Volumetric tumor growth in advanced NSCLC patients (pts) with EGFR mutations during EGFR-TKI therapy: Developing criteria to define slow progression.

Abstract

e19125 Background: EGFR-mutated advanced NSCLC pts treated with EGFR TKI typically progress after an initial tumor response. Most pts continue TKI beyond RECIST progression, and an objective guide for treatment decisions is needed. We analyzed the volumetric tumor growth in these pts as an initial step to develop criteria for slow progression to aid therapeutic decision making. Methods: The study population included 58 advanced NSCLC pts with sensitizing EGFR mutations, treated with first-line single-agent gefitinib or erlotinib between 2002-2011, who had baseline CT showing measurable lung lesion and at least two follow-up CTs while on TKI and experienced volumetric tumor growth. Tumor volume (mm3) of the dominant lung lesion was measured on baseline and all follow-up chest CT scans during therapy, using volume analysis software [Nishino et al. Acad Radiol. 2011]. A total of 405 volume measurements from nadir to the end of TKI therapy or last follow-up, with data closure on 6/1/12, were analyzed in a linear mixed effects model, fitting time as a random effect [Laird and Ware, Biometrics, 1982]. Results: Among 58 pts, 46 (79%) were female, median age was 62 (range: 35-84), 29 (50%) were never-smokers, 53 (91%) were stage IV at diagnosis, and 53 (91%) received erlotinib. The median time on TKI was 15.8 months. The median time to tumor nadir was 6.3 months. A linear mixed effects model was fitted to predict growth of the logarithm of tumor volume (logeV), adjusting for time in months from baseline. The growth rate of logeV, obtained as the regression coefficient for time, was 0.12/month (SE: 0.015; p<0.001; logeV=0.12*months+7.68). The model provided a reference value for the volumetric tumor growth rate in EGFR-mutant NSCLC pts after they have achieved their nadir. Conclusions: Tumor volume analysis defined volumetric tumor growth after the nadir in EGFR-mutant advanced NSCLC pts receiving TKI. This provides a reference value for the tumor growth rate in pts progressing after the nadir on TKI. Based on these data which can be studied in additional cohorts, we are currently developing practical radiographic criteria to help define patients as slow progressors who can safely remain on EGFR TKIs.