Tumor Volume Nadir in Patients With ALK-Rearranged Non–Small-Cell Lung Cancer Treated With Alectinib

Abstract

PURPOSE Patients with oncogene-driven advanced non–small-cell lung cancer (NSCLC) treated with effective targeted therapy demonstrate characteristic tumor volume dynamics with initial response, nadir, and subsequent regrowth. This study investigated tumor volume nadir and time to nadir in patients with ALK-rearranged advanced NSCLC treated with alectinib. MATERIALS AND METHODS In patients with advanced ALK-rearranged NSCLC treated with alectinib monotherapy, tumor volume dynamics were evaluated on serial computed tomography (CT) scans using a previously validated CT tumor measurement technique. A linear regression model was built to predict tumor volume nadir. Time-to-event analyses were performed to evaluate time to nadir. RESULTS Among 45 patients who experienced initial volume decrease, 37 patients (25 with tumor regrowth and 12 without regrowth but >6 months follow-up) were studied for nadir volume (Vp). The linear model to predict tumor volume nadir was built using the baseline tumor volume (V0): V0-Vp = .696 × V0 + 5,326 ( P < 2 × 10−16; adjusted R2 = 0.86). The percent volume changes at nadir (median, −90.9%, mean, −85.3%) showed larger decrease in patients who were treated with alectinib as first-line therapy than in the ≥2nd-line group and were independent of V0 and clinical variables. Time to nadir had a median of 11.5 months and was longer in the first-line group ( P = .04). CONCLUSION The tumor nadir volume in patients with ALK-rearranged advanced NSCLC treated with alectinib can be predicted by the liner regression model and consists of approximately 30% of the baseline volume minus 5 cm3, providing additional insights into precision therapy monitoring and potential guides for local ablative therapy to prolong disease control.

Alk-rearranged lung adenocarcinoma: From molecular genetics to therapeutic targeting

“…35 ALK-rearranged LUAD patients treated with alectinib usually exhibit a characteristic tumor volume dynamic with initial response with tumor volume decrease, nadir and subsequent regrowth; the percent tumor volume changes, evaluated by serial computed tomography, induced by alectinib at nadir (-90.9%) were more pronounced in patients who were treated as first-line, compared to those treated in second-line. 36…”