Tumor volume dynamics and tumor growth rate in ALK-rearranged advanced non-small-cell lung cancer treated with crizotinib

Abstract Purpose The purpose of the study is to investigate volumetric tumor burden dynamics and tumor growth rates in ALK-rearranged advanced NSCLC patients during crizotinib monotherapy. Methods The study included 44 ALK-rearranged advanced NSCLC patients treated with crizotinib monotherapy as their initial ALK-directed therapy, who had at least one measurable lung lesion and at least two follow-up CT scans, and experienced tumor volume increase while on crizotinib. The tumor volume (in mm3) of the dominant lung lesion was measured on serial CT scans during therapy for analysis of tumor growth rates after the volume nadir. Results A total of 231 volume measurements from the nadir to the end of crizotinib therapy or the last follow-up in 44 patients were analyzed in a linear mixed-effects model, fitting time (in months since baseline) as a random effect. When measured from the volume nadir, the tumor growth rate of the logarithm of tumor volume (logeV) was 0.04/month (SE = 0.012, P=0.0011) in the unadjusted model. When adjusted for the baseline volume (logeV0), the growth rate was again 0.04/month (SE = 0.011, P=0.0004). When adjusted for clinical variables and logeV0, the growth rate was 0.045/month (SE = 0.012, P=0.0002), indicating that the tumor growth rate after nadir in this cohort remains very close to 0.04/month regardless of logeV0 or clinical factors. Conclusions Tumor volume growth rate after nadir in ALK-rearranged NSCLC patients treated with crizotinib was obtained, providing objective reference values that can inform physicians when deciding to keep their patients on ALK directed therapy with slowly progressing lung cancer.