenetik Bonn, Maximilianstrasse 28d, Bonn 53111, Germany.
Jan
J
Stöhlmacher
University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
Carsten
C
Bokemeyer
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D011905:Genes, ras; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D012720:Severity of Illness Index
D020533:Angiogenesis Inhibitors; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin