Activity of erlotinib in patients (pts) with advanced chordoma: A retrospective study.

11528 Background: Chordoma is a rare tumor with no approved therapy. Preclinical studies have shown expression of EGFR and activated EGFR family kinases (EGFR, HER2 and HER4). Erlotinib and other anti-EGFR agents (gefitinib and cetuximab) have shown clinical activity in advanced chordoma in single case reports or small series. We aimed to evaluate the activity of erlotinib in a larger, homogeneous series of pts with advanced chordoma. Methods: We retrospectively reviewed the electronic medical records of consecutive adult pts with advanced chordoma progressive over 6 months (+/- 2 weeks, according to RECIST 1.1), treated with erlotinib (150 mg daily) at Gustave Roussy (Villejuif, France) following multidisciplinary tumor board discussion, from January 2010 to January 2021. All cases were confirmed by an expert pathologist. Response was evaluated according to RECIST 1.1, and survival was estimated using the Kaplan-Meier method. Results: Thirty-one pts [median age : 60 years (range : 32-88), median PS : 2 (range : 1-3), 30 males)] were identified. Twenty-seven (87%) had locally advanced disease; the median number of metastatic sites was 1 (range : 1-2) in the remaining 4 pts. Primary tumor site was sacral (25), lumbar (3) or cervical (3). All pts but 6 had undergone prior surgery, and 29 (94%) had undergone radiotherapy of the primary tumor. Eight pts had received previous systemic treatments (imatinib in 4, sorafenib and regorafenib in 2 each). Best tumor response by RECIST 1.1 was PR (4 pts, 13%), SD (14 pts, 45%) or PD (13 pts, 42%). Median PFS was 6.2 months (95%CI : 4.5-9.8), and median OS was 15.9 months (95%CI : 10.6-20.2). Fourteen pts (45%) remained progression-free after 1 year, and three (10%) after two years under erlotinib. Grade 3 diarrhea occurred in 4 pts (13%) and grade 3 skin rash in 13 pts (42%). Twelve pts (39%) required dose reduction to 100 mg daily due to multiple grade 2 toxicities. Ongoing studies are exploring whether candidate biomarkers such as EGFR and HER2 expression or amplification, and their mutational status could help predicting the benefit of erlotinib in pts with advanced chordoma. Conclusions: Erlotinib has clinically meaningful but unpredictable activity in advanced chordoma. Molecular profiling would probably be of high interest in this setting. This series may serve as a benchmark for future clinical trials in chordoma.