Survival versus intrinsic and acquired resistance in advanced non-small cell lung cancer.

Abstract

e19066 Background: While advanced NSCLC responds to platinum-based therapy (PBT), intrinsic and acquired resistance limits efficacy. We assessed impact of resistance patterns on overall survival (OS). Methods: Using serial measurements of tumor diameters from 130 NSCLC patients on PBT, we calculated % incremental change in tumor size compared to the most recent prior scan and % overall change from pre PBT. Results: 98/130 (75%) had measurable tumor shrinkage (TS) at 1st repeat scan (RS) post 2 cycles, of whom 81 had a 2nd RS post 4 cycles. Of these, 20 (25%) had tumor growth (TG) at the 2nd RS. Only 1 had initial TG then followed by TS. Of 41 with a 3rd RS <4 weeks post cycle 6, 13/41 (32%) had TG. The greatest % incremental TS (compared to most recent prior scan) was seen early (at 1st RS) for 76% of patients. Rate of TS decreased with later cycles in these patients. 11 patients had rapid TS on 1st RS, then gradual further shrinkage over >3 subsequent scans, while 15 had progressive gradual TS over >4 scans without initial rapid TS. By Spearman coefficients, maximum % TS from pre PBT over all scans correlated with OS (r=0.46, p<0.0001), time to progression (TTP) (r=0.69, p<0.0001) and post-progression survival (PPS) (r=0.30, p=0.001). TTP also correlated with OS (r=0.63, p<0.0001), TTP correlated with PPS (r=0.44, p<0.0001), and OS correlated with PPS (r=0.95, p<0.0001). Median OS (11.0 months for all patients) varied with TS pattern (p<0.0001): OS for patients with first TG at 1st, 2nd, 3rd and 4th RS was 5.9, 10.8, 10.5 and 15.1 months. OS was 18.2 months in patients with most TS at 1st RS followed by gradual further TS over later scans, and was 30.5 months with progressive gradual TS without rapid TS at 1st RS. OS with RECIST partial response (23% of patients), minor TS (52%), minor TG (13%) and RECIST progressive disease (13%) was 16.9, 12.4, 9.8 and 4.0 months (p<0.0001). Conclusions: OS, TTP and PPS correlate strongly with response (degree of TS/TG) and with resistance pattern. OS is longest with progressive further TS over multiple scans. Within this group, partial acquired resistance (decreased TS rate after initial rapid TS) has shorter OS than with sustained incremental TS. The underlying biological factors driving clinical resistance remain undefined.