Oligo-residual disease in metastatic ALK-positive NSCLC treated with alectinib

Accumulating evidence suggests local consolidative therapy may delay resistance and benefit metastatic NSCLC patients with oligo-residual disease (ORD) after effective systemic therapy. However, the incidence and clinical features of ORD in Alectinib-treated metastatic ALK-positive NSCLC remain unclear. We retrospectively reviewed serial scans of metastatic ALK-positive NSCLC patients treated with Alectinib. ORD was defined as the presence of five or fewer residual metastatic lesions (including the primary site) among those developed partial response as the best response after Alectinib treatment. Initial patterns of recurrence were classified as involving only residual-site recurrence (RR), only new-site recurrence (NR), or a combination of both (RNR). Among 128 patients, 62 patients had PR as the best response, among whom 18 (29.0%) had ORD. The median time to tumor volume nadir was 4.9 (range, 1.1-19.2) months and no independent predictor of ORD was found. To date, 50.0% (9/18) patients with ORD developed their initial progressive disease (PD), mostly (5, 55.6%) with only residual sites. Among the 9 PD patients, 6 patients (6/9, 66.7%) with brain lesions at baseline. Half (3/6, 50.0%) were involved in only brain residual sites. Our study found ORD is not rare in Alectinib treated ALK-positive NSCLC, with 55.6% having initial PD at originally involved sites. Similar recurrence pattern is also observed in PD patients with baseline BMs. These findings indicate that residual disease may enable the emergence of acquired resistance in both CNS and other organs, thus supporting potential clinical benefits for LCT in these ORD patients. Clinical trial number Not applicable.