CHICAGO — Weekly paclitaxel plus bevacizumab significantly improved progression-free survival and objective response rate compared with docetaxel as second- or third-line therapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC), data presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting suggest.1
“In breast and ovarian cancers, adding bevacizumab to paclitaxel improved objective response rate and progression-free survival,” said lead investigator Alexis B. Cortot, MD, thoracic oncologist at Lille University Hospital in France. “In non-squamous NSCLC, adding bevacizumab and carboplatin as first-line therapy improved progression-free survival and overall survival.”
The addition of bevacizumab to weekly paclitaxel has demonstrated synergism and increased activity in various tumor types. Consequently, researchers assessed the combination with docetaxel as second- or third-line treatment for advanced non-squamous NSCLC.
For the phase 3 ULTIMATE trial, investigators enrolled 166 patients who progressed after 1 or 2 lines of treatment, including platinum-based chemotherapy. Patients were randomly assigned 2:1 to receive paclitaxel 90 mg/m2 IV on days 1, 8, and 15 plus bevacizumab 10 mg/kg IV on days 1 and 15 of each 28-day cycle or docetaxel monotherapy 75 mg/m2 IV on day 1 of each 21-day cycle until disease progression. Patients who progressed were eligible to cross over to the other study arm.
Results showed that at a median follow-up of 28.9 months, median progression-free survival was 5.4 months (95% CI, 4.6-7.1) with chemoimmunotherapy compared with 3.9 months (95% CI, 2.7-5.3) with docetaxel (HR, 0.62; 95% CI, 0.44-0.87; P=.006). Importantly, efficacy with paclitaxel plus bevacizumab was observed regardless of number of previous treatment lines.
Researchers also found that objective response rate at 8 weeks was 22.5% (95% CI, 14.8-30.3) with weekly paclitaxel and bevacizumab vs 5.5% (95% CI, 0.0-11.5) with docetaxel (P=.006); however, there was no significant difference in median overall survival between the 2 treatment arms (HR, 1.18; P=.40).
“Weekly paclitaxel and bevacizumab demonstrated superiority over docetaxel for objective response rate and progression-free survival, with a 38% reduction in risk of progression,” Dr Cortot explained.
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Grade 3 to 4 adverse events occurring during the first sequence of treatment were comparable between the 2 groups (45.9% with paclitaxel plus bevacizumab vs 54.5% with docetaxel). Docetaxel treatment was significantly more associated with grade 3 to 4 neutropenia and febrile neutropenia, while grade 3 to 4 neuropathy and hypertension were more frequently reported with the combination. The study further showed that the combination preserved quality of life.
“The phase 3 trial ULTIMATE introduces weekly paclitaxel and bevacizumab as a new treatment option in second- or third-line therapy for non-squamous NSCLC patients,” Dr Cortot concluded.
- Cortot AB, Audigier-Valette C, Molinier O, et al. Weekly paclitaxel plus bevacizumab versus docetaxel as second or third-line treatment in advanced non-squamous non-small cell lung cancer (NSCLC): Results from the phase III study IFCT-1103 ULTIMATE. J Clin Oncol. 2016; 34 (suppl; abstr 9005).