Lapatinib in advanced chordoma: A phase II study.

Abstract

10026 Background: To report on a prospective Phase II, investigator-driven, collaborative study to explore the activity of lapatinib, a dual EGFR and ErbB2 inhibitor, in EGFR-positive advanced chordomas. Methods: From December 2009 to December 2011, 19 advanced progressing chordoma patients entered this study (mean age: 59 yrs – range = 35-75; PS: 0-3 - ≥2 = 52%; site: sacrum = 68%, spine = 21%, skull base = 11%; disease extent: metastatic = 68%, locally advanced = 32%). EGFR expression was evaluated by immunohistochemistry in all patients. EGFR activation was detected in 15 of 17 evaluable cases by phospho-arrays and/or real-time PCR and/or fluorescence immunostaining. EGFR FISH analysis showed high level of gene gain in 4. HerB2 status is under evaluation. Patients received lapatinib 1500 mg/day (dose intensity in excess of 1250 mg/day), until progression or toxicity. The primary study end-point was response rate (RR) as for Choi criteria extended to MRI. Secondary end-points were RR by RECIST, PFS by Choi, OS, clinical benefit rate (CBR) (CR+PR+SD≥6mos), correlation between EGFR status and response. Results: 16 pts are evaluable for response (3 too early); 4 patients are still on treatment. 3 patients (19%) had a partial response (PR) and 8 (50%) a stable disease (SD) as their best Choi response, corresponding to RECIST SD in all cases. The 3 cases with a PR by Choi had a minor decrease in size; another patient had a mixed response. The CBR was 19%. Median PFS as for Choi was 5.5 (range = 2-12+) months, with 1 patient being progression-free at 18 months. Toxicity was as expected. In one case treatment was interrupted due to side effects. No correlation was observed between EGFR expression/activation and response. Conclusions: This Phase II study showed a modest activity of lapatinib in chordoma. EGFR expression was not predictive of response. The clinical relevance of EGFR targeting in chordoma needs to be further investigated.