RANDOMISED PHASE II STUDY OF AXITINIB OR BEVACIZUMAB COMBINED WITH PACLITAXEL/CARBOPLATIN PAC/CARB) AS FIRST-LINE THERAPY FOR PATIENTS (PTS) WITH ADVANCED NON–SMALL CELL LUNG CANCER (NSCLC)

Background

Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, with promising single-agent activity in advanced NSCLC. This study evaluated the efficacy and safety of axitinib + pac/carb vs bevacizumab + pac/carb in advanced non-squamous NSCLC.

Methods

Pts with stage IIIB with pleural effusion or stage IV non-squamous NSCLC without prior systemic therapy (except adjuvant therapy >12 mo prior to enrolment) were stratified by prior adjuvant therapy and gender, and randomised 1:1 to receive axitinib (5 mg twice daily) or bevacizumab (15 mg/kg every 3 wks [q3w]) plus pac/carb (200mg/m2/AUC 6 mg/mL x min q3w). The primary endpoint was progression-free survival (PFS).

Results

Pt baseline characteristics in the axitinib (n = 58) and bevacizumab (n = 60) arms were well balanced: 38% were female, 31% vs 30% were current smokers, respectively. Median PFS (95% confidence interval [CI]) was 5.7 mo (4.1–7.5) in the axitinib vs 6.1 mo (4.2–8.7) in the bevacizumab arms (hazard ratio [HR] 1.09, 95% CI 0.68–1.76; 1-sided stratified P = 0.64). Median overall survival (95% CI) was 10.6 mo (7.5–16.4) and 13.3 mo (10.4–17.6), respectively, in the axitinib vs bevacizumab arms (HR 1.12, 95% CI 0.74–1.69; 1-sided stratified P = 0.70). Objective response rates (95% CI) were 29.3% (18.1–42.7) and 43.3% (30.6–56.8) and duration of response was 4.4 and 7.0 mo for the axitinib and bevacizumab arms, respectively. Common treatment-emergent all-causality adverse events (AEs) with axitinib + pac/carb vs bevacizumab + pac/carb, respectively, were diarrhoea (47% vs 34%), alopecia (36% vs 46%), hypertension (43% vs 42%), decreased appetite (43% vs 22%), fatigue (34% vs 39%), nausea (36% vs 32%), and neutropenia (31% vs 27%). Neutropenia was the most common grade 3/4 AE in both treatment arms. More pts in the axitinib arm discontinued treatment due to AEs than in the bevacizumab arm (41% vs 31%, respectively).

Conclusions

Axitinib + pac/carb did not improve efficacy compared with bevacizumab + pac/carb, and was less well tolerated in pts with advanced non-squamous NSCLC.

Disclosure

C. Twelves: I am an advisor/board member for Pfizer and Genentech/Roche, received honorarium from Pfizer, and honorarium from Speaker's Bureau from Genentech/Roche.

S. Popat: I am a consult for Roche and Pfizer and received honoraria from Roche and Pfizer.

P. Bycott: I am a full-time employee of Pfizer Inc and own Pfizer stocks.

A. Niethammer: I am a full-time employee of Pfizer and own Pfizer stocks.

P. De Besi: I am a conusltat for Pfizer Italia Srl.

J.H. Schiller: I am a consultant for Pfizer and Genentech and received grants/research support from Pfizer and Genentech.

All other authors have declared no conflicts of interest.

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