A multicenter phase II study of docetaxel, oxaliplatin, and bevacizumab in first-line therapy for unresectable locally advanced or metastatic non-squamous cell histology non-small-cell lung cancer (NSCLC).
BACKGROUND
Platinum-based doublets are standard of care for advanced non-small-cell lung cancer (NSCLC). The combination of docetaxel and oxaliplatin has shown acceptable toxicity and encouraging activity. This phase II study aimed to determine the safety and efficacy of this doublet with bevacizumab as first-line treatment for stage IIIB/IV NSCLC.


METHODS
Newly diagnosed patients ≥18 years with histologically proven non-squamous NSCLC and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2 received six 21-day cycles of docetaxel, oxaliplatin, and bevacizumab followed by single-agent bevacizumab for a total of 1 year. Primary efficacy end point was radiographically documented progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), time to treatment failure, and safety.


RESULTS
Fifty-three patients were enrolled. Median age was 62.0 years, 71.7 % male, 79.2 % Caucasian. A total of 88.7 % had stage IV or recurrent disease; 94.3 % adenocarcinoma; and 94.3 % ECOG PS 0 or 1. Efficacy results are as follows: median PFS 5.6 months, ORR 30.2 % (complete response 1.9 %, partial response 28.3 %); 37.7 % stable disease; and OS 14.0 months. At least one adverse event (AE) was reported in all patients (n = 52); 98.1 % of AEs were treatment related. The most common treatment-emergent grade ≥3 AEs were neutropenia (15.4 %), diarrhea (13.5 %), and fatigue (11.5 %). A serious AE was present in 32.7 %; the most common were pneumonia (7.7 %) and abdominal pain (5.8 %). Dehydration, diarrhea, febrile neutropenia, sepsis, and supraventricular tachycardia each occurred in 3.8 %.


CONCLUSIONS
The addition of bevacizumab to docetaxel/oxaliplatin is effective with an acceptable safety profile in patients with chemotherapy-naïve advanced NSCLC.
Thoracic Oncology Program, Memorial Cancer Institute, Memorial Health Care System, 801 N. Flamingo Road, Suite 11, Pembroke Pines, FL, 33028, USA, lraez@mhs.net.
Luis E
LE
Raez
Edgardo S
ES
Santos
R Timothy
RT
Webb
James
J
Wade
Roger A
RA
Brito
Melissa
M
Karr
Andra
A
Kennah
Barrett H
BH
Childs
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D000077143:Docetaxel; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D060046:Maintenance Chemotherapy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D043823:Taxoids; D000077150:Oxaliplatin; D000077143:Docetaxel; D000068258:Bevacizumab