Platinum re-treatment as a second-line option for clinically and molecularly defined platinum-sensitive metastatic non-small cell lung cancer (NSCLC).

Abstract

e18032 Background: Despite significant advances in NSCLC therapy during the past decade, platinum (Pl) compounds remain the most important drug class in the metastatic setting. Notably, a subgroup of patients (pts) is particularly sensitive to first-line (FL) Pl-based chemotherapy. For these pts, platinum re-challenge might be an interesting approach in the second-line (SL). Identifying those patients beforehand could be crucial. Methods: We describe a unique cohort of pts that upon FL Pl-based chemotherapy show significantly high disease control rate (DCR) and progression-free interval (PFI) – generally > 6 ms (Pl-sensitive). These pts were re-treated with a Pl-doublet in the SL, mostly comprising the same regimen used in the FL. We also evaluated ERCC1 and XIAP expression as potential biomarkers. Clinical and molecular characteristics were compared to a Pl-non-sensitive group (N=65), with < 6 ms PFI after FL-Pl therapy. Results: 28 pts were re-treated with a Pl-doublet in the SL between 2000 and 2007. This Pl-sensitive group was older than the Pl-non-sensitive group (median age 64 vs 58; P=.004), presented a higher proportion of females (46% vs 28%; P=.08), never-smokers (36% vs 18%; P=.07), and squamous histology (39% vs 19%; P=.04). The DCR (100% vs 27%; P<.0001), and PFI (median 10.7 vs 0.9 ms; P<.0001) were clearly superior in the Pl-sensitive group. Accordingly, the progression-free (median, 12.6 vs 3.3 ms; P<.0001) and overall survival (27.4 vs 6.1 ms; P<.0001) were considerably longer in the Pl-sensitive group. For pts with available tumor samples, the expression of ERCC1 and XIAP in Pl-non-sensitive group was 30% (14/46) and 45% (21/47). In contrast, no expression of ERCC1 or XIAP was observed in the Pl-sensitive - 0/3 (P=.25) and 0/4 (P=.08). Conclusions: A group of clinically selected pts - with high DCR and long PFI after FL - derived great benefit from Pl-therapy also in the SL. The outcomes are in line with SL FDA-approved options, which support further prospective evaluation. ERCC1 and XIAP are evolving biomarkers in this field, and coupled to clinical features here identified may add to patient selection and enhance the benefits from Pl re-treatment strategy.