49P EGFR exon 20 insertion mutations in patients with locally advanced or metastatic NSCLC in the German prospective, CRISP Registry real-world cohort (AIO-TRK-0315)

Abstract

Unlike classic/common activating mutations (mut) in the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC), low frequency exon 20 insertions (Exon20ins) exhibit inherent resistance to EGFR tyrosine kinase inhibitors (TKI) and correlate with a poor prognosis. As real-world data on these uncommon mut are rare, we show patients’ (pts) characteristics, treatment, and outcome in a representative advanced NSCLC (stage IIIB/C, IV) cohort with EGFR exon20ins mut in Germany. Pts with advanced NSCLC and EGFR exon20ins mut were identified among 5603 pts recruited into the prospective, multicenter, observational registry CRISP (NCT02622581) from December 2015 to June 2020 in Germany. We analyzed details on testing methodologies, pts’ characteristics, treatment and effectiveness by examining response, overall survival (OS), and progression-free survival (PFS). Of 5212 evaluable pts, 3448 pts were tested for EGFR mut at 1st-line treatment, 483 pts had a documented mut, including 24 pts with Exon20ins. Half of pts with Exon20ins mut were male, median age was 59 years. ECOG PS was 0 in 38%, brain metastases occurred in 17% of pts. Most pts (75%) received platin-based combination chemotherapy (ctx) ± pembrolizumab in 1st-line. Pts with platin-based 1st-line who had started 2nd-line at time of analysis (n=8) received non-platin mono ctx (n=2), checkpoint inhibitor ± ctx (n=4) or other therapies (n=2). Median PFS and OS from start of 1st-line were 8.4 [95%CI, 4.3, na] and 26.2 [95%CI, 10.2, na] months (mo) for the 24 pts with EGFR exon20ins mut at the time of database cut. Outcome was better for pts with known common (n=290) vs uncommon (n=98) EGFR mut (median PFS and OS of 14.0 [95%CI, 11.8, 17.2] and 27.2 [95%CI, 22.1, 32.5] mo vs 5.9 [95%CI, 4.4, 7.3] and 15.5 [95%CI, 10.5, 22.3] mo). These representative, prospectively collected real-world data on pts with advanced NSCLC and EGFR exon20ins mut provide insight into pts’ characteristics and current treatment patterns and may serve as an important historical control for single arm clinical trials on the therapy and outcome of this subgroup of pts.