American Association for Cancer Research
ccr-23-2317_supplementary_figure_s2_suppfs2.pptx (1.36 MB)

Supplementary Figure S2 from Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma

Download (1.36 MB)
posted on 2024-01-17, 08:20 authored by Santosh Kesari, Naveed Wagle, Jose A. Carrillo, Akanksha Sharma, Minhdan Nguyen, Judy Truong, Jaya M. Gill, Raffi Nersesian, Natsuko Nomura, Elnaz Rahbarlayegh, Garni Barkhoudarian, Walavan Sivakumar, Daniel F. Kelly, Howard Krauss, Matias A. Bustos, Dave S.B. Hoon, Lars Anker, Arun S. Singh, Kamalesh K. Sankhala, Tiffany M. Juarez

Supplementary Figure S2. MRI and CT images of patient P04 with metastatic spinal chordoma in C-spine and lung. C-spine MRI before treatment (A-B) shows C-spine disease (arrows) and 12 months after initiation of high-dose pemetrexed (D-E) shows shrinkage of enhancing tumor on sagittal post contrast T1 sequences (A, D), sagittal T2 (B, E). Chest CT before treatment (C) showed multiple small metastases at baseline axial post contrast sequences that resolved after treatment (F).


Chordoma Foundation



Chordomas are ultrarare tumors of the axial spine and skull-base without approved systemic therapy. Most chordomas have negative expression of thymidylate synthase (TS), suggesting a potential for responding to the antifolate agent pemetrexed, which inhibits TS and other enzymes involved in nucleotide biosynthesis. We evaluated the therapeutic activity and safety of high-dose pemetrexed in progressive chordoma. Adult patients with previously treated, progressive chordoma participated in an open-label, single-institution, single-arm, pilot clinical trial of intravenous pemetrexed 900 mg/m2 every 3 weeks and supportive medications of folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate according to RECIST v1.1. Secondary endpoints included adverse events, progression-free survival (PFS), tumor molecular profiles, and alterations in tissue and blood-based biomarkers. Fifteen patients were enrolled and the median number of doses administered was 15 (range, 4–31). One patient discontinued treatment due to psychosocial issues after four cycles and one contracted COVID-19 after 13 cycles. Of the 14 response-evaluable patients, 2 (14%) achieved a partial response and 10 (71%) demonstrated stable disease. Median PFS was 10.5 months (95% confidence interval: 9 months–undetermined) and 6-month PFS was 67%. Adverse events were expected and relatively mild, with one grade 3 creatinine increased, and one each of grade 3 and 4 lymphopenia. No grade 5 adverse events, unexpected toxicities, or dose-limiting toxicities were observed. Several patients reported clinical improvement in disease-related symptoms. High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.

Usage metrics

    Clinical Cancer Research



    Ref. manager