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Ivosidenib Safe, Active in Patients With Advanced Chondrosarcoma
In an open-label study of patients with chondrosarcoma, ivosidenib therapy yielded limited toxicity, substantial 2-HG reduction, and durable disease control (J Clin Oncol. 2020 Mar 24. Epub ahead of print).
“Surgery is the primary therapy for localized chondrosarcoma; for locally advanced and/or metastatic disease, no known effective systemic therapy exists,” explained William D. Tap, MD, Memorial Sloan Kettering Cancer Center, New York, and colleagues.
“[Ivosidenib] is a selective inhibitor of mutant IDH1 approved in the United States for specific cases of acute myeloid leukemia,” they continued.
Thus, Dr Tap et al conducted a phase 1, multi-center clinical trial evaluating the use of ivosidenib monotherapy in 21 patients (median age, 55 years) with mutant IDH1 advanced chondrosarcoma.
These patients, 12 and 9 of whom were included in dose-escalation and expansion portions of the study, respectively, received ivosidenib 100 mg twice daily to 1200 mg once daily in continuous 28-day cycles. RECIST (v1.1) was used to assess responses every other cycle.
Treatment-emergent adverse events (AEs) were mostly grade 1 or 2, and among 12 patients who had grade ≥3 AEs, only 1 (ie, hypophosphatemia) was deemed treatment-related. Notably, all patients had substantial reductions in plasma 2-HG levels (range, 14%-94.2%) compared with those observed in healthy individuals.
The median progression-free survival rate was 5.6 months (95% CI, 1.9-7.4 months), and the 6-month PFS rate was 39.5%. Stable disease was reported in 11 (52%) patients.
“In patients with chondrosarcoma, ivosidenib showed minimal toxicity, substantial 2-HG reduction, and durable disease control,” Dr Tap and colleagues concluded.
“Future studies of ivosidenib monotherapy or rational combination approaches should be considered in patients with advanced mutant IDH1 chondrosarcoma,” they added.—Hina M. Porcelli
