Neratinib, an irreversible pan-ErbB receptor inhibitor, is highly effective against primary cervical cancer cell lines harboring HER2/neu gene mutations

Abstract

(OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. The associations of smoking and of smoking + treatment (i.e., bevacizumab vs. no bevacizumab) with PFS and OS were evaluated with the Cox proportional hazards model. Results: Smoking questionnaires were available for analysis in 99% of study participants. Two hundred eighty-six women (64%) were active or former smokers. In the entire study population, this group had significantly worse OS than never smokers (14.2 vs. 16.8 months, HR 1.29, 95% CI 1.03–1.61, P= 0.026). Smokers who received chemotherapy plus bevacizumab (n= 148, 52%) experienced significantly longer PFS (median 7.9 vs. 5.7 months, log-rank P b 0.01) and significantly longer OS (median 16.7 vs. 12.0 months, log rank P= 0.027) than smokers who received chemotherapy alone (n= 138, 48%). Overall response rate among smokers was 49.3% (chemotherapy plus bevacizumab) vs. 29% (chemotherapy alone) (P= 0.002). The median number of cycles of therapy was 6 for smokers and nonsmokers (interquartile range, 4–10, smokers vs. 2–9, nonsmokers) (P=ns). Smokers receiving bevacizumab experienced the following adverse events: grade 2+ fistula (16.2%), grade 3+ venous thromboembolism (9.5%), grade 2+hypertension (27%), and grade 2+proteinuria (2.7%). Cervical cancer was the reported cause of death in 74.5% of smokers. Conclusions: Smoking is common and associated with a 29% increased risk of death among women with advanced or recurrent cervical cancer. The survival benefits conferred by antiangiogenesis therapy are sustained, even among smokers in this population. Smokers with CxCA should be informed of these results and efforts at smoking cessation strongly encouraged.