Tumor Growth Rate After Nadir Is Associated With Survival in Patients With EGFR-Mutant Non–Small-Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

Abstract

PURPOSE To investigate the association between tumor volume growth rate after the nadir and survival in patients with EGFR-mutant advanced non–small-cell lung cancer (NSCLC) treated with erlotinib. MATERIALS AND METHODS Seventy-one patients with EGFR-mutant advanced NSCLC treated with erlotinib were studied for computed tomography tumor volume kinetics during therapy. The tumor growth rate after nadir was obtained using a previously published analytic module for longitudinal volume tracking to study its relationship with overall survival (OS). RESULTS The median tumor volume for the cohort was 19,842 mm3 at baseline and 4,083 mm3 at nadir. The median time to nadir was 6.2 months. The tumor growth rate after nadir for logeV (the natural logarithm of tumor volume measured in mm3) was 0.11/mo on average for the cohort (SE: 0.014), which was very similar to the previously validated reference value of 0.12/mo to define slow and fast tumor growth. The OS of 48 patients with slow tumor growth (≤ 0.12/mo) was significantly longer compared with 23 patients with fast tumor growth (> 0.12/mo; median OS: 37.8 v 25.0 months; P = .0012). In Cox models, tumor growth rate was also associated with survival (regression coefficient: 3.9903; P = .0024; faster rate leads to increased hazards), after adjusting for time to nadir (regression coefficient: –0.0863; P = .0008; longer time to nadir leads to decreased hazards) and smoking history. CONCLUSION In patients with EGFR-mutant advanced NSCLC treated with erlotinib, slower tumor growth rates after nadir were associated with longer OS, providing a rationale for using tumor growth rates to guide precision therapy for lung cancer.

Dissecting sources of variability in patient response to targeted therapy: anti-HER2 therapies as a case study

“…We also found the growth rate of resistance clones, analogous to tumor regrowth rate after progression, to be significant to patient response. Interestingly, growth rate after progression has been directly correlated with patient survival in non-small cell lung cancer and glioblastoma [24], [25]. A similar analysis has been conducted for HER2-negative breast cancer response to chemotherapy [26], though to our knowledge, no such work exists for HER2-positive breast cancer.…”