Óscar Gerardo Arrieta Rodríguez

LBA109 Background: Options for advanced non-SQ NSCLC patients (pts) who progress after platinum-based doublet chemotherapy (PT-DC) are limited, with minimal improvement in overall survival (OS). We report results from a randomized, global phase III study of NIVO, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC and tyrosine kinase inhibitor, if eligible. Methods: Pts were randomized to NIVO 3 mg/kg Q2W (n=292) or DOC 75 mg/m2 Q3W (n=290) until progression or discontinuation due to toxicity/other reasons. Primary objective was OS; Secondary objectives were investigator-assessed objective response rate (ORR; per RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression, quality of life, and safety. Results: NIVO demonstrated superior OS (HR=0.73; 96% CI: 0.59, 0.89; P=0.00155) and improved ORR (19.2% vs 12.4%; P=0.0235). HR for PFS was 0.92 (95% CI: 0.77, 1.11; P=0.393). PD-L1 expression was associated with benefit from NIVO (Table). In PD-L1+ pts, NIVO showed improved efficacy across all endpoints at predefined 1%, 5%, and 10% cut- points. Grade 3–5 drug-related AEs occurred in 10.5% (30/287) of NIVO and 53.7% (144/268) of DOC pts. No deaths were related to NIVO vs 1 DOC-related death. After discontinuation, 42.1% of NIVO and 49.7% of DOC pts received subsequent systemic therapy. Conclusions: NIVO demonstrated superior OS vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC. The safety profile of NIVO 3 mg/kg Q2W was favorable vs DOC. NIVO demonstrated survival benefit across histologies in two randomized phase III trials. Clinical trial information: NCT01673867. [Table: see text]

PURPOSE: Free plasma RNA has been scarcely studied in patients with cancer. Here we examine the presence of RNA from epithelial tumors in plasma from a series of breast cancer patients and its correlation with tumor characteristics and circulating tumor cells. EXPERIMENTAL DESIGN: beta-actin mRNA was analyzed to check the viability of plasma RNA in samples from 45 patients with breast cancer and 25 controls. Nested primers were used to detect the presence of cytokeratin 19 (CK19) and Mammaglobin in the same samples. Eleven clinicopathological parameters were studied and correlated with molecular parameters. Additionally, we looked for circulating tumor cells in 16 of these patients and in 10 of the controls. RESULTS: All samples showed detectable quantities of beta-actin RNA. In controls, 3 cases (12%) were positive for Mammaglobin, and 5 (20%) were positive for CK19 RNA; of the 45 patients, 27 cases (60%) were positive for Mammaglobin, and 22 (49%) were positive for CK19. These differences were statistically significant (P = 0.001). Tumor size (P = 0.01) and proliferative index (P = 0.02) were associated with the presence of Mammaglobin, CK19, or both RNAs in plasma. Pathological stage (P = 0.06) was close to significance. Although a statistical relationship was not demonstrated, 9 of the 10 patients with circulating tumor cells showed epithelial mRNAs in plasma. CONCLUSIONS: We conclude that epithelial tumor RNA is detectable in plasma from breast cancer patients and that this finding is associated with a probable poor prognosis and circulating tumor cells.

LBA109 The full, final text of this abstract will be available at abstracts.asco.org at 2:00 PM (EDT) on Friday, May 29, 2015, and in the Annual Meeting Proceedings online supplement to the June 20, 2015, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.

9012 Background: Low BRCA1 mRNA levels correlate with longer progression free survival (PFS) in erlotinib treated EGFR mutant NSCLC patients (p), while risk of shortened PFS was associated with intermediate/high BRCA1 levels (HR, 8.46; P<0.0001). We explored the combination of the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib with gefitinib in EGFR mutant NSCLC p. In a previous phase 1 trial, the safety of the combination was confirmed. Recommended phase 2 dose (RP2D) is gefitinib, 250 mg daily, and olaparib, 200 mg thrice daily. Methods: Stage IV treatment naïve NSCLC p with centrally confirmed EGFR mutations and measurable disease were recruited in the study (NCT01513174). We randomly allocated p (1:1) to receive gefitinib 250 mg daily or the combination at the RP2D. The primary endpoint was PFS. PFS related to BRCA1 mRNA was a secondary endpoint, and 53BP1 and enhancer of zeste homolog 2 (EZH2) were analyzed as modulators of BRCA1, overall survival (OS), response rate (RR), safety and tolerability. Target accrual was 186 p. This sample provided 80% power to detect HR of 0.63 after 116 PFS events. The first PFS analysis, side effect profile and RR had a February 28th, 2018 cut-off, minimum follow-up of 18 months (mo). Results: Of the 182 p who underwent randomization, 91 received gefitinib and 91 received gefitinib+olaparib, with no differences in gender, age, never smoker, performance status, bone or brain metastases or EGFR mutation. Median PFS for exon 19 deletions and exon 21 L858R EGFR mutations was 10.4 mo for gefitinib group and 12.8 mo for gefitinib + olaparib group (HR for disease progression or death, 0.83; P=0.329). RR was 68% in gefitinib group and 78% in gefitinib + olaparib group. Conclusions: The gefitinib+olaparib combination did not provide significant benefit over gefitinib alone. Median PFS was 2.4 mo longer for the combination and risk of disease progression or death was 17% lower with gefitinib+olaparib than gefitinib alone. The pre-specified assessment of BRCA1, 53BP1 and EZH2 could determine if a subgroup of p might obtain major benefit from the combination. Clinical trial information: NCT01513174.