Weekly cisplatin with or without imatinib in advanced chordoma: A retrospective case‐series analysis from the Italian Rare Cancers Network

Abstract

Background To report on a retrospective case‐series analysis of weekly cisplatin (wCDDP) as a single agent or combined with imatinib (wCDDP/I) in patients with advanced chordoma treated within the Italian Rare Cancer Network. Methods Adult patients with a diagnosis of advanced, brachyury‐positive chordoma, treated from April 2007 to October 2020 with wCDDP or wCDDP/I were retrospectively identified. Imatinib was withheld at the same time as wCDDP. Response according to Response Evaluation Criteria in Solid Tumors, overall survival (OS), and progression‐free survival (PFS) were analyzed. Results Thirty‐three consecutive patients were identified (wCDDP as front‐line n = 8 [24.2%]; wCDDP as a further line n = 25 [75.8%]; prior imatinib n = 25 [75.8%]; evidence of progression before starting wCDDP n = 33). Of 32 patients evaluable for response (wCDDP, n = 22 [68.8%]; wCDDP/I, n = 10 [31.3%]), best response was stable disease (SD) in 27 patients (84.3%) and progression in 5 patients (15.6%). At a median follow‐up of 54 months, the median OS (m‐OS) was 30.3 months (interquartile range [IQR], 18.1‐56.6), the m‐PFS was 8.0 months (IQR, 5.1‐17.0), the 6‐month PFS rate was 65.2%, and the 12‐month PFS rate was 30.3%. Of 22 patients who received wCDDP, the best response was SD in 18 patients (81.8%) and progression in 4 patients (18.2%), and the m‐PFS was 8.0 months (IQR, 5.1‐17.0 months). Of 10 patients who received treatment with wCDDP/I, the best response was SD in 9 patients (90%) and progression in 1 patient (10%), and the m‐PFS was 9.3 months (IQR, 4.9‐26.5 months). Conclusions This series suggests that wCDDP, both as a single agent and combined with imatinib, has antitumor activity in chordoma. Although no dimensional responses were observed, 65% and 30% of previously progressive patients were progression‐free at 6 and 12 months, respectively. A prospective study is warranted.

EP300 through upregulating the expression of vimentin to promote the progression of chordoma

“…42 Standard anthracycline chemotherapy is effective in soft-tissue tumors and osteosarcoma but exhibits limited efficacy in chordoma, 8 and cisplatin has been utilized to treat chordoma on the basis of the findings of limited retrospective series and case reports. 43 Moreover, research indicates the involvement of EP300 and vimentin in drug resistance across various tumor cells, [44][45][46][47][48] leading to the development of targeted inhibitors. This identifies them as potential targets for overcoming chemoresistance in tumor treatment.…”

Targeted therapy, immunotherapy, and chemotherapy for chordoma

“…NCCN guidelines recommend that targeted therapy can be used for the systemic treatment of chordoma. Imatinib (Adenis et al 2013;Baldi et al 2022;Hindi et al 2015;Stacchiotti et al 2009Stacchiotti et al , 2018, dasatinib (Verma et al 2020), sorafenib (Schuetze et al 2017;Bompas et al 2015), sunitinib, and lapatinib (Lebellec et al 2016a) have shown significant clinical efficacy. Thalidomide (Stacchiotti et al 2013;Chay et al 2011;Rehlinghaus et al 2012) is effective for drug-resistant chordomas, but severe toxicity limits its clinical application.…”