No abstract

e20678 Background: Next-generation sequencing (NGS) is beneficial to precision medicine. However, it remains elusive whether the epidermal growth factor receptor ( EGFR) mutant allele frequency (MAF) tested by NGS is predictive for tyrosine kinase inhibitors (TKIs) therapy in advanced non-small-cell lung cancer (NSCLC). Methods: We enrolled 194 advanced NSCLC EGFR mutant patients receiving erlotinib or gefitinib orally. A total of 196 baseline tissue samples from a phase III clinical trial (CTONG 0901; clinicaltrials.gov No.NCT01024413) between July 2009 and 2014 were analyzed by a panel of 168 lung cancer-related genes NGS. The median EGFR MAF was 25.8% (range, 1.4%-86.2%). Patients were divided into MAF low group (1.4%-25.8%) and high group (25.8%-86.2%). We defined PFS as the time of randomization to confirmed disease progression or death from any cause. OS was calculated from randomization to the last visit or death from any cause. Tumor response was assessed by investigators according to RECIST version 1.1. Survival was estimated using the Kaplan-Meier method. The relationship between the response of TKIs and EGFR MAF were evaluated by Pearson Chi-square test or Fisher’s exact test. Results: The median age was 58.7 years (range,31.2- 85.1), 92 (47.4%) were male, 41(21.1%) were smokers,189 (97.4%) had adenocarcinoma, 105 (54.1%) patients were identified as carrying EGFR exon 19 deletion, while one patient with the co-existence of T790M mutation. 85 (43.8%) patients harbored EGFR exon 21 L858R mutation. After 5 weeks of treatment, the initial response was assessed. No significant difference was observed in initial response between the high and low groups ( P = 0.502). The difference in best response to EGFR-TKIs between the groups was not significant ( P = 0.557). Objective response rate (ORR) was 56.2% and 57.5% respectively. There was no significant difference in median PFS [11.2 (95% CI,10.0 -12.3) vs 12.4 (95% CI,10.3-14.5) months, P = 0.509] between the groups. The high group was not significantly superior to the low group in median OS[20.5 (95% CI,18.0-23.0) vs 23.1 (95% CI,19.3-27.0) months, P = 0.500]. Conclusions: EGFR mutant allele frequency tested by NGS is not associated with the efficacy of EGFR TKIs in advanced NSCLC.

e20626 Background: Resistance mechanisms to osimertinib have raised growing concerns, but those with acquired RET rearrangement is poorly characterized. Methods: We retrospectively identified advanced, EGFR-mutant NSCLC (non-small-cell lung cancer) patients treated with osimertinib between April 9th, 2015 and November 1st, 2018 at our institute. Clinicopathologic features and clinical outcomes were analyzed. Subsequent genetic profiling was performed at the time of progression by next-generation sequencing (NGS). Overall survival (OS) since 1st line treatment was calculated from first-line treatment start to death or last follow up, and OS post-progression was calculated from osimertinib progression. Median follow-up time was 43.4 months. Results: In the 192 patients treated with osimertinib, 57 had follow-up NGS information after progression, and six harboured acquired RET rearrangement (11%, 6/57). For patients with RET rearrangements when progressed on osimertinib, OS since 1st line treatment (22.9m vs 59.5m, P = 0.021) and OS post-progression (2.1m vs 10.0m, P = 0.031) were significantly shorter compared with non- RET-rearranged cases, whereas no significant difference was found in demographics at the initial lung cancer diagnosis or progression-free survival (PFS) of osimertinib (12.1m vs 5.8m, P = 0.34). Among these six patients, one received best supportive care, two continued to use drugs targeting EGFR but deteriorating soon, three patients tried osimertinib combined with cabozantinib with one benefit from this combination approach. Conclusions: RET rearrangements could exist in EGFR-mutant NSCLC with acquired resistance to osimertinib and linked to inferior survival. Study on the molecular evolution and heterogeneity during treatment course are warranted for further therapeutic strategies. [Table: see text]